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.

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.

Differentiating primary central nervous system lymphoma from glioblastoma by time-dependent diffusion using oscillating gradient.

BACKGROUND: This study aimed to elucidate the impact of effective diffusion time setting on apparent diffusion coefficient (ADC)-based differentiation between primary central nervous system lymphomas (PCNSLs) and glioblastomas (GBMs) and to investigate the usage of time-dependent diffusion magnetic resonance imaging (MRI) parameters. METHODS: A retrospective study was conducted involving 21 patients with PCNSLs and 66 patients with GBMs using diffusion weighted imaging (DWI) sequences with oscillating gradient spin-echo (Δeff = 7.1 ms) and conventional pulsed gradient (Δeff = 44.5 ms). In addition to ADC maps at the two diffusion times (ADC7.1 ms and ADC44.5 ms), we generated maps of the ADC changes (cADC) and the relative ADC changes (rcADC) between the two diffusion times. Regions of interest were placed on enhancing regions and non-enhancing peritumoral regions. The mean and the fifth and 95th percentile values of each parameter were compared between PCNSLs and GBMs. The area under the receiver operating characteristic curve (AUC) values were used to compare the discriminating performances among the indices. RESULTS: In enhancing regions, the mean and fifth and 95th percentile values of ADC44.5 ms and ADC7.1 ms in PCNSLs were significantly lower than those in GBMs (p = 0.02 for 95th percentile of ADC44.5 ms, p = 0.04 for ADC7.1 ms, and p < 0.01 for others). Furthermore, the mean and fifth and 95th percentile values of cADC and rcADC were significantly higher in PCNSLs than in GBMs (each p < 0.01). The AUC of the best-performing index for ADC7.1 ms was significantly lower than that for ADC44.5 ms (p < 0.001). The mean rcADC showed the highest discriminating performance (AUC = 0.920) among all indices. In peritumoral regions, no significant difference in any of the three indices of ADC44.5 ms, ADC7.1 ms, cADC, and rcADC was observed between PCNSLs and GBMs. CONCLUSIONS: Effective diffusion time setting can have a crucial impact on the performance of ADC in differentiating between PCNSLs and GBMs. The time-dependent diffusion MRI parameters may be useful in the differentiation of these lesions.

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 on the image quality of modified reduced field-of-view diffusion-weighted magnetic resonance imaging of pancreatic adenocarcinoma using spatially tailored two-dimensional radiofrequency pulses with a tilted excitation plane: A comparison with conventional field-of-view imaging.

PURPOSE: Modified reduced FOV diffusion-weighted imaging (DWI) using spatially-tailored 2D RF pulses with tilted excitation plane (tilted r-DWI) has been developed. The purpose of this study was to evaluate the impact on image quality and quantitative apparent diffusion coefficient (ADC) values of tilted r-DWI for pancreatic ductal adenocarcinomas (PDAC) in comparison to conventional full-FOV DWI (f-DWI). METHODS: This retrospective study included 21 patients (mean 70.7, range 50-85 years old) with pathologically confirmed PDAC. All MR images were obtained using 3 T systems. Two radiologists evaluated presence of blurring or ghost artifacts, susceptibility artifacts, and aliasing artifacts; anatomic visualization of the pancreas; interslice signal homogeneity; overall image quality; and conspicuity of the PDAC. For quantitative analysis, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), signal-intensity ratio (SIR) and ADC values were measured using regions of interest. RESULTS: All image quality scores except aliasing artifacts in tilted r-DWI were significantly higher than those in f-DWI (p < 0.01). The CNR and SIR of PDAC were significantly higher in tilted r-DWI than in f-DWI (6.7 ± 4.4 vs. 4.7 ± 3.9, 2.02 ± 0.72 vs. 1.72 ± 0.60, p < 0.01). Conversely, the SNR of PDAC in tilted r-DWI was significantly lower than that in f-DWI (56.0 ± 33.1 vs. 113.6 ± 67.3, p < 0.01). No significant difference was observed between mean ADC values of the PDAC calculated from tilted r-DWI (tilted r-ADC) and those from f-DWI (f-ADC) (1225 ± 250 vs. 1294 ± 302, p = 0.11). CONCLUSION: The r-DWI using 2D RF techniques with a tilted excitation plane was shown to significantly improve the image quality and CNR and reduce image artifacts compared to f-DWI techniques in MRI evaluations of PDAC without significantly affecting ADC values.

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.

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.

A case of carcinoid syndrome probably exacerbated by hemodialysis in which prochlorperazine maleate was effective.

Carcinoid syndrome is caused by the release of serotonin and other substances, which commonly occurs due to liver metastasis of neuroendocrine tumors. It rarely occurs due to liver metastasis of neuroendocrine carcinoma. We report the case of a patient with liver metastasis of neuroendocrine carcinoma who suffered from acute abdominal pain and diarrhea triggered by hemodialysis. Various differential diagnoses were considered, but we concluded these symptoms to be probably caused by exacerbation of carcinoid syndrome, as the serum 5HIAA level was markedly elevated, and a drug with anti-serotonin activity was effective. Prochlorperazine maleate, which has anti-serotonin activity, was effective for these symptoms, and the patient was able to continue maintenance hemodialysis, which contributed to his quality of life and prognosis. We speculated the mechanism of carcinoid exacerbation was that substances such as serotonin had entered the systemic circulation via the increased extrahepatic shunt of the portal venous blood flow, entering the inferior vena cava and that this condition had been triggered by hemodialysis via the same mechanism as portal systemic encephalopathy.

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.

Differentiating brain metastasis from glioblastoma by time-dependent diffusion MRI.

BACKGROUND: This study was designed to investigate the use of time-dependent diffusion magnetic resonance imaging (MRI) parameters in distinguishing between glioblastomas and brain metastases. METHODS: A retrospective study was conducted involving 65 patients with glioblastomas and 27 patients with metastases using a diffusion-weighted imaging sequence with oscillating gradient spin-echo (OGSE, 50 Hz) and a conventional pulsed gradient spin-echo (PGSE, 0 Hz) sequence. In addition to apparent diffusion coefficient (ADC) maps from two sequences (ADC50Hz and ADC0Hz), we generated maps of the ADC change (cADC): ADC50Hz - ADC0Hz and the relative ADC change (rcADC): (ADC50Hz - ADC0Hz)/ ADC0Hz × 100 (%). RESULTS: The mean and the fifth and 95th percentile values of each parameter in enhancing and peritumoral regions were compared between glioblastomas and metastases. The area under the receiver operating characteristic curve (AUC) values of the best discriminating indices were compared. In enhancing regions, none of the indices of ADC0Hz and ADC50Hz showed significant differences between metastases and glioblastomas. The mean cADC and rcADC values of metastases were significantly higher than those of glioblastomas (0.24 ± 0.12 × 10-3mm2/s vs. 0.14 ± 0.03 × 10-3mm2/s and 23.3 ± 9.4% vs. 14.0 ± 4.7%; all p < 0.01). In peritumoral regions, no significant difference in all ADC indices was observed between metastases and glioblastomas. The AUC values for the mean cADC (0.877) and rcADC (0.819) values in enhancing regions were significantly higher than those for ADC0Hz5th (0.595; all p < 0.001). CONCLUSIONS: The time-dependent diffusion MRI parameters may be useful for differentiating brain metastases from glioblastomas.

Enhanced PD-L1 expression on tumor cells in primary CD30-positive cutaneous large T-cell lymphoma: a report of lymph node lesions of four cases.

Scarce data are available regarding neoplastic PD-L1 (nPD-L1, clone SP142) expression in cutaneous T-cell lymphoma. We recently documented a possible association of increased nPD-L1 expression with tumor progression to secondary nodal involvement in two cases of CD30-positive primary cutaneous large T-cell lymphoma (PC-LTCL) (Pathol Int 2020;70:804). Notably, the nodal sites exhibited classic Hodgkin lymphoma (CHL) mimicry related to both morphology and tumor microenvironment (TME), i.e., abundant PD-L1-positive tumor-associated macrophages and low-level PD-1 expression on T-cells. Immunohistochemistry highlighted distinctly different nPD-L1 positivity between the cutaneous and nodal lesions. In the present study, we aimed to validate this unique phenomenon in a larger series of four cases with FISH and targeted-capture sequencing (targeted-seq) analysis. We retrospectively identified two more cases of CD30-positive PC-LTCL with secondary nodal involvement among all patients consecutively diagnosed between 2001-2021. All cases immunohistochemically exhibited elevated nPD-L1 expression on ≥50% of lymphoma cells in nodal tumors, clearly contrasting with the scarce nPD-L1 positivity (≤1%) in cutaneous tumors. Moreover, all nodal lesions exhibited CHL-like TME, with abundant PD-L1-positive tumor-associated macrophages and low-level PD-1 expression on T cells, although the CHL-like morphology was limited in the two original cases. None showed CD274/PD-L1 copy number alteration by FISH analysis, or structural variations of PD-L1 3'-UTR by targeted-seq analysis. These findings indicated that nPD-L1 expression is linked with tumor progression and CHL-like TME in nodal involvement of PC-LTCL. Interestingly, one autopsied case exhibited heterogeneity of nPD-L1 expression at different disease sites.

Continuous High Positive-End Expiratory Pressure May Worsen Renal Function in Patients With Acute Respiratory Distress Syndrome: Retrospective Analyses of a Nationwide, Multicenter Observational Study in Japan.

BACKGROUND: Positive end-expiratory pressure (PEEP), especially continuous high PEEP, is thought to be a risk factor for worsening renal function (WRF) due to impaired venous return and the development of renal interstitial edema. In this study, we investigated whether PEEP is a risk factor for WRF in patients with acute respiratory distress syndrome (ARDS), a representative pathology that requires continuous high PEEP for respiratory management. METHODS: We performed retrospective sub-analyses of the Japanese Association for Acute Medicine, a nationwide prospective observational registry of ARDS (FORECAST ARDS registry) prospective multicenter cohort study. WRF was defined on the basis of a worsening renal Sequential Organ Failure Assessment (SOFA) score. We performed univariate and multivariable analyses to identify possible risk factors for WRF, and propensity score analyses to compare the frequency of WRF according to cutoff values for the difference in PEEP between day 1 and day 4. RESULTS: We analyzed 151 cases. Multivariable analysis showed that the difference in PEEP (odds ratio (OR) 1.123 (95% confidence interval (CI) 1.017-1.240), P = 0.022) and male sex (OR 3.287 (95% CI 1.029-10.502), P = 0.045) were risk factors for WRF. Propensity score analysis showed trends towards an increased risk for WRF in each cutoff value for the difference in PEEP: -5 cmH2O (OR 0.389 (95% CI 0.084-1.799), P = 0.229), 0 cmH2O (OR 2.222 (95% CI 0.755-6.540), P = 0.150), and 5 cmH2O (OR 3.277 (95% CI 0.940-11.425), P = 0.065). CONCLUSIONS: This study revealed that the difference in PEEP between days 1 and 4 was positively associated with WRF. However, a significant cutoff value for the difference in PEEP was not determined.

Breath-hold High-resolution T1-weighted Gradient Echo Liver MR Imaging with Compressed Sensing Obtained during the Gadoxetic Acid-enhanced Hepatobiliary Phase: Image Quality and Lesion Visibility Compared with a Standard T1-weighted Sequence.

PURPOSE: To evaluate the feasibility of breath-hold (BH) high-resolution (HR) T1-weighted gradient echo hepatobiliary phase (HBP) imaging using compressed sensing (CS) in gadoxetic acid-enhanced liver MRI in comparison with standard HBP imaging using parallel imaging (PI). METHODS: The study included 122 patients with liver tumors with hypointensity in the HBP who underwent both HR HBP imaging with CS and standard HBP imaging with PI. Two radiologists evaluated the liver edge sharpness, hepatic vessel conspicuity, bile duct conspicuity, image noise, and overall image quality, as well as the lesion conspicuity on HR and standard HBP imaging and the contrast-enhanced (CE) MR cholangiography (MRC) image quality reconstructed from HBP images. As a quantitative analysis, the SNR of the liver and the liver to lesion signal intensity ratio (LLSIR) were also determined. RESULTS: The liver edge sharpness, hepatic vessel conspicuity, bile duct conspicuity, and overall image quality as well as the lesion conspicuity and the LLSIR on HR HBP imaging with CS were significantly higher than those on standard HBP imaging (all of P < 0.001). The image quality of CE-MRC reconstructed from HR HBP imaging with CS was also significantly higher than that from standard HBP imaging (P < 0.001). Conversely, the SNR of liver in standard HBP was significantly higher than that in HR HBP with CS (P < 0.001). CONCLUSION: BH HR HBP imaging with CS provided an improved overall image quality, lesion conspicuity, and CE-MRC visualization when compared with standard HBP imaging without extending the acquisition time.

Impact of Extracorporeal Membrane Oxygenation in an Infant Treated with Vancomycin: A Case Report.

Vancomycin is a glycopeptide antibiotic used for prophylaxis and treatment of infections caused by methicillin-resistant Staphylococcus aureus. Although major organ sizes and functions mature during infancy, pharmacokinetic studies, especially those focused on infants, are limited. Changes in extracorporeal membrane oxygenation-related drug disposition largely contribute to changes in pharmacokinetics. Here, pharmacokinetic profiles of vancomycin in an infant receiving extracorporeal membrane oxygenation therapy are presented. A two-month-old Japanese infant with moderately decreased renal function was started on 12.0 mg/kg vancomycin every 8 h from day X for prophylaxis of pneumonia during extracorporeal membrane oxygenation therapy. As the trough concentration of vancomycin observed on day X+3 was 27.1 µg/mL, vancomycin was then discontinued. The trough concentration decreased to 18.6 µg/mL 24 h after discontinuation, and 9.0 mg/kg vancomycin every 12 h was restarted from day X+5. On day X+6, the trough concentration increased to 36.1 µg/mL, and vancomycin therapy was again discontinued. On day X+7, the trough concentration decreased to 22.4 µg/mL. The pharmacokinetic profiles of vancomycin based on first-order conditional estimation in this infant were as follows: plasma clearance = 0.053 L/kg/hour, distribution volume = 2.19 L/kg, and half-life = 29.5 h. This research reported the prolonged half-life of vancomycin during extracorporeal membrane oxygenation in infants with moderately decreased renal function.

A Scoring System for Anterior Longitudinal Ligament Ossification of the Lumbar Spine in Diffuse Idiopathic Skeletal Hyperostosis: Relationship Between the Extent of Ligament Ossification and the Range of Motion.

STUDY DESIGN: Retrospective observational study. OBJECTIVE: To investigate the relationship between the extent of ligament ossification and the range of motion (ROM) of the lumbar spine and develop a new scoring system. METHODS: Forty-three patients (30 men and 13 women) with lumbar spinal canal stenosis who underwent decompression from January to December 2018. Ligament ossification at L1/2 to L5/S was assessed on plain X-ray (Xp) and computed tomography (CT) using a modified Mata scoring system (0 point: no ossification, 1 point: ossification of less than half of the intervertebral disc height, 2 points: ossification of half or more of the intervertebral disc height, 3 points: complete bridging), and the intra-rater and inter-rater reliability of the scoring was assessed. The relationship of the scores with postoperative lumbar ROM was investigated. RESULT: Intra-rater reliability was high (Cronbach's α was 0.74 for L5/S on Xp but 0.8 or above for other sections), as was inter-rater reliability (Cronbach's α was 0.8 or above for all the segments). ROM significantly decreased as the score increased (scores 1 to 2, and 2 to 3). A significant moderate negative correlation was found between the sum of the scores at L1/2-L5/S and the ROM at L1-S (ρ = - 0.4493, P = 0.025). CONCLUSION: Our scoring system reflects lumbar mobility and is reproducible. It is effective for assessing DISH in fractures and spinal conditions, and monitoring effects on treatment outcomes and changes over time.

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.

Sequestration of Antimicrobial Agents in Xcoating and Heparin-Coated Extracorporeal Membrane Oxygenation Circuits: An In Vitro Study.

Limited data exist to guide antimicrobial therapy commonly prescribed to patients undergoing extracorporeal membrane oxygenation (ECMO). This study aimed to describe the kinetics of the cefazolin, doripenem, daptomycin, and levofloxacin in heparin-coated and Xcoating ECMO circuits. Circuits were primed with bovine whole blood and maintained at a physiological pH and temperature for 24 h. Each antimicrobial agent was added to the whole blood before priming. Equivalent doses of these drugs were added to glass jars containing fresh bovine whole blood as a control. Serial blood samples were collected from the ECMO circuits and controls over 24 h, and drug concentrations were quantified using validated assays. The concentrations of cefazolin, doripenem, daptomycin, and levofloxacin did not decrease significantly over 24 h. Collectively, these antimicrobial agents can be administered without the need to consider sequestration when using either heparin-coated or Xcoating circuits.

Subcutaneous Panniculitis-like T-cell Lymphoma with a HAVCR2 Mutation Diagnosed after 10 Years of Treatment with Glucocorticoids and Cyclosporine as Lupus Panniculitis.

Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is a very rare cutaneous T cell lymphoma that has been reported to be associated with autoimmune disorders but is most commonly associated with systemic lupus erythematosus. We herein report a 26-year-old man thought to have lupus panniculitis (LP) treated for 10 years with corticosteroids and cyclosporine. After several relapses with panniculitis, he was finally diagnosed with SPTCL, which was confirmed to have a HAVCR2 mutation for p.Tyr82Cys. We emphasize that rheumatologists should be aware of the possibility of SPTCL, despite its rare appearance, when making a diagnosis of LP or when encountering clinical manifestations that are not consistent with LP.

Combined use of pathological and genomic alteration analyses for the diagnosis of gray zone lymphoma.

Histiocytic sarcoma (HS) is a rare malignancy showing morphologic and immunophenotypic features of histiocytes. HS has morphologic overlap with many other diseases, including various kinds of lymphomas. Gray zone lymphoma (GZL) is a rare B-cell lymphoma subtype characterized by overlapping features between diffuse large B-cell lymphoma and classic Hodgkin lymphoma. The histologic overlap with other diverse diseases of HS and the pathological diversity of GZL make it difficult to render a diagnosis. A 44-year-old woman who was initially diagnosed with HS was diagnosed with GZL after reexamination, including a genetic alteration test. After 6 cycles of brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine, she achieved a complete response. Genomic alteration assessment may be useful for the accurate diagnosis of malignant lymphomas, which are difficult to diagnose, such as GZL.

Psoriatic arthritis successfully treated with second-line anti-interleukin-6 treatment: a case report and review of the literature.

BACKGROUND: Psoriatic arthritis treatment with antitumor necrosis factor has been shown to reduce disease activity. Nonetheless, more than 30% of patients do not achieve a sufficient response to tumor necrosis factor blockers. Currently, treatment with interleukin-6 inhibitors is expected to be effective and suppress the joint destruction in patients with psoriatic arthritis; however, evidence regarding their efficacy is limited to a few reports. CASE PRESENTATION: A 78-year-old Japanese woman with psoriatic arthritis associated with rapid joint destruction was successfully treated with a second-line anti-interleukin-6 receptor agent. In this case, a tumor necrosis factor inhibitor induced an inadequate response, and the right knee and left hip joints required artificial joint replacement surgery. However, second line treatment with anti-interleukin-6 treatment was effective, and the right elbow joint function was preserved. CONCLUSIONS: We experienced a case of psoriatic arthritis, in which anti-interleukin-6 treatment repaired a bone cyst in the lateral epicondyle of the humerus and enthesitis of the distal interphalangeal joints. The patient is currently in clinical remission with no restrictions in daily life activities. Anti-interleukin-6 treatment may address the unmet needs of patients with psoriatic arthritis who are resistant or intolerant to antitumor necrosis factor treatment, with rapidly destructive large joints but with well-managed skin manifestations.