The development of early human lymphatic vessels as characterized by lymphatic endothelial markers.

Lymphatic vessel development studies in mice and zebrafish models have demonstrated that lymphatic endothelial cells (LECs) predominantly differentiate from venous endothelial cells via the expression of the transcription factor Prox1. However, LECs can also be generated from undifferentiated mesoderm, suggesting potential diversity in their precursor cell origins depending on the organ or anatomical location. Despite these advances, recapitulating human lymphatic malformations in animal models has been difficult, and considering lymphatic vasculature function varies widely between species, analysis of development directly in humans is needed. Here, we examined early lymphatic development in humans by analyzing the histology of 31 embryos and three 9-week-old fetuses. We found that human embryonic cardinal veins, which converged to form initial lymph sacs, produce Prox1-expressing LECs. Furthermore, we describe the lymphatic vessel development in various organs and observe organ-specific differences. These characterizations of the early development of human lymphatic vessels should help to better understand the evolution and phylogenetic relationships of lymphatic systems, and their roles in human disease.

Assessment for Carotid Atherosclerotic Plaque Using Vessel Wall Magnetic Resonance Imaging: A Multireader ROC Study to Determine Optimal Sequence for Detecting Vessel Wall Calcification.

INTRODUCTION: We aimed to compare conventional vessel wall MR imaging techniques and quantitative susceptibility mapping (QSM) to determine the optimal sequence for detecting carotid artery calcification. METHODS: Twenty-two patients who underwent carotid vessel wall MR imaging and neck CT were enrolled. Four slices of 6-mm sections from the bilateral internal carotid bifurcation were subdivided into 4 segments according to clock position (0-3, 3-6, 6-9, and 9-12) and assessed for calcification. Two blinded radiologists independently reviewed a total of 704 segments and scored the likelihood of calcification using a 5-point scale on spin-echo imaging, FLASH, and QSM. The observer performance for detecting calcification was evaluated by a multireader, multiple-case receiver operating characteristic study. Weighted κ statistics were calculated to assess interobserver agreement. RESULTS: QSM had a mean area under the receiver operating characteristic curve of 0.85, which was significantly higher than that of any other sequence (p < 0.01) and showed substantial interreader agreement (κ = 0.68). A segment with a score of 3-5 was defined as positive, and a segment with a score of 1-2 was defined as negative; the sensitivity and specificity of QSM were 0.75 and 0.87, respectively. CONCLUSION: QSM was the most reliable MR sequence for the detection of plaque calcification.

Oscillating Gradient Diffusion-Weighted MRI for Risk Stratification of Uterine Endometrial Cancer.

BACKGROUND: Oscillating gradient diffusion-weighted imaging (DWI) enables elucidation of microstructural characteristics in cancers; however, there are limited data to evaluate its utility in patients with endometrial cancer. PURPOSE: To investigate the utility of oscillating gradient DWI for risk stratification in patients with uterine endometrial cancer compared with conventional pulsed gradient DWI. STUDY TYPE: Retrospective. SUBJECTS: Sixty-three women (mean age: 58 [range: 32-85] years) with endometrial cancer. FIELD STRENGTH/SEQUENCE: 3 T MRI including DWI using oscillating gradient spin-echo (OGSE) and pulsed gradient spin-echo (PGSE) research sequences. ASSESSMENT: Mean value of the apparent diffusion coefficient (ADC) values for OGSE (ADCOGSE ) and PGSE (ADCPGSE ) as well as the ADC ratio (ADCOGSE /ADCPGSE ) within endometrial cancer were measured using regions of interest. Prognostic factors (histological grade, deep myometrial invasion, lymphovascular invasion, International Federation of Gynecology and Obstetrics [FIGO] stage, and prognostic risk classification) were tabulated. STATISTICAL TESTS: Interobserver agreement was analyzed by calculating the intraclass correlation coefficient. The associations of ADCOGSE , ADCPGSE , and ADCOGSE /ADCPGSE with prognostic factors were examined using the Kendall rank correlation coefficient, Mann-Whitney U test, and receiver operating characteristic (ROC) curve. A P value of <0.05 was statistically significant. RESULTS: Compared with ADCOGSE and ADCPGSE , ADCOGSE /ADCPGSE was significantly and strongly correlated with histological grade (observer 1, τ = 0.563; observer 2, τ = 0.456), FIGO stage (observer 1, τ = 0.354; observer 2, τ = 0.324), and prognostic risk classification (observer 1, τ = 0.456; observer 2, τ = 0.385). The area under the ROC curves of ADCOGSE /ADCPGSE for histological grade (observer 1, 0.92, 95% confidence intervals [CIs]: 0.83-0.98; observer 2, 0.84, 95% CI: 0.73-0.92) and prognostic risk (observer 1, 0.80, 95% CI: 0.68-0.89; observer 2, 0.76, 95% CI: 0.63-0.86) were significantly higher than that of ADCOGSE and ADCPGSE . DATA CONCLUSION: The ADC ratio obtained via oscillating gradient and pulsed gradient DWIs might be useful imaging biomarkers for risk stratification in patients with endometrial cancer. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Impact of fat on the apparent T1 value of the liver: assessment by water-only derived T1 mapping.

OBJECTIVES: To determine the impact of fat on the apparent T1 value of the liver using water-only derived T1 mapping. METHODS: 3-T MRI included 2D Look-Locker T1 mapping and proton density fat fraction (PDFF) mapping. T1 values of the liver were compared among T1 maps obtained by in-phase (IP), opposed-phase (OP), and Dixon water sequences using paired t-test. The correlation between T1 values of the liver on each T1 map and PDFF was assessed using Spearman correlation coefficient. The absolute differences between T1 value of the liver on Dixon water images and that on IP or OP images were also correlated with PDFF. RESULTS: One hundred sixty-two patients (median age, 70 [range, 24-91] years, 90 men) were retrospectively evaluated. The T1 values of the liver on each T1 map were significantly different (p < 0.001). The T1 value of the liver on IP images was significantly negatively correlated with PDFF (r = - 0.438), while the T1 value of the liver on OP images was slightly positively correlated with PDFF (r = 0.164). The T1 value of the liver on Dixon water images was slightly negatively correlated with PDFF (r = - 0.171). The absolute differences between T1 value of the liver on Dixon water images and that on IP or OP images were significantly correlated with PDFF (r = 0.606, 0.722; p < 0.001). CONCLUSION: Fat correction for the apparent T1 value by water-only derived T1 maps will be helpful for accurately evaluating the T1 value of the liver. CLINICAL RELEVANCE STATEMENT: Fat-corrected T1 mapping of the liver with the water component only obtained from the 2D Dixon Look-Locker sequence could be useful for accurately evaluating the T1 value of the liver without the impact of fat in daily clinical practice. KEY POINTS: • The T1 values of the liver on the conventional T1 maps are significantly affected by the presence of fat. • The apparent T1 value of the liver on water-only derived T1 maps would be slightly impacted by the presence of fat. • Fat correction for the apparent T1 values is necessary for the accurate assessment of the T1 values of the liver.

Psychological characteristics of Japanese patients and their family members receiving genetic counseling: A single-institute exploratory study.

In Japan, clinical genetic services became available in the 1970s, and genomic medicine, including genetic counseling (GC), developed rapidly. However, research on the outcomes of GC in Japan is limited. Japan has a unique cultural context, and appropriate GC methods have not yet been optimized for this population. The current study aimed to evaluate the psychological status of Japanese patients and their companions undergoing GC and the outcomes of GC. We used the Quality of Care Through the Patients' Eyes-gene cancer (QUOTE-geneCA ), the Genetic Counseling Outcome Scale-24 (GCOS-24), and the State-Trait Anxiety Inventory (STAI) to evaluate patients and their companions' needs and preferences regarding GC, empowerment, and anxiety, respectively. We evaluated stress status during GC by measuring saliva cortisol levels. QUOTE-geneCA results for patients (n = 69) and a group of patients and their companions (n = 96) revealed that participants felt that it was important that skilled medical staff explained medical information and provided advice in an easily understandable manner. Japanese patients and their companions regarded the procedural aspects of counseling as most important and their autonomy in decision-making as less important. GCOS-24 results revealed a significant increase in empowerment scores in 38 patients (by 9.63 points) from pre- to post-GC (p < 0.001; Cohen's d = 0.79). STAI results revealed a significant decrease in state anxiety for patients (6.11 points; p < 0.001; Cohen's d = 0.66). Cortisol levels in patients significantly decreased after GC (p = 0.001). The improvement of empowerment scores from pre- to post-GC among patients and their companions were significantly negatively correlated with pre-GC empowerment scores (p < 0.001), trait anxiety scores (p = 0.001), and the number of people living together (p = 0.011). The change of cortisol levels during GC in patients and their companions was significantly positively correlated with trait anxiety score (p = 0.027). This study suggested that these characteristics of Japanese patients and their companions may predict GC outcomes.

Effect of an Internet-Delivered Cognitive Behavioral Therapy-Based Sleep Improvement App for Shift Workers at High Risk of Sleep Disorder: Single-Arm, Nonrandomized Trial.

BACKGROUND: Shift workers are at high risk of developing sleep disorders such as shift worker sleep disorder or chronic insomnia. Cognitive behavioral therapy (CBT) is the first-line treatment for insomnia, and emerging evidence shows that internet-based CBT is highly effective with additional features such as continuous tracking and personalization. However, there are limited studies on internet-based CBT for shift workers with sleep disorders. OBJECTIVE: This study aimed to evaluate the impact of a 4-week, physician-assisted, internet-delivered CBT program incorporating machine learning-based well-being prediction on the sleep duration of shift workers at high risk of sleep disorders. We evaluated these outcomes using an internet-delivered CBT app and fitness trackers in the intensive care unit. METHODS: A convenience sample of 61 shift workers (mean age 32.9, SD 8.3 years) from the intensive care unit or emergency department participated in the study. Eligible participants were on a 3-shift schedule and had a Pittsburgh Sleep Quality Index score ≥5. The study comprised a 1-week baseline period, followed by a 4-week intervention period. Before the study, the participants completed questionnaires regarding the subjective evaluation of sleep, burnout syndrome, and mental health. Participants were asked to wear a commercial fitness tracker to track their daily activities, heart rate, and sleep for 5 weeks. The internet-delivered CBT program included well-being prediction, activity and sleep chart, and sleep advice. A job-based multitask and multilabel convolutional neural network-based model was used for well-being prediction. Participant-specific sleep advice was provided by sleep physicians based on daily surveys and fitness tracker data. The primary end point of this study was sleep duration. For continuous measurements (sleep duration, steps, etc), the mean baseline and week-4 intervention data were compared. The 2-tailed paired t test or Wilcoxon signed rank test was performed depending on the distribution of the data. RESULTS: In the fourth week of intervention, the mean daily sleep duration for 7 days (6.06, SD 1.30 hours) showed a statistically significant increase compared with the baseline (5.54, SD 1.36 hours; P=.02). Subjective sleep quality, as measured by the Pittsburgh Sleep Quality Index, also showed statistically significant improvement from baseline (9.10) to after the intervention (7.84; P=.001). However, no significant improvement was found in the subjective well-being scores (all P>.05). Feature importance analysis for all 45 variables in the prediction model showed that sleep duration had the highest importance. CONCLUSIONS: The physician-assisted internet-delivered CBT program targeting shift workers with a high risk of sleep disorders showed a statistically significant increase in sleep duration as measured by wearable sensors along with subjective sleep quality. This study shows that sleep improvement programs using an app and wearable sensors are feasible and may play an important role in preventing shift work-related sleep disorders. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/24799.

Evaluation of diffusion-weighted magnetic resonance imaging of the rectal cancers: comparison between modified reduced field-of-view single-shot echo-planar imaging with tilted two-dimensional radiofrequency excitation pulses and conventional full field-of-view readout-segmented echo-planar imaging.

PURPOSE: To evaluate the image quality qualitatively and quantitatively, as well as apparent diffusion coefficient (ADC) values of modified reduced field-of-view diffusion-weighted magnetic resonance imaging (MRI) using spatially tailored two-dimensional radiofrequency pulses with tilted excitation plane (tilted r-DWI) based on single-shot echo planar imaging (SS-EPI) compared with full-size field-of-view DWI (f-DWI) using readout segmented (RS)-EPI in patients with rectal cancer. MATERIALS AND METHODS: Twenty-two patients who underwent an MRI for further evaluation of rectal cancer were included in this retrospective study. All MR images were analyzed to compare image quality, lesion conspicuity, and artifacts between f-DWI with RS-EPI and tilted r-DWI with SS-EPI. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and ADC values were also compared. The Wilcoxon signed-rank test or paired t test was performed to compare the qualitative and quantitative assessments. RESULTS: All image quality scores, except aliasing artifacts, were significantly higher (p < 0.01 for all) in tilted r-DWI than f-DWI with RS-EPI. CNR in tilted r-DWI was significantly higher than in f-DWI with RS-EPI (p < 0.01), while SNR was not significantly different. Regarding the ADC values, no significant difference was observed between tilted r-DWI and f-DWI with RS-EPI (p = 0.27). CONCLUSION: Tilted r-DWI provides a better image quality with fewer artifacts and higher rectal lesion conspicuity than f-DWI with RS-EPI, indicating the feasibility of this MR sequence in evaluating rectal cancer in clinical practice.

Pancreatic hamartoma: detection of harbouring NAB2::STAT6 fusion gene.

Hamartomas in the pancreas are rare and are often histologically and morphologically similar to solitary fibrous tumours (SFTs). We examined the differences between hamartomas and SFTs at the molecular level. METHODS AND RESULTS: Thirteen patients histopathologically diagnosed with pancreatic hamartoma were included in the study. We also performed STAT6 immunohistochemistry (IHC), which is used in the diagnosis of SFT. Furthermore, for the three cases in which RNA was extracted, reverse transcription polymerase chain reaction to search for NAB2::STAT6 fusions was used. Macroscopically, 13 patients had well-demarcated tumour lesions. Histologically, no islets of Langerhans were observed in the lesions, acinar tissue and ducts were unevenly distributed and elastic fibres were not observed around the ducts by Elastica van Gieson staining. One case contained a lipomatous hamartoma composed mainly of adipose tissue. Seven of the 13 cases demonstrated expression of STAT6 in the nuclei of intervening spindle cells. NAB2::STAT6 fusions were observed in two of the three cases in which RNA was extracted. These two cases also demonstrated STAT6 expression in spindle cells using STAT6 IHC. In one case of lipomatous hamartoma, we did not confirm NAB2::STAT6 fusion or STAT6 expression in STAT6 IHC. CONCLUSION: Of the 13 patients histopathologically diagnosed with hamartoma, two demonstrated NAB2::STAT6 fusions, suggesting the existence of pancreatic hamartomas with molecular-level components identical to those of SFT.

Preiser disease in a child before complete ossification of the scaphoid: a case report.

BACKGROUND: The pathology of Preiser disease remains controversial, and treatment for Preiser disease has not yet been standardised. Preiser disease itself is rare, and although it can be found in children, its presentation is even rarer; therefore, the treatment of paediatric patients with Preiser disease is more unclear than adult cases. CASE PRESENTATION: A 10-year-old boy who complained of left wrist pain was diagnosed with Preiser disease from osteosclerosis and segmentation on plain radiography and computed tomography, and low signal intensity on both T1- and T2-weighted images on magnetic resonance imaging. Because the patient was a child whose scaphoid was immature and pre-ossified, we chose a conservative immobilisation treatment with a thumb spica cast followed by an orthosis. After 3 months of immobilisation, the distal pole of the scaphoid showed remodelling. One year after the initial visit, plain radiography showed remodelling of the whole scaphoid, although magnetic resonance T1-weighted image showed that the recovery of intensity change was only observed in the distal pole. Two years after the initial visit, both plain radiography and magnetic resonance imaging showed a normal appearance and 5 years after the initial visit; the scaphoid bone showed normal development. CONCLUSIONS: This is the first case report of Preiser disease before complete ossification of the scaphoid; therefore, we cannot say anything definitive about the treatment strategy. However, our experience suggests that conservative treatment may provide a cure for Preiser disease in children with immature ossification of the scaphoid without carpal collapse.

Relationship between Neurological Deterioration and Blood Pressure/Heart Rate Variability in Patients with Acute Cerebral Infarction.

OBJECTIVES: Neurological deterioration (ND) during hospitalization is an independent predictor of poor prognosis after stroke. Risk factors affecting early ND within 48 h post stroke have been intensively investigated, while few data are available on those for late ND after transfer to a wheelchair. Therefore, it was investigated whether hemodynamic factors may affect the late ND during hospitalization. MATERIALS AND METHODS: A retrospective study was conducted on 135 patients with atherothrombotic or cardiogenic cerebral infarction who were admitted to our hospital between April 1st, 2014 and July 31st, 2017. During hospitalization, average, maximum, and minimum values were determined for systolic blood pressure (sBP), diastolic BP (dBP), and heart rate (HR), respectively.135 patients were classified into two groups; ND (+) group, in which modified Barthel index score at the time of transfer to a wheelchair showed five points or more decrease between wheelchair transfer and discharge, and ND (-) group, which did not. Vital indices were compared between the two groups and subjected to ROC-curve analysis. RESULTS: The ND (+) group included 32 patients, and the ND (-) 103. Significant differences were found between the groups in four items; sBPmin (p = 0.029), dBPmin (p = 0.019), HRave (p = 0.028), and HRmax (p < 0.01). The ND (+) group showed lower sBPmin and dBPmin, and higher HRave and HRmax than the ND (-) group. CONCLUSIONS: Late ND after transfer to a wheelchair is related to the vital indices during hospitalization and should be cautiously managed to prevent late ND.

Oncocytic intraductal carcinoma of salivary glands: a distinct variant with TRIM33-RET fusions and BRAF V600E mutations.

AIMS: Salivary gland intraductal carcinoma (IDC) is a complex ductal neoplasm surrounded by a layer of myoepithelial cells. Recent insights have shown that there are three different types: intercalated duct-like, with frequent NCOA4-RET fusions; apocrine, with salivary duct carcinoma-like mutations; and mixed intercalated duct-like/apocrine, with RET fusions, including TRIM27-RET. In addition, an oncocytic IDC has been described, but it remains unclear whether it represents a fourth variant or simply oncocytic metaplasia of another IDC type. Our aim was to more completely characterize oncocytic IDC. METHODS AND RESULTS: Six IDCs with oncocytic changes were retrieved from the authors' archives, from three men and three women ranging in age from 45 to 75 years (mean, 63 years). Five arose in the parotid gland, with one in an accessory parotid gland. Four patients with follow-up were free of disease after 1-23 months. Several immunostains (S100, mammaglobin, androgen receptor, and p63/p40) and molecular tools (RNA sequencing, RET fluorescence in-situ hybridisation, BRAF V600E VE1 immunohistochemistry, and Sanger sequencing) were applied. Histologically, the tumours were variably cystic with solid intracystic nodules often difficult to recognise as intraductal. In all, tumour ducts were positive for S100 and mammaglobin, negative for androgen receptor, and completely surrounded by myoepithelial cells positive for p63/p40. Molecular analysis revealed TRIM33-RET in two of six cases, NCOA4-RET in one of six cases, and BRAF V600E in two of six cases. One case had no identifiable alterations. CONCLUSIONS: Oncocytic IDC shares similarities with intercalated duct-like IDC. Although additional verification is needed, the oncocytic variant appears to be sufficiently unique to be now regarded as the fourth distinct subtype of IDC. Because of its indolent nature, oncocytic IDC should be distinguished from histological mimics.

Reduced Field-of-View Diffusion-Weighted Magnetic Resonance Imaging of the Pancreas With Tilted Excitation Plane: A Preliminary Study.

BACKGROUND: Reduced field-of-view diffusion-weighted imaging (rDWI) with tilted two-dimensional radiofrequency (RF) excitation planes has not yet been applied to the imaging of the pancreas although the utility of this technique which allows the acquisition of high-quality images without aliasing artifacts in the phase-encoding direction has been evaluated for brain and spinal cord imaging. PURPOSE: To evaluate the visual image quality of the pancreas by tilting the excitation plane (tilted rDWI) in comparison to conventional DWI (cDWI) and rDWI without using the tilted excitation plane. STUDY TYPE: Retrospective. POPULATION: Thirty-two patients evaluated for suspected pancreatobiliary diseases. FIELD STRENGTH/SEQUENCE: Echo-planar imaging DWI (cDWI, rDWI, and tilted rDWI) acquired at 3 T. ASSESSMENT: Images from each DWI sequence were analyzed by five radiologists to compare image quality (conspicuity of pancreatic edges, interslice signal homogeneity, overall image quality, and conspicuity of focal pancreatic lesions) and artifacts (presence of blurring or ghosting artifacts, susceptibility artifacts, and aliasing artifact). STATISTICAL TESTS: Shapiro-Wilk test was performed to assess whether data were normally distributed. Friedman test followed by Bonferroni-adjusted Wilcoxon signed-rank test for post hoc analysis was performed to compare image quality and artifact scores. RESULTS: The mean scores for conspicuity of pancreatic edges (3.36 vs. 2.37), interslice signal homogeneity (3.14 vs. 2.81), presence of ghosting artifacts (3.32 vs. 2.66), susceptibility artifacts (3.06 vs. 2.30), and aliasing artifacts (3.90 vs. 2.34), and overall image quality (3.49 vs. 2.36) were significantly higher in the tilted rDWI than in the rDWI (P < 0.017 for all parameters). The conspicuity score for focal pancreatic lesions tended to be higher in tilted rDWI than in rDWI (2.44 vs. 2.00, P = 0.07). DATA CONCLUSION: Tilted rDWI had better image quality and reduced artifacts relative to cDWI and rDWI techniques in the pancreas. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Impact of Helicopter Transport on Reperfusion Times and Long-Term Outcomes in Acute Myocardial Infarction Patients in Rural Areas: A Report From the Mie Acute Coronary Syndrome Registry.

OBJECTIVE: Helicopter emergency medical services (HEMS) are effective for time-sensitive conditions, such as stroke and trauma. However, prognostic data on helicopter transport for acute myocardial infarction (AMI) patients are insufficient. METHODS: We registered 2,681 AMI patients in the Mie Acute Coronary Syndrome Registry and enrolled 163 patients from rural areas to HEMS base hospitals with HEMS or ground emergency medical services (GEMS). They were categorized into 4 groups according to the transportation method for interhospital transfer (direct HEMS: n = 52, direct GEMS: n = 54, interhospital HEMS: n = 32, and interhospital GEMS: n = 25). The primary end point was the emergency medical services (EMS) call-to-balloon time. The secondary end point was 2-year major adverse cardiac and cerebrovascular events. RESULTS: The direct HEMS group was younger than the direct GEMS group (P = .029). The EMS call-to-balloon time was shorter in the direct HEMS and interhospital HEMS groups than in each GEMS group (P = .015 and P = .046). The incidence of 2-year major adverse cardiac and cerebrovascular events tended to be lower in both HEMS groups than in each GEMS group. CONCLUSION: Direct HEMS for AMI in rural areas shortens the time from the EMS call to reperfusion when the transport distance is expected to exceed 30 km, which may result in a better patient prognosis. In addition, prehospital diagnostic modalities, such as 12-lead electrocardiography and echocardiography, may shorten the duration from the EMS call to reperfusion.

The Evaluation of Helicopter Emergency Medical Services With a Physician for Acute Myocardial Infarction in Japan: A Registry-Based Study of Prognosis and Time Reduction.

OBJECTIVE: The aim of this study was to compare the prognosis and time reduction between helicopter emergency medical services (HEMS) with a physician and ground emergency medical services (GEMS) in acute myocardial infarction (AMI) cases. METHODS: This is a registry-based study of the Japan Helicopter Emergency Medical Service Registry from April 1, 2015, to March 31, 2018. RESULTS: A total of 605 cases of AMI were registered in the HEMS group and 794 cases in the GEMS group. In the cases of non-cardiopulmonary arrest (CPA), the prognosis between HEMS and GEMS did not differ significantly. Regarding the road distance, for ranges of 20 to 40 km and > 40 km, the times from the call to the angiography room were significantly shorter with HEMS than GEMS (median 91 vs. 97 minutes, P = .036 and 101 vs. 132 minutes, P = .002, respectively). In cases of CPA, HEMS had a higher rate of return of spontaneous circulation than GEMS (55.3% vs. 36.8%, P = .038), but HEMS had a lower prognosis than GEMS (22.9% vs. 38.9%, P = .036). CONCLUSION: The present study suggested that HEMS had an advantage in reducing the time to angiography in AMI cases of non-CPA. In cases of CPA, HEMS increased the return of spontaneous circulation without improving the prognosis.

SOX11-induced decrease in vimentin and an increase in prostate cancer cell migration attributed to cofilin activity.

SOX11 is a transcription factor in the SOX family of genes that regulate multiple cellular events by influencing the expression of key genes in developmental, physiological, and tumorigenic cells. To elucidate the role of SOX11 in prostate cancer cells, PC-3 prostate cancer cells were cloned (S6 and S9 cells) to highly express SOX11. We demonstrated that both S6 and S9 lose vimentin expression, acquiring epithelial marker proteins, which indicates the Epithelial state phenotype. S6 and S9 cells have cancer-promoting characteristics that include higher migratory properties compared with control cells. The mechanisms that are responsible for the enhanced migration are cofilin activity and keratin 18 expression. TCGA (The Cancer Genome Atlas) dataset analysis revealed that metastatic prostate cancer tumors tend to have more SOX11 gene amplification compared with primary tumors. These results suggest the tumor promotive role and epithelial protein induction of SOX11 in prostate cancer cell.

Cancer-related gene mutations and intratumoral genetic heterogeneity in human epidermal growth factor receptor 2 heterogeneous gastric cancer.

Human epidermal growth factor receptor 2 (HER2) protein overexpression is associated with HER2 gene amplification, a critical driver oncogenetic change in gastric cancer. HER2 heterogeneity in advanced gastric cancer is associated with a poor prognosis and affects the clinical efficacy of trastuzumab. However, the mechanisms of HER2 heterogeneity are not fully understood. Here, we examined whether HER2 heterogeneous gastric cancer exhibited intratumoral genetic heterogeneity in other cancer-related genes. Two cases of advanced gastric cancer with HER2 heterogeneity were selected, and samples of HER2-positive and HER2-negative areas in each case were analyzed using a cancer-associated multiple gene panel. In both cases, TP53 mutations were observed in both HER2-positive and HER2-negative areas, whereas many of the potential driver and passenger mutations differed between HER2-positive and HER2-negative areas. Overall, our findings demonstrated that HER2 heterogeneous gastric cancer exhibited intratumoral genetic heterogeneity in other cancer-related genes and that the molecular mechanisms could differ between HER2-positive and -negative areas.

Invasive Salmonella Enteritidis infection complicated by bacterial meningitis and vertebral osteomyelitis shortly after influenza A infection in an immunocompetent young adult.

Non-typhoidal Salmonella usually manifests as a self-limited acute gastroenteritis but may also cause severe invasive infections almost exclusively among children or immunosuppressed patients. A previously healthy 22-year-old man developed high fever with coma, multiple organ failure and shock. He had visited another hospital complaining of fever 2 days previously and was diagnosed with a common cold. No obvious site of infection was identified by radiology and a rapid test for influenza A virus was positive, indicating possible influenza-associated encephalopathy. However, blood as well as CSF culture yielded Salmonella enterica serotype Enteritidis. Therefore, the patient was considered to be suffering from bacterial meningitis with septic shock concomitant with influenza infection. Antiviral drugs and therapy for septic shock were initiated. He stabilized relatively quickly and his mental status dramatically improved. The patient denied preceding gastrointestinal symptoms, but mentioned that he received positive fecal Salmonella species culture results without medical intervention about 3 months previously. His laboratory values showed marked improvement but his elevated inflammatory markers and fever were sustained. On the 17th day of hospitalization, he complained of back pain and MRI showed lumbar vertebral osteomyelitis. This case indicates that (i) invasive Salmonella infection can be developed even in previously healthy adults; (ii) chronic carriage of Salmonella is a predisposing factor to development of invasive infections, and influenza infection may contribute to such "breakthrough infections"; (iii) attention to manifestation of metastatic extra-intestinal foci even after resolution of sepsis is necessary.

Acquired factor XIII deficiency in two patients with bleeding events during veno-venous extracorporeal membrane oxygenation treatment.

We report two cases of acquired factor XIII deficiency with bleeding events during veno-venous extracorporeal membrane oxygenation (ECMO). Case 1: A 76-year-old man diagnosed with aspiration pneumonia after near-drowning was started on ECMO. Later, the patient presented with hemoptysis and anemia. Blood tests showed a decreased factor XIII activity of 29%. Although the patient recovered after receiving 1200 International Units of factor XIII concentrate, the patient had another episode of decreased factor XIII activity and bloody stool and was treated again with factor XIII concentrate. Case 2: A 48-year-old female diagnosed with pneumonia was started on ECMO. Soon after, she presented with hemoptysis and anemia. Blood tests showed a decreased factor XIII activity of 39%. The patient was treated with 720 IU of factor XIII concentrate with good recovery. Acquired factor XIII deficiency cannot be detected by routine coagulation tests, therefore it may be under-diagnosed in the ICU. Detection of acquired factor XIII deficiency is essential when treating a bleeding ECMO patient.

Social Network Analysis of Intensive Care Unit Health Care Professionals Measured by Wearable Sociometric Badges: Longitudinal Observational Study.

BACKGROUND: Use of wearable sensor technology for studying human teamwork behavior is expected to generate a better understanding of the interprofessional interactions between health care professionals. OBJECTIVE: We used wearable sociometric sensor badges to study how intensive care unit (ICU) health care professionals interact and are socially connected. METHODS: We studied the face-to-face interaction data of 76 healthcare professionals in the ICU at Mie University Hospital collected over 4 weeks via wearable sensors. RESULTS: We detail the spatiotemporal distributions of staff members' inter- and intraprofessional active face-to-face interactions, thereby generating a comprehensive visualization of who met whom, when, where, and for how long in the ICU. Social network analysis of these active interactions, concomitant with centrality measurements, revealed that nurses constitute the core members of the network, while doctors remain in the periphery. CONCLUSIONS: Our social network analysis using the comprehensive ICU interaction data obtained by wearable sensors has revealed the leading roles played by nurses within the professional communication network.

Outcomes of computer-assisted peri-acetabular osteotomy compared with conventional osteotomy in hip dysplasia.

AIM OF THE STUDY: To compare the outcomes after computer-assisted peri-acetabular osteotomy (PAO) and conventional PAO performed for hip dysplasia (DDH). METHODS: Ninety-one patients (98 hips) were enrolled in this study. In each case, DDH was treated with either conventional PAO, in which the angle and direction of the osteotomy was determined by intra-operative X-ray examination, or with computer-assisted PAO, which used the 3D navigation system. Forty hips underwent conventional PAO and 58 hips underwent computer-assisted PAO. RESULTS: Japanese Orthopaedic Association hip scores improved significantly from 70.0 points pre-operatively to 90.7 points post-operatively in patients with conventional PAO, and from 74.5 points pre-operatively to 94.2 points post-operatively in patients with computer-assisted PAO. In all patients with computer-assisted PAO, the post-operative AHI and VCA angle were within the radiographic target zone. Some patients with conventional PAO had post-operative AHI and VCA angle outside of the target zone. We performed total hip arthroplasty (THA) on five of the 98 PAO hips (5.1%) after an average follow-up period of 5.4 years. None of 58 hips (0%) with computer-assisted PAO was revised. DISCUSSION: Computer-assisted PAO enabled intra-operative confirmation of osteotomy sites, and the position of the osteotomized bone fragment could be confirmed in real time. Adequate anterior and lateral coverage of the femoral head in patients with computer-assisted PAO resulted in no need for early conversion to THA, in contrast to conventional PAO. CONCLUSION: Computer-assisted PAO not only improved accuracy and safety but also achieved sufficient anterior and lateral displacement to prevent the progression of DDH.