Thoracoscopic primary repair is useful for esophageal atresia with tracheoesophageal fistula in neonates with low body weight.

PURPOSE: The surgical indication of thoracoscopic primary repair for esophageal atresia with tracheoesophageal fistula is under debate. The current study aimed to investigate the outcome of thoracoscopic primary repair for esophageal atresia with tracheoesophageal fistula in patients weighing < 2000 g and those who underwent emergency surgery at the age of 0 day. METHODS: The surgical outcomes were compared between patients weighing < 2000 g and those weighing > 2000 g at surgery and between patients who underwent surgery at the age of 0 day and those who underwent surgery at age ≥ 1 day. RESULTS: In total, 43 patients underwent thoracoscopic primary repair for esophageal atresia with tracheoesophageal fistula. The surgical outcomes according to body weight were similar. Patients who underwent surgery at the age of 0 day were more likely to develop anastomotic leakage than those who underwent surgery at the age of ≥ 1 day (2 vs. 0 case, p = 0.02). Anastomotic leakage was treated with conservative therapy. CONCLUSION: Thoracoscopic primary repair is safe and useful for esophageal atresia with tracheoesophageal fistula even in newborns weighing < 2000 g. However, emergency surgery at the age of 0 day should be cautiously performed due to the risk of anastomotic leakage.

Fundamental study on diagnostic reference level quantities for endoscopic retrograde cholangiopancreatography using a C-arm fluoroscopy system.

The diagnostic reference level (DRL) is an effective tool for optimising protection in medical exposures to patients. However regarding air kerma at the patient entrance reference point (Ka,r), one of the DRL quantities for endoscopic retrograde cholangiopancreatography (ERCP), manufacturers use a variety of the International Electrotechnical Commission and their own specific definitions of the reference point. The research question for this study was whetherKa,ris appropriate as a DRL quantity for ERCP. The purpose of this study was to evaluate the difference betweenKa,rand air kerma incident on the patient's skin surface (Ka,e) at the different height of the patient couch for a C-arm system. Fluoroscopy and radiography were performed using a C-arm system (Ultimax-i, Canon Medical Systems, Japan) and a over-couch tube system (CUREVISTA Open, Fujifilm Healthcare, Japan).Ka,ewas measured by an ion chamber placed on the entrance surface of the phantom. Kerma-area product (PKA) andKa,rwere measured by a built-inPKAmeter and displayed on the fluoroscopy system.Ka,edecreased whileKa,rincreased as the patient couch moved away from the focal spot. The uncertainty of theKa,e/Ka,rratio due to the different height of the patient couch was estimated to be 75%-94%.Ka,rmay not accurately representKa,e.PKAwas a robust DRL quantity that was independent of the patient couch height. We cautioned against optimising patient doses in ERCP with DRLs set in terms ofKa,rwithout considering the patient couch height of the C-arm system. Therefore, we recommend thatKa,ris an inappropriate DRL quantity in ERCP using the C-arm system.

miR-122-5p Regulates Renal Fibrosis In Vivo.

The role of exogenous microRNAs (miRNAs) in renal fibrosis is poorly understood. Here, the effect of exogenous miRNAs on renal fibrosis was investigated using a renal fibrosis mouse model generated by unilateral ureteral obstruction (UUO). miRNA microarray analysis and quantitative reverse-transcription polymerase chain reaction showed that miR-122-5p was the most downregulated (0.28-fold) miRNA in the kidneys of UUO mice. The injection of an miR-122-5p mimic promoted renal fibrosis and upregulated COL1A2 and FN1, whereas an miR-122-5p inhibitor suppressed renal fibrosis and downregulated COL1A2 and FN1. The expression levels of fibrosis-related mRNAs, which were predicted targets of miR-122-5p, were evaluated. The expression level of TGFBR2, a pro-fibrotic mRNA, was upregulated by the miR-122-5p mimic, and the expression level of FOXO3, an anti-fibrotic mRNA, was upregulated by the miR-122-5p inhibitor. The protein expressions of TGFBR2 and FOXO3 were confirmed by immunohistochemistry. Additionally, the expression levels of LC3, downstream anti-fibrotic mRNAs of FOXO3, were upregulated by the miR-122-5p inhibitor. These results suggest that miR-122-5p has critical roles in renal fibrosis.

Lipidome-based rapid diagnosis with machine learning for detection of TGF-ß signalling activated area in head and neck cancer.

BACKGROUND: Several pro-oncogenic signals, including transforming growth factor beta (TGF-ß) signalling from tumour microenvironment, generate intratumoural phenotypic heterogeneity and result in tumour progression and treatment failure. However, the precise diagnosis for tumour areas containing subclones with cytokine-induced malignant properties remains clinically challenging. METHODS: We established a rapid diagnostic system based on the combination of probe electrospray ionisation-mass spectrometry (PESI-MS) and machine learning without the aid of immunohistological and biochemical procedures to identify tumour areas with heterogeneous TGF-ß signalling status in head and neck squamous cell carcinoma (HNSCC). A total of 240 and 90 mass spectra were obtained from TGF-ß-unstimulated and -stimulated HNSCC cells, respectively, by PESI-MS and were used for the construction of a diagnostic system based on lipidome. RESULTS: This discriminant algorithm achieved 98.79% accuracy in discrimination of TGF-ß1-stimulated cells from untreated cells. In clinical human HNSCC tissues, this approach achieved determination of tumour areas with activated TGF-ß signalling as efficiently as a conventional histopathological assessment using phosphorylated-SMAD2 staining. Furthermore, several altered peaks on mass spectra were identified as phosphatidylcholine species in TGF-ß-stimulated HNSCC cells. CONCLUSIONS: This diagnostic system combined with PESI-MS and machine learning encourages us to clinically diagnose intratumoural phenotypic heterogeneity induced by TGF-ß.

Loss of myeloid-specific lamin A/C drives lung metastasis through Gfi-1 and C/EBPε-mediated granulocytic differentiation.

The immune-suppressive tumor microenvironment promotes metastatic spread and outgrowth. One of the major contributors is tumor-associated myeloid cells. However, the molecular mechanisms regulating their differentiation and function are not well understood. Here we report lamin A/C, a nuclear lamina protein associated with chromatin remodeling, was one of the critical regulators in cellular reprogramming of tumor-associated myeloid cells. Using myeloid-specific lamin A/C knockout mice and triple-negative breast cancer (TNBC) mouse models, we discovered that the loss of lamin A/C drives CD11b+ Ly6G+ granulocytic lineage differentiation, alters the production of inflammatory chemokines, decreases host antitumor immunity, and increases metastasis. The underlying mechanisms involve an increased H3K4me3 leading to the upregulation of transcription factors (TFs) Gfi-1 and C/EBPε. Decreased lamin A/C and increased Gfi-1 and C/EBPε were also found in the granulocytic subset in the peripheral blood of human cancer patients. Our data provide a mechanistic understanding of myeloid lineage differentiation and function in the immune-suppressive microenvironment in TNBC metastasis.

Successful treatment of cholesterol crystal embolism with anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody: a case report.

Background: We report a unique case of renal cholesterol crystal embolism (CCE) induced by carotid artery stenting that was successfully treated with evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin kexin type 9 (PCSK9).Case presentation: A 77-year-old man with hypertension, hyperlipidemia, and chronic kidney disease was referred to our department for decreased estimated glomerular filtration rate (eGFR)-from 32.0 to 13.9 mL/min/1.73 m2-5 weeks after carotid artery stenting. Further examination revealed livedo reticularis in the bilateral toes and eosinophilia (723/µL). Skin biopsy from livedo reticularis tissue in the bilateral toes showed cholesterol clefts in the small arteries. The patient was therefore diagnosed with CCE. After 25 weeks' administration of evolocumab at a dose of 140 mg subcutaneously administered every 2 weeks, his eGFR had improved from 10.7 to 18.1 mL/min/1.73 m2.Conclusion: Evolocumab may have a beneficial effect on renal involvement in patients with CCE.

Association between carnitine deficiency and the erythropoietin resistance index in patients undergoing peritoneal dialysis: a cross-sectional observational study.

Carnitine deficiency contributes to developing various pathological conditions, such as cardiac dysfunction, muscle weakness, and erythropoietin-resistant anemia in patients undergoing hemodialysis. However, a conclusion has not been reached concerning the prevalence and the effect of carnitine deficiency in patients undergoing peritoneal dialysis (PD). In this study, the prevalence of carnitine deficiency and the clinical factors associated with carnitine deficiency were investigated in 60 patients undergoing PD. The median age of the patients was 62.5 years (52.5-72.5 years), the proportion of male sex was 44/60 (73.3%), and the median PD period was 24 months (12-45 months). Carnitine deficiency (acyl carnitine/free carnitine ratio >0.4) was detected in 56/60 (93%) patients. Multiple regression analysis showed that the erythropoietin resistance index was independently associated with carnitine deficiency (ß = 0.283, p = 0.04). These results suggest that carnitine plays pivotal roles in hematogenesis in patients undergoing PD.

Attenuation of Myeloid-Specific TGFß Signaling Induces Inflammatory Cerebrovascular Disease and Stroke.

RATIONALE: Cryptogenic strokes, those of unknown cause, have been estimated as high as 30% to 40% of strokes. Inflammation has been suggested as a critical etiologic factor. However, there is lack of experimental evidence. OBJECTIVE: In this study, we investigated inflammation-associated stroke using a mouse model that developed spontaneous stroke because of myeloid deficiency of TGF-ß (transforming growth factor-ß) signaling. METHODS AND RESULTS: We report that mice with deletion of Tgfbr2 in myeloid cells (Tgfbr2Myeko) developed cerebrovascular inflammation in the absence of significant pathology in other tissues, culminating in stroke and severe neurological deficits with 100% penetrance. The stroke phenotype can be transferred to syngeneic wild-type mice via Tgfbr2Myeko bone marrow transplant and can be rescued in Tgfbr2Myeko mice with wild-type bone marrow. The underlying mechanisms involved an increased type 1 inflammation and cerebral endotheliopathy, characterized by elevated NF-κB (nuclear factor-κB) activation and TNF (tumor necrosis factor) production by myeloid cells. A high-fat diet accelerated stroke incidence. Anti-TNF treatment, as well as metformin and methotrexate, which are associated with decreased stroke risk in population studies, delayed stroke occurrence. CONCLUSIONS: Our studies show that TGF-ß signaling in myeloid cells is required for maintenance of vascular health and provide insight into inflammation-mediated cerebrovascular disease and stroke.

Differences in cerebral and hepatic oxygenation in response to intradialytic blood transfusion in patients undergoing hemodialysis.

Hemodialysis (HD) patients frequently experience severe anemia, requiring intradialytic blood transfusion. Severe anemia leads to deterioration of systemic tissue oxygenation. However, few reports have examined the effect of intradialytic blood transfusion on tissue oxygenation changes. This study aimed to (i) monitor the differences in tissue oxygenation in the brain and liver during intradialytic blood transfusion, and (ii) elucidate the clinical factors affecting cerebral and hepatic oxygenation. Thirty-eight HD patients with severe anemia requiring intradialytic blood transfusion were included (27 men, 11 women; mean age, 70.2 ± 1.6 years). Cerebral and hepatic regional oxygen saturation (rSO2) values were monitored using near-infrared spectroscopy (INVOS 5100c oxygen saturation monitor). Cerebral and hepatic rSO2 were significantly higher after than before blood transfusion (p < 0.001, both). Furthermore, hepatic rSO2 was significantly higher than cerebral rSO2 after transfusion (p = 0.004). In multivariable linear regression analysis, cerebral rSO2 changes were independently associated with the natural logarithm of hemoglobin (Hb) ratio (Hb after/before transfusion) (standardized coefficient: 0.367, p = 0.023), whereas hepatic rSO2 changes were independently associated with the natural logarithm of [Hb ratio/colloid osmotic pressure ratio (colloid osmotic pressure after/before transfusion)] (standardized coefficient: 0.378, p = 0.019). In conclusion, throughout intradialytic blood transfusion, brain and liver tissue oxygenation improved. Hepatic rSO2 was significantly higher than cerebral rSO2 at the end of HD. Furthermore, cerebral oxygenation changes were associated with only transfusion-induced Hb increase, whereas hepatic oxygenation changes were associated with both transfusion-induced Hb increase (positive changes) and ultrafiltration-induced colloid osmotic pressure increase (negative changes).

Performance of the DOSIRIS™ eye lens dosimeter.

Monitoring and protecting of occupational eye doses in interventional radiology (IR) are very important matters. DOSIRIS™ is the useful solution to estimate the 3 mm dose-equivalent (Hp(3)), and it can be worn behind lead glasses. And DOSIRIS™, adjustable according to 3 axes, it is ideally placed as close to the eye and in contact with the skin. So, DOSIRIS™ will be suitable eye lens dosimeter. However, the fundamental characteristics of the DOSIRIS™ in the diagnostic x-ray energy domain (including that of IR x-ray systems) remain unclear. Here, we evaluated the performance of the dosimeter in that energy range. As a result, the DOSIRIS™ has good fundamental characteristics (batch uniformity, dose linearity, energy dependence, and angular dependence) in the diagnostic x-ray energy domain. We conclude that the DOSIRIS™ has satisfactory basic performance for occupational eye dosimetry in diagnostic x-ray energy settings (including IR x-ray systems).

An ascovirus isolated from Spodoptera litura (Noctuidae: Lepidoptera) transmitted by the generalist endoparasitoid Meteorus pulchricornis (Braconidae: Hymenoptera).

The family Ascoviridae is a recently described virus family whose members are transmitted by parasitoids and cause chronic and lethal infections in lepidopteran insects. Little is known about the biology and ecology of ascoviruses, and few isolates have been found outside the United States. We report here the isolation of a new ascovirus variant from Spodoptera litura in Japan. Full genome sequence and phylogenetic analyses showed that this virus was closely related to variants in Heliothis virescens ascovirus-3a, and it was named HvAV-3j. HvAV-3j has a DNA genome of 191 718 bp, with 189 putative ORFs and a GC content of 45.6 %, and is highly similar to HvAV-3h, which was isolated in China. In a field survey, the endoparasitoid Meteorus pulchricornis caused a high percentage of parasitization in populations of S. litura larvae, and under laboratory conditions M. pulchricornis was able to transmit HvAV-3j from infected to uninfected larvae by oviposition. Meteorus pulchricornis is thus likely to be a major vector for HvAV-3j transmission in Japan. This species is recognized here for the first time as a vector of ascoviruses that parasitizes a range of host species that extends across families.

Differences in tissue oxygenation and changes in total hemoglobin signal strength in the brain, liver, and lower-limb muscle during hemodialysis.

Near-infrared spectroscopy has been used to measure regional saturation of oxygen (rSO2) based on the total hemoglobin (t-Hb) signal strength. To date, few studies have investigated the changes of systemic oxygenation and t-Hb signal strength during hemodialysis (HD). This study aimed to (1) monitor rSO2 and t-Hb signal strength in the brain, liver, and lower-limb muscle during HD and (2) clarify the differences in rSO2 and t-Hb signal strength in each compartment. Fifty-three patients receiving 4-h HD were included and divided into three groups according to the compartments in which tissue oxygenation was measured as follows: brain (n = 44), liver (n = 42), and lower-limb muscle (n = 40). The rSO2 and t-Hb signal strength was monitored using an INVOS 5100c (Covidien Japan, Tokyo, Japan). The rSO2 levels were significantly lower in the brain than in the liver from HD initiation to the end (HD initiation: rSO2 in the brain and liver, 46.5 ± 1.3 and 52.4 ± 1.7%, respectively, p = 0.031). Furthermore, compared to the t-Hb signal strength ratio [value at t (min) during HD/initial value before HD] in the brain during HD, there were significant increases in the liver and lower-limb muscle, respectively. In conclusion, deterioration of cerebral oxygenation was remarkable compared to the hepatic oxygenation in HD patients. Our results, which revealed significant differences among the t-Hb signal strength ratios in the brain, liver, and lower-limb muscle during HD, might reflect the non-uniform body-fluid reduction within systemic tissues induced by ultrafiltration.

Correlations of Enzyme Levels at Birth in Stressed Neonates with Short-Term Outcomes.

INTRODUCTION: Multi-organ injury causes leakage of several intracellular enzymes into the circulation. We evaluated the correlation between the serum-leaked intracellular enzyme levels at the beginning of treatment and the outcome in perinatally stressed neonates. MATERIALS AND METHODS: We retrospectively studied neonates whose 1 minute Apgar score was < 7. We collected initial venous blood sample data, including aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) levels, and correlated these with patient short-term outcomes. RESULTS: Of 60 neonates, nine patients were treated with therapeutic hypothermia, and 32 needed mechanical ventilation. The therapeutic hypothermia group showed significantly larger base deficit, and higher lactate, AST, ALT, LDH, and CK (all p < 0.01). The duration of mechanical ventilation significantly correlated with AST, ALT, LDH, and CK levels (all p < 0.01). CONCLUSION: Initial enzyme levels are useful for predicting the duration of mechanical ventilation in stressed neonates.

Epithelial splicing regulatory proteins 1 (ESRP1) and 2 (ESRP2) suppress cancer cell motility via different mechanisms.

ESRP1 (epithelial splicing regulatory protein 1) and ESRP2 regulate alternative splicing events associated with epithelial phenotypes of cells, and both are down-regulated during the epithelial-mesenchymal transition. However, little is known about their expression and functions during carcinogenesis. In this study, we found that expression of both ESRP1 and ESRP2 is plastic: during oral squamous cell carcinogenesis, these proteins are up-regulated relative to their levels in normal epithelium but down-regulated in invasive fronts. Importantly, ESRP1 and ESRP2 are re-expressed in the lymph nodes, where carcinoma cells metastasize and colonize. In head and neck carcinoma cell lines, ESRP1 and ESRP2 suppress cancer cell motility through distinct mechanisms: knockdown of ESRP1 affects the dynamics of the actin cytoskeleton through induction of Rac1b, whereas knockdown of ESRP2 attenuates cell-cell adhesion through increased expression of epithelial-mesenchymal transition-associated transcription factors. Down-regulation of ESRP1 and ESRP2 is thus closely associated with a motile phenotype of cancer cells.

Lung functions of Japanese patients with chronic rhinosinusitis who underwent endoscopic sinus surgery.

BACKGROUND: Chronic rhinosinusitis (CRS), which is clinically classified into CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP), shows considerable geographic differences and heterogeneity. Eosinophilic (E) CRS with nasal polyps (ECRSwNP) has a higher degree of disease severity and higher frequency of comorbid asthma. Epidemiologic studies in different ethnic populations have improved understanding of the pathophysiology of the disease. Here we report the clinical characteristics of Japanese patients with medically refractory CRS undergoing endoscopic sinus surgery (ESS). METHODS: We recruited a total of 210 CRS patients and assessed them by nasal endoscopy, the Lund-Mackay score using computed tomography (CT), peripheral eosinophilia and smoking status. We also examined the comorbidity of asthma, effects of age and lung functions in the patients. RESULTS: In this study, 13% of CRSwNP patients and 20% of CRSwNP patients with peripheral blood eosinophilia exhibited obstructive lung dysfunction (FEV1/FVC <70%) despite the absence of an asthma diagnosis. Among elderly nonsmoker patients (≥ 60 years) who had never been diagnosed with asthma, 50% of CRSwNP patients with peripheral blood eosinophilia showed decreased FEV1/FVC <70%. CONCLUSIONS: Our findings suggest that asthma is under-diagnosed in CRS patients who undergo ESS, especially the elderly. Although the association between CRS and asthma has been recognized, increased attention to the comorbidity of obstructive airway diseases such as asthma is still needed for management of medically refractory CRS.

Constipation-associated factors in outpatients with schizophrenia: A multicenter questionnaire survey.

Constipation is a prevalent gastrointestinal disorder that affects people globally, decreasing their quality of life and life expectancy. Individuals with schizophrenia often suffer from constipation, which could be a result of the illness itself or the side effects of psychotropic medications. However, little research has been conducted on factors contributing to constipation in individuals with schizophrenia. To address this issue, we conducted a survey using self-administered questionnaires and medical records to identify factors associated with constipation in psychiatric outpatients. This study included 399 patients with schizophrenia, resulting in a high prevalence of constipation (43.4%). The analysis suggested that female gender, the doses of antiparkinsonian medications, and benzodiazepine sleeping pills may be associated with constipation.

Relationship Between Insomnia and Continued Outpatient Treatment in Psychiatric Patients.

Purpose: Sleep plays an essential role in maintaining both physical and mental well-being. Many patients in psychiatric outpatient settings complain of insomnia. However, the causal relationship between insomnia and depressive symptoms in all mental illnesses remains unclear. Moreover, research on insomnia and the continuation of outpatient treatment is lacking. We hypothesize a high correlation between depression and insomnia among patients with diverse mental illnesses. Additionally, we posit that insomnia significantly influences the continuity of outpatient visits. To this end, we evaluated insomnia and depression symptoms in psychiatric patients both at their initial visit and one year later. We also examined factors related to insomnia at the outset and factors associated with the ongoing utilization of outpatient treatment. Patients and Methods: The participants of the study consisted of patients who made their first visit to the outpatient department of psychiatry and neurology at Showa University East Hospital between June 1, 2021, and March 31, 2023, and who continued attending the outpatient clinic for one year. Clinical characteristics were assessed using the Self-rating Depression Scale (SDS) and the Athens Insomnia Scale (AIS). Results: The study's findings were collected from a cohort of 1106 patients and revealed that more than 70% experienced insomnia at the time of their initial visit. In total 137 patients continued to receive outpatient treatment for one year, and their AIS scores improved from 9 points to 5 points. A multivariate analysis revealed that the SDS items of depressed mood and insomnia were confounding factors influencing AIS improvement. Conclusion: Given that 70% of patients complained of insomnia at the time of their first visit and that sleep improved in many of the 12.4% of patients who continued to receive outpatient treatment for at least one year, the results suggest that sleep status is an important determinant of whether a patient continues to attend outpatient clinics.

Alteration of cancer stem cell-like phenotype by histone deacetylase inhibitors in squamous cell carcinoma of the head and neck.

Recent progression in the understanding of stem cell biology has greatly facilitated the identification and characterization of cancer stem cells (CSCs). Moreover, evidence has accumulated indicating that conventional cancer treatments are potentially ineffective against CSCs. Histone deacetylase inhibitors (HDACi) have multiple biologic effects consequent to alterations in the patterns of acetylation of histones and are a promising new group of anticancer agents. In this study, we investigated the effects of two HDACi, suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA), on two CD44+ cancer stem-like cell lines from squamous cell carcinoma of the head and neck (SCCHN) cultured in serum-free medium containing epidermal growth factor and basic fibroblast growth factor. Histone deacetylase inhibitors inhibited the growth of SCCHN cell lines in a dose-dependent manner as measured by MTS assays. Moreover, HDACi induced cell cycle arrest and apoptosis in these SCCHN cell lines. Interestingly, the expression of cancer stem cell markers, CD44 and ABCG2, on SCCHN cell lines was decreased by HDACi treatment. In addition, HDACi decreased mRNA expression levels of stemness-related genes and suppressed the epithelial-mesencymal transition phenotype of CSCs. As expected, the combination of HDACi and chemotherapeutic agents, including cisplatin and docetaxel, had a synergistic effect on SCCHN cell lines. Taken together, our data indicate that HDACi not only inhibit the growth of SCCHN cell lines by inducing apoptosis and cell cycle arrest, but also alter the cancer stem cell phenotype in SCCHN, raising the possibility that HDACi may have therapeutic potential for cancer stem cells of SCCHN.