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The article discusses possible gene roles in pediatric high-hyperdiploid acute lymphoblastic leukemia. Topics covered include cAMP-response element binding protein-binding protein (CREBBP), and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation presence in diagnostic and relapse samples, respectively, and the deoxyribonucleic acid (DNA) mismatch repair deficiency via MutS homolog 2 (MSH2) deletion. Also noted is the better treatment of such conditions if identified early.

Background: According to current guidelines, more than 70% of patients with invasive submucosal colorectal cancer (T1 CRC) undergo a radical operation with lymph node dissection, even though only ~ 10% have lymph node metastasis (LNM). Hence, there is imperative to develop biomarkers that can help robustly identify LNM-positive patients to prevent such overtreatments. Given the emerging interest in exosomal cargo as a source for biomarker development in cancer, we examined the potential of exosomal miRNAs as LNM prediction biomarkers in T1 CRC. Methods: We analyzed 200 patients with high-risk T1 CRC from two independent cohorts, including a training (n = 58) and a validation cohort (n = 142). Cell-free and exosomal RNAs from pre-operative serum were extracted, followed by quantitative reverse-transcription polymerase chain reactions for a panel of miRNAs. Results: A panel of four miRNAs (miR-181b, miR-193b, miR-195, and miR-411) exhibited robust ability for detecting LNM in the exosomal vs. cell-free component. We subsequently established a cell-free and exosomal combination signature, successfully validated in two independent clinical cohorts (AUC, 0.84; 95% CI 0.70–0.98). Finally, we developed a risk-stratification model by including key pathological features, which reduced the false positive rates for LNM by 76% without missing any true LNM-positive patients. Conclusions: Our novel exosomal miRNA-based liquid biopsy signature robustly identifies T1 CRC patients at risk of LNM in a preoperative setting. This could be clinically transformative in reducing the significant overtreatment burden of this malignancy. [ABSTRACT FROM AUTHOR]

Background: During esophagectomy, evaluation of blood supply to the gastric tube is critically important to estimate and avoid anastomotic complications. This retrospective study investigated the relationship between indocyanine green (ICG) fluorescence angiography during esophagectomy and postoperative endoscopy findings, especially mucosal color change. Methods: This study retrospectively collected data from 86 patients who underwent subtotal esophagectomy and reconstruction using a gastric tube for esophageal cancer at the Tokyo Medical and Dental University between 2017 and 2020. The flow speed of ICG fluorescence in the gastric tube was evaluated during the operation. Additionally, the main root of ICG enhancement and pattern of ICG distribution in the gastric tube were evaluated. On postoperative day 1 (POD1), the change in the mucosal color to white, thought to reflect ischemia, or black, thought to reflect congestion of the proximal gastric tube, was evaluated. The correlations between these factors, clinical parameters, and surgical outcomes were evaluated. Univariate and multivariate analyses used logistic regression to identify the risk factors affecting mucosal color change. Results: Multivariate analyses revealed that the only independent significant predictor of mucosal congestion on POD1 was the ICG enhancement time of the right gastric tube tip (odds ratio, 14.49; 95% confidential interval, 2.41–87.24; P = 0.004). Conclusions: This study indicated that the ICG enhancement time is related to venous malperfusion and congestion rather than arterial malperfusion and ischemia. [ABSTRACT FROM AUTHOR]

Anemia and iron deficiency (ID) are common in patients with heart failure (HF) and intravenous (IV) administration of iron to patients hospitalized for decompensated HF with ID improves outcome. The diagnosis of ID in routine practice is based on serum ferritin and transferrin saturation (TSAT) but both have limitations; alternatives should be considered. Reticulocyte hemoglobin equivalent (Ret-He) reflects iron content in reticulocytes but its clinical utility in patients with HF remains uncertain. We prospectively enrolled 142 patients hospitalized for decompensated HF. Sixty five percent had ID as defined in current international guidelines. Ret-He was directly correlated with serum iron and ferritin concentrations and with TSAT. There was a poor relationship between quartile of Ret-He and HF hospitalization or death but increases or decreases in Ret-He between admission and discharge were associated with a worse outcome. The clinical utility of Ret-He for identifying ID and predicting response to IV iron and prognosis for patients with HF requires further investigation. [ABSTRACT FROM AUTHOR]

It has been postulated from a combination of evidence that a sudden increase in COVID-19 cases among pediatric patients after onset of the Omicron wave was attributed to a reduced requirement for TMPRSS2-mediated entry in pediatric airways with lower expression levels of TMPRSS2. Epidemic strains were isolated from the indigenous population in an area, and the levels of TMPRSS2 required for Delta and Omicron variants were assessed. As a result, Delta variants proliferated fully in cultures of TMPRSS2-positive Vero cells but not in TMPRSS2-negative Vero cell culture (350-fold, Delta vs 9.6-fold, Omicron). There was no obvious age-dependent selection of Omicron strains affected by the TMPRSS2 (9.6-fold, Adults vs. 12-fold, Children). A phylogenetic tree was generated and Blast searches (up to 100 references) for the spread of strains in the study area showed that each strain had almost identical homology (>99.5%) with foreign isolates, although indigenous strains had obvious differences from each other. This suggested that the differences had been present abroad for a long period. Therefore, the lower requirement for TMPRSS2 by Omicron strains might be applicable to epidemic strains globally. In conclusion, the property of TMPRSS2-independent cleavage makes Omicron proliferate with ease and allows epidemics among children with fewer TMPRSS2 on epithelial surfaces of the respiratory organs. [ABSTRACT FROM AUTHOR]

Limb ischemia (LI) is a major consequence of peripheral artery disease (PAD) with a high mortality rate. Iron is an essential mineral to maintain physiological function of multiple organs. Intracellular iron transport is regulated by transferrin receptor 1 (TfR1). Although increase in serum ferritin levels has been reported in PAD patients, the mechanism of iron metabolism in LI is still unclear. The aim of this study is to investigate whether TfR1 deletion attenuates LI formation. To generate LI, the left femoral artery of 8–10 week-old C57BL6/J male mice was ligated. Adductor muscles were harvested at 28 days after surgery to investigate iron metabolism. The level of ferritin, intracellular iron storage protein, was higher in ischemic adductor muscles compared to non-ischemic adductor muscles. Level of intracellular iron transport protein, TfR1, was decreased in ischemic adductor muscles. LI was then generated in TfR1 heterozygous deleted mice (TfR1+/−) to examine whether TfR1 contributes to the pathophysiology of LI. Laser Doppler blood flowmetry revealed that blood flow recovery was attenuated in TfR1+/− mice compared to wild type (WT) littermates, along with decreased expression of ferritin and CD31 in ischemic adductor muscles. Since iron is used for energy production in mitochondria, we then assessed mitochondrial complexes in the ischemic adductor muscle. Of interest, expression of mitochondrial complex I, but not complexes II, III, and V in ischemic adductor muscles was significantly reduced in TfR1+/− mice compared to WT mice. Haploinsufficiency of TfR1 attenuated angiogenesis via reduction of mitochondrial complex I in LI in mice. [ABSTRACT FROM AUTHOR]

Background: Mechanistic target of rapamycin (mTOR) pathway is essential for the growth of gastric cancer (GC), but mTOR inhibitor everolimus was not effective for the treatment of GCs. The Cancer Genome Atlas (TCGA) researchers reported that most diffuse-type GCs were genomically stable (GS). Pathological analysis suggested that some diffuse-type GCs developed from intestinal-type GCs. Methods: We established patient-derived xenograft (PDX) lines from diffuse-type GCs, and searched for drugs that suppressed their growth. Diffuse-type GCs were classified into subtypes by their gene expression profiles. Results: mTOR inhibitor temsirolimus strongly suppressed the growth of PDX-derived diffuse-type GC-initiating cells, which was regulated via Wnt-mTOR axis. These cells were microsatellite unstable (MSI) or chromosomally unstable (CIN), inconsistent with TCGA report. Diffuse-type GCs in TCGA cohort could be classified into two clusters, and GS subtype was major in cluster I while CIN and MSI subtypes were predominant in cluster II where PDX-derived diffuse-type GC cells were included. We estimated that about 9 and 55% of the diffuse-type GCs in cluster II were responders to mTOR inhibitors and checkpoint inhibitors, respectively, by identifying PIK3CA mutations and MSI condition in TCGA cohort. These ratios were far greater than those of diffuse-type GCs in cluster I or intestinal-type GCs. Further analysis suggested that diffuse-type GCs in cluster II developed from intestinal-type GCs while those in cluster I from normal gastric epithelial cells. Conclusion: mTOR inhibitors and checkpoint inhibitors might be useful for the treatment of a subset of diffuse-type GCs which may develop from intestinal-type GCs. [ABSTRACT FROM AUTHOR]

Introduction: Anemia and chronic kidney disease (CKD) are common comorbidities in patients with heart failure (HF), especially patients with HF with preserved left ventricular fraction (HFpEF). However, little is known about the impact of anemia on prognosis in HFpEF patients with CKD. Hypothesis: In this study, we investigated the impact of anemia on prognosis in HFpEF patients with CKD enrolled in Japanese heart failure syndrome with preserved ejection fraction (JASPER) registry. Methods: We examined 535 consecutive HFpEF patients (mean age: 78 ± 11 years) enrolled in JASPER registry. CKD was defined as an estimated glomerular filtration rate (eGFR) of <60ml/min/1.73m2. Anemia was defined according to the WHO criteria. Results: The prevalence rate of CKD is 69% in all groups studied. HFpEF patients with CKD were older, lower heart rate, and higher prevalence of hypertension, past hospitalization of HF, and old myocardial infarction compared with HFpEF patients without CKD. The prevalence rate of anemia was 83% and mean blood hemoglobin (Hb) levels were 10.7 g/dL in HFpEF patients with CKD. Blood Hb levels were positively correlated with eGFR in HFpEF patients with CKD but not in without CKD. Kaplan-Meier analysis for all-cause death and HF re-admission demonstrated that anemic patients had poor prognosis compared with non-anemic patients in HFpEF patients with CKD (47% vs. 28%, p=0.003). Meanwhile, concerned with HFpEF patients without CKD, all-cause death and HF re-admission were not statistically different between anemic and non-anemic patients (34% vs. 36%, p=0.522). In addition, Cox proportional hazards regression analysis showed that only blood Hb levels (HR 0.80; 95% confidence interval [CI] 0.70 to 0.91; p<0.001) were an independent predictor for all-cause death and HF re-admission in HFpEF patients with CKD. Survival CART analysis showed that blood Hb levels of 8.7 g/dL for HFpEF patients with CKD were more accurate cut-off value predicting all-cause death and HF re-admission. Conclusions: Anemia was a critical factor determining prognosis in HFpEF patients with CKD. In addition, blood Hb levels were an independent predictor of all-cause death and HF re-admission in HFpEF patients with CKD. [ABSTRACT FROM AUTHOR]

Introduction: Anemia and atrial fibrillation (AF) are common comorbidities in patients with heart failure preserved left ventricular ejection fraction (HFpEF). Moreover, both anemia and AF worsen prognosis in HFpEF patients. However, little is known about the association of anemia and AF with prognosis in HFpEF patients. Hypothesis: Here, we investigated the association between anemia, AF, and prognosis in HFpEF patients enrolled in Japanese heart failure syndrome with preserved ejection fraction (JASPER) registry. Methods: 529 consecutive HFpEF patients (mean age: 78 ± 11 years) were enrolled in JASPER registry. Anemia was defined according to the World Health Organization criteria. The cumulative incidence of all-cause mortality and heart failure (HF) re-admission was evaluated by the Kaplan-Meier analysis. Associations between patient characteristics and clinical outcomes were assessed by Cox proportional hazards regression analysis. Results: The prevalence rate of AF was 62% in all groups studied. HFpEF patients with AF were older (79 ± 9.1 vs. 76 ± 13 years, p=0.01), lower systolic blood pressure (146 ± 31 vs. 160 ± 42 mmHg, p<0.001), and higher heart rate (87 ± 29 vs. 82 ± 28 beats/min, p<0.05) compared with HFpEF patients without AF. HFpEF patients with AF had higher prevalence of past hospitalization of HF (45.0 % vs. 26.0 %, p<0.001) and cerebrovascular disease (27.0% vs. 18.0%, p=0.013). Anemia was complicated with 72.3% in HFpEF patients with AF and 71.5% in HFpEF patients without AF. Kaplan-Meier analysis for all-cause mortality and HF re-admission demonstrated that anemic patients had poor prognosis compared with non-anemic patients in both HFpEF patients with and without AF (42 % vs. 27 %, p=0.024 and 36 % vs. 14 %, p=0.005, respectively). However, unexpectedly, multivariate analysis showed that anemia was an independent predictor for all-cause mortality and HF re-admission in only HFpEF patients without AF (HR 2.60; 95% confidence interval [CI] 1.05 to 6.45; p<0.04). Of interest, survival CART analysis demonstrated that blood Hb level of 11.5 g/dL for HFpEF patients without AF was more accurate cut-off value predicting all-cause death and HF re-admission. Conclusions: Anemia is an independent predictor of all-cause mortality and HF re-admission in HFpEF patients without AF. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of anemia is higher in heart failure with preserved left ventricular ejection fraction (HFpEF) than in heart failure with reduced left ventricular ejection fraction. However, little is known about the association of anemia and gender with prognosis in HFpEF patients. Hypothesis: In this study, we investigated the association between anemia, gender, and prognosis in HFpEF patients. We also assessed effective blood hemoglobin (Hb) level in HFpEF patients. Methods: We examined 535 consecutive HFpEF patients (mean age: 78 ± 11 years) in Japanese heart failure syndrome with preserved ejection fraction (JASPER) registry. The cumulative incidence of all-cause mortality and heart failure (HF) re-admission was evaluated by the Kaplan-Meier analysis. Associations between patient characteristics and clinical outcomes were assessed by Cox proportional hazards regression analysis. Results: According to the World Health Organization criteria, the prevalence rate of anemia was 74% in male patients and 70% in female patients. Kaplan-Meier analysis for all-cause mortality demonstrated that anemic patients had poor prognosis compared with non-anemic patients in both male and female HFpEF patients (26.8% vs. 11.2%, p=0.030 and 22.5% vs. 5.8%, p=0.006, respectively). Meanwhile, HF re-admission rate were not statistically different between two groups in both male and female HFpEF patients (27.5% vs. 21.9%, p=0169 and 34.3% vs. 32.7%, p=0.102, respectively). Interestingly, multivariate analysis revealed that only blood Hb level was an independent predictor of all-cause mortality in both male and female HFpEF patients. According to survival classification and regression tree analysis, blood Hb level of 9.4g/dL for male and 12.3g/dL for female were more accurate cut-off value predicting all-cause mortality in HFpEF patients. Conclusions: Althogh blood Hb level is an independent predictor of all-cause death in both male and female HFpEF patients, effective blood Hb level for the prevention of all-cause mortality is different between male and female HFpEF patients. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is one of the leading causes of cancer deaths, and gastrectomy with lymph node dissection is the mainstay of treatment. Despite clinician efforts and advances in surgical methods, the incidence of complications after gastrectomy remains 10%–20% including fatalities. To the best of our knowledge, this is the first report on utilization of a deep learning method to build a new artificial intelligence model that could help surgeons diagnose these complications. Methods: A neural network was constructed with a total of 4000 variables. Clinical, surgical, and pathological data of patients who underwent radical gastrectomy at our institute were collected to maintain a deep learning model. We optimized the parameters of the neural network to diagnose whether these patients would develop complications after gastrectomy or not. Results: Seventy percent of the data was used to optimize the neural network parameters, and the rest was used to validate the model. A model that maximized the receiver operating characteristics (ROC) area under the curve (AUC) for validation of the data was extracted. The ROC‐AUC, sensitivity, and specificity of the model to diagnose all complications were 0.8 vs 0.7, 81% vs 50%, and 69% vs 75%, for the teaching and validation data, respectively. Conclusions: A predictive model for postoperative complications after radical gastrectomy was successfully constructed using the deep learning method. This model can help surgeons accurately predict the incidence of complications on postoperative day 3. [ABSTRACT FROM AUTHOR]

Purpose: We are attempting to develop a navigation system for safe and effective peripancreatic lymphadenectomy in gastric cancer surgery. As a preliminary study, we examined whether or not the peripancreatic dissection line could be learned by a machine learning model (MLM). Methods: Among the 41 patients with gastric cancer who underwent radical gastrectomy between April 2019 and January 2020, we selected 6 in whom the pancreatic contour was relatively easy to trace. The pancreatic contour was annotated by a trainer surgeon in 1242 images captured from the video recordings. The MLM was trained using the annotated images from five of the six patients. The pancreatic contour was then segmented by the trained MLM using images from the remaining patient. The same procedure was repeated for all six combinations. Results: The median maximum intersection over union of each image was 0.708, which was higher than the threshold (0.5). However, the pancreatic contour was misidentified in parts where fatty tissue or thin vessels overlaid the pancreas in some cases. Conclusion: The contour of the pancreas could be traced relatively well using the trained MLM. Further investigations and training of the system are needed to develop a practical navigation system. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether muscle synergy differs between swimmers with and without swimmer's shoulder in the butterfly technique. Muscle synergies, which can assess muscle coordination, were analyzed using surface electromyography. Twenty elite swimmers were included in this study (swimmer's shoulder: n = 8; control: n = 12). The motions involved in executing the butterfly technique were classified into the early pull-through, late pull-through, and recovery phases. Muscle synergy data analyzed using the nonnegative matrix factorization method were compared between the two groups. The swimming velocities were 1.66 ± 0.09 m・s −1 and 1.69 ± 0.06 m・s −1 for the control and swimmer's shoulder groups, respectively. Four muscle synergies in both groups were identified: synergy #1, which was involved in the early pull; synergy #2, involved in the late pull; synergy #3, involved in the early recovery; and synergy #4, involved in pre- and posthand entry. Compared to the control group, the swimmer's shoulder group had a small contribution from the pectoralis major (p = 0.032) and a high contribution from the rectus femoris during the early pull phase (p = 0.036). In the late pull phase, the contribution of the lower trapezius muscle in the swimmer's shoulder group was low (p = 0.033), while the contribution of the upper trapezius muscle in the pre- and postentry phases was high (p = 0.032). In the rehabilitation of athletes with swimmer's shoulder, it is therefore important to introduce targeted muscle rehabilitation in each phase. [ABSTRACT FROM AUTHOR]

Background: Anastomotic stricture is a relatively common postoperative complication after esophagectomy. Previous studies have indicated that impaired perioperative blood perfusion at the anastomosis is associated with the occurrence of stricture. Therefore, we analyzed the association between endoscopically assessed blood perfusion during the early postoperative period and anastomotic stricture. Methods: This retrospective study evaluated patients who underwent esophagectomy at Tokyo Medical and Dental University between 2010 and 2015. The patients had undergone nasal endoscopy on the 1st and 8th postoperative days. The findings were used to evaluate blood perfusion at the anastomosis and gastric tube, which was classified based on mucosal color as ischemia (white) or congestion (blue or black). Univariate and multivariable logistic regression analyses were performed to identify risk factors for anastomotic stricture. Results: The study included 197 patients and anastomotic stricture was observed in 60 patients (30.4%). The multivariable analysis revealed that postoperative gastric tube congestion was a risk factor for stricture (odds ratio [OR]: 6.440, 95% confidence interval [CI]: 2.660–15.600; p < 0.001). Lower risks of anastomotic stricture were associated with pathological stage III–IV disease (OR: 0.325, 95% CI: 0.161–0.656; p = 0.002). Conclusion: This study revealed that endoscopically detected congestion at the anastomosis on the first postoperative day was a risk factor for anastomotic stricture. [ABSTRACT FROM AUTHOR]

Background: Although many methods to prevent the development of postoperative pancreatic fistula (POPF) after gastrectomy have been reported, POPF can only be identified after it has occurred. Various therapeutic measures could be taken if signs of POPF could be detected intraoperatively. Methods: We conducted a prospective study in which we attempted to predict POPF by measuring the intraoperative amylase concentration in the peripancreatic body fluid. To collect the body fluid, three sponges were placed around the pancreas at lymph node station Nos. 6, 8, and 11 during lymphadenectomy. The amylase concentration was measured in the body fluid squeezed from the sponges. We investigated whether the intraoperative body fluid amylase concentration (IBAC) was associated with POPF formation. Results: In total, 109 patients were enrolled from February 2016 to March 2018, and we analyzed 81 eligible patients. Clavien–Dindo grade ≥ II POPF occurred in eight patients (9%). The IBAC was significantly higher in sponges No. 6 (P = 0.044) and No. 8 (P = 0.007). The incidence of POPF was predicted by using an IBAC cutoff value for No. 6 (1047 IU/L; sensitivity 87.5%; specificity 65.0%; positive likelihood ratio 2.5) and No. 8 (400 IU/L; sensitivity 87.5%; specificity 68.5%; positive likelihood value 2.8), respectively. The IBAC in sponge No. 11 tended to be higher (P = 0.054). Conclusions: By measuring the IBAC, surgeons might predict POPF easily and noninvasively during surgery. This method is one of the most effective ways to predict POPF intraoperatively. [ABSTRACT FROM AUTHOR]

The interaction among heart failure (HF), chronic kidney disease (CKD), and anemia is called cardio-renal anemia syndrome. The mechanism of anemia in cardio-renal anemia syndrome is complex and remains completely unknown. We have previously reported that impaired intestinal iron transporters may contribute to the mechanism of anemia in HF using in vivo HF model rats. In this study, we assessed intestinal iron transporters in CKD model rats to investigate the association of intestinal iron transporters in the mechanism of cardio-renal anemia syndrome. CKD was induced by 5/6 nephrectomy in Sprague-Dawley rats. Sham-operated rats served as a control. After 24-week surgery, CKD rats exhibited normocytic normochromic anemia and normal serum erythropoietin levels despite of anemia. Serum iron levels were decreased in CKD rats compared with the controls. Of interest, intestinal expression of critical iron importers, such as duodenal cytochrome b (Dcyt-b) and divalent metal transporter 1 (DMT-1), was decreased in CKD rats compared with the controls. On the other hand, intestinal expression of ferroportin, an intestinal iron exporter, was not different in the control and CKD groups. Moreover, hepatic expression of hepcidin, a regulator of iron homeostasis, did not differ between the control and CKD groups. These results suggest that impaired intestinal expression of Dcyt-b and DMT-1 might be associated with the reduction of an iron uptake in CKD. Taken together, impaired these intestinal iron transporters may become a novel therapeutic target for cardio-renal anemia syndrome. [ABSTRACT FROM AUTHOR]

Background: Proximal gastrectomy (PG) is widely performed in Japan as a function-preserving surgical approach. Since esophagogastrostomy (EG) was associated with increased reflux symptoms and anastomotic strictures, we have chosen double-tract reconstruction (DTR) as the standard reconstruction method since March 2013. In this study, we described a novel method of laparoscopic DTR using detachable ENDO-PSD and compared its 1-year outcome with EG performed formerly in our institution.Methods: Patients who underwent laparoscopic PG between May 2005 and July 2014 were retrospectively divided into two groups based on the type of reconstruction and were subsequently analyzed (19 patients in the DTR group and 22 in the EG group). All of them underwent a laparoscopic PG with regional lymph node dissection. In the DTR group, the lower left port site was extended to 4 cm, and an intracorporeal purse-string suture was performed using the detachable ENDO-PSD. The jejunogastrostomy was fashioned on the anterior side of the remnant stomach parallel to the transection line, 2 cm from the cut end. The EG group used the conventional purse-string suture instrument through the 6 cm upper midline mini-laparotomy incision. Patient characteristics, operative data, early operative complications and 1-year postoperative follow-up findings were compared between the two groups.Results: The frequencies of reflux symptoms (10.5 vs. 54.5%, P = 0.003), usage of proton pump inhibitors (31.6 vs. 72.7%, P = 0.008), and anastomotic strictures (0 vs. 27%, P = 0.014) were significantly lower in the DTR group as compared to the EG group. There were no significant differences between the two groups with regard to operation time, blood loss, postoperative hospital stay, postoperative complications, average postoperative/preoperative weight loss ratio, and postoperative/preoperative ratio of biochemical markers (hemoglobin, total protein, albumin, cholesterol).Conclusion: Our results indicate that DTR is a useful reconstruction method after PG, especially in terms of preventing reflux esophagitis and anastomotic strictures. [ABSTRACT FROM AUTHOR]

Background: Aronia berry extracts (ABE) have recently been reported to possess significant anti-cancer effects in various malignancies, including colorectal cancer (CRC), due to their high polyphenolic content. However, the molecular mechanism(s) underlying the anti-cancer effects of ABE in CRC remain unclear, which is important to consider when considering their use as complementary medicine approaches in cancer., Methods: We performed genome-wide transcriptomic profiling and pathway enrichment analysis to identify specific growth signaling pathways associated with ABE treatment in CRC cells. In addition, a series of systematic and comprehensive cell culture studies were performed to investigate the anti-cancer effects of ABE in SW480 and HCT116 CRC cell lines. Subsequently, these findings were validated in patient-derived 3D organoids (PDOs) models., Results: Transcriptomic profiling analysis identified p53 signaling as one of the key enriched pathways mediating the anti-cancer activity of ABE. Analysis of public datasets revealed that Chk1, a key regulator of p53, was one of the critical targets of ABE in CRC. Chk1 and p53 activation was shown to be downregulated with ABE treatment, leading to the induction of cell cycle arrest (p = 0.003-0.014) and enhanced DNA damage (p = 0.015-0.026). Furthermore, these findings were validated in PDOs, where the ABE treatment resulted in significantly fewer and smaller PDOs in a concentration-dependent manner (p = 0.045 - <0.001)., Conclusions: We firstly provide evidence for the role of the p53 signaling pathway as a mediator of the anti-cancer activity of ABE, which provides a rationale for its use as a safe and effective integrative medicine approach in CRC., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Lymphadenectomy around the recurrent laryngeal nerve (RLN) is an essential part of curative surgery for esophageal cancer. Although several single-center studies have shown that intraoperative nerve monitoring (IONM) can avoid RLN palsy, this has not been confirmed in a large-scale multicenter study. This study was performed to evaluate whether IONM can reduce postoperative RLN palsy during minimally invasive esophagectomy (MIE) for esophageal cancer using a national database., Methods: We retrieved data of patients with esophageal cancer who underwent three-field MIE with cervical anastomosis involving thoracoscopic or robotic esophagectomy with IONM (502 patients) and without IONM (4,353 patients) from April 2020 to March 2022 from the Diagnosis Procedure Combination database in Japan. We compared the frequency of postoperative RLN palsy and respiratory complications between the IONM(+) group and IONM(-) group using propensity score-matching analysis., Results: The postoperative RLN palsy rate was significantly lower in the IONM(+) than (-) group (odds ratio, 0.24; 95% confidence interval [CI], 0.13-0.46). The respiratory complication rate was also significantly lower in the IONM(+) than (-) group (odds ratio, 0.66; 95%CI, 0.45-0.97). The anesthesia time was significantly longer in the IONM(+) group (regression coefficient, 60.1 minutes; 95%CI, 44.2-76.9). The length of postoperative hospitalization tended to be shorter in the IONM(+) than (-) group (regression coefficient, -1.39 days; 95%CI, -3.91 to 1.14)., Conclusions: This national cohort study showed that IONM during three-field MIE for esophageal cancer was associated with a reduction of postoperative RLN palsy and respiratory complications., (Copyright © 2024. Published by Elsevier Inc.)

When Epstein-Barr virus (EBV) infection is suspected, identification of infected cells is important to understand the pathogenesis, determinine the treatment strategy, and predict the prognosis. We used the PrimeFlow™ RNA Assay Kit with a probe to detect EBV-encoded small RNAs (EBERs) and multiple surface markers, to identify EBV-infected cells by flow cytometry. We analyzed a total of 24 patients [11 with chronic active EBV disease (CAEBV), 3 with hydroa vacciniforme lymphoproliferative disorder, 2 with X-linked lymphoproliferative disease type 1 (XLP1), 2 with EBV-associated hemophagocytic lymphohistiocytosis, and 6 with posttransplant lymphoproliferative disorder (PTLD)]. We compared infected cells using conventional quantitative PCR methods and confirmed that infected cell types were identical in most patients. Patients with CAEBV had widespread infection in T and NK cells, but a small amount of B cells were also infected, and infection in patients with XLP1 and PTLD was not limited to B cells. EBV-associated diseases are believed to be complex pathologies caused by EBV infecting a variety of cells other than B cells. We also demonstrated that infected cells were positive for HLA-DR in patients with CAEBV. EBER flow FISH can identify EBV-infected cells with high sensitivity and is useful for elucidating the pathogenesis., (© 2024. Japanese Society of Hematology.)

Objective: Although hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors have been developed for the treatment of renal anemia, their effects on cardiac and renal dysfunction remain unknown. We previously reported on Dahl salt-sensitive rats, in a rat model of salt-sensitive hypertension, that exhibited anemia and impaired expression of duodenal iron transporters after the development of hypertensive cardiac and renal dysfunction. Therefore, we investigated the effects of Roxadustat (FG-4592), an HIF-PH inhibitor, on anemia, iron regulation, and cardiac and renal dysfunction in Dahl salt-sensitive rats., Methods: Six-week-old male Dahl salt-sensitive rats were fed a normal or high-salt diet for 8 weeks. A further subset of Dahl salt-sensitive rats, that were fed a high-salt diet, was administered Roxadustat for 8 weeks., Results: Dahl salt-sensitive rats fed a high-salt diet developed hypertension, cardiac and renal dysfunction, and anemia after 8 weeks of feeding. Roxadustat increased hemoglobin and serum erythropoietin levels in Dahl salt-sensitive rats fed a high-salt diet. With regard to the iron-regulating system, Roxadustat lowered hepatic hepcidin gene expression and increased the gene expression of duodenal iron transporters, such as cytochrome b and divalent metal transporter 1 , in Dahl salt-sensitive rats fed a high-salt diet. Roxadustat did not affect the development of hypertension and cardiac hypertrophy in Dahl salt-sensitive rats with a high-salt diet; however, Roxadustat treatment attenuated renal fibrosis in these rats., Conclusions: Roxadustat ameliorated anemia with affecting the gene expression of the iron-regulating system, and did not affect cardiac hypertrophy but attenuated renal fibrosis in Dahl salt-sensitive rats fed a high-salt diet., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)