The usefulness of contrast-enhanced subtraction magnetic resonance imaging for detecting endoleaks after endovascular aortic repair with prophylactic intraoperative sac embolization.

BACKGROUND: Metallic and hyperdense artifacts and T1-shortening substances in the abdominal aortic aneurysm (AAA) sac generated by embolic materials and lipiodol pose challenges in the identification of endoleaks on follow-up computed tomography (CT) or magnetic resonance imaging (MRI). PURPOSE: To evaluate the usefulness of contrast-enhanced subtraction MRI (CES-MRI) for detecting endoleaks after endovascular abdominal aortic aneurysm repair (EVAR) with intraoperative AAA sac embolization compared with CE-CT, this study was conducted. MATERIAL AND METHODS: In this study, 28 consecutive patients who underwent EVAR with prophylactic AAA sac embolization were included. All patients underwent CES-MRI and CE-CT to detect endoleaks. The definitive diagnosis of endoleaks was a consensus reading of CE-CT and CES-MRI by two certified radiologists, in addition to angiography or reproducible radiological findings in the observational examination. Analysis was performed to evaluate which examination was better for detecting endoleaks. RESULTS: The sensitivity, specificity, and area under the curve of CE-CT and CES-MRI according to observer 1 were 50%, 100%, and 0.813 (95% confidence interval [CI] = 0.625-1.00) and 100%, 95%, and 0.997 (95% CI = 0.984-1.00), respectively, and those according to observer 2 were 50%, 100%, and 0.750 (95% CI = 0.514-0.986) and 100%, 95%, and 0.969 (95% CI = 0.903-1.00), respectively. Intolerable artifacts were significantly observed on CE-CT. The severity of the artifacts did not depend on the stent graft on CT and MRI. CONCLUSION: Although no significant difference was observed, CES-MRI tended to have better accuracy for endoleak detection in EVAR with intraoperative AAA sac embolization than CE-CT.

Development of bacteriostatic central venous port using photobiomodulation: a comparative in vitro study.

Photobiomodulation (PBM) occurs when a cell is exposed to low energy intensities. A novel central venous port (CVP) with light-emitting diodes (LEDs) that emits red light with a wavelength of 680 nm via wireless energy transmission technology has been established. This comparative in vitro study examined whether PBM can reduce the growth of methicillin-resistant Staphylococcus aureus (MRSA), a common cause of central venous (CV) infections, in vitro. In this comparative in vitro study, the red light with a wavelength of 680 nm was used to irradiate an MRSA suspension in phosphate-buffered saline for 7.5, 15, 30, or 60 min in a 3.5 cm Petri dish with an area of 8.5 cm2. The total energy was 85 J at 7.5 min, 170 J at 15 min, 340 J at 30 min, and 680 J at 60 min. Six dishes for each time and 6 temperature-controlled samples were prepared. Each sample was incubated overnight at 37℃. The Shapiro-wilk test was used to determine whether the data were normally distributed. The numbers of colonies were counted and compared using one-factor ANOVA and Bonferroni's post-hoc test. The mean numbers of colonies in the control group were 60.3, where the numbers of colonies in the irradiated group were 51.4 at 7.5 min, 53.5 at 15 min, 44.6 at 30 min, 34.3 at 60 min. The mean number of colonies in the 60 min irradiated group differed significantly from that in the control, 7.5 min, and 15 min groups. The Bonferroni's post-hoc test showed significant difference in the number of colonies between control vs. 30 min control vs. 60 min, 7.5 min vs. 60 min, 15 min vs. 60 min. PBM with 680 nm LEDs on MRSA for 340 J at 30 min and 680 J at 60 min inhibited the growth of cell colonies. These findings support the use of photobiomodulation in Central venous port to prevent CV access port-Blood stream infection.

PET/CT findings and dose distribution during radiotherapy in T1N0M0-T2N0M0 glottic cancer.

OBJECTIVE: To investigate the positron emission tomography/computed tomography (PET/CT) findings of T1/T2N0M0 glottic cancer (hereafter referred to as T1/T2) and dose distribution in radiotherapy. SUBJECTS AND METHODS: We retrospectively collected data from patients diagnosed with T1/T2N0M0 glottic cancer who received radiotherapy. The extent of fluorine-18-fluorodeoxyglucose (18F-FDG) accumulation in primary tumors, maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), tumor volume of primary tumors on PET/CT were compared. Furthermore, the tumor identified on PET/CT was incorporated into the radiotherapy plans. A dummy plan (radiation field 6x6cm, prescription point facing the vertebral body, maximum dose ≤107%, T1/T2 66Gy/33 fractions) was developed for three-dimensional conformal radiotherapy, and the dose distribution of primary tumors was calculated. RESULTS: Twenty-nine patients (27 men and two women) were included; their mean age was 67.2±15.0 years. Increased 18F-FDG accumulation in primary tumors was observed on PET/CT in 22/29 (78.5%; T1: 14/21 [67%], T2: 8/8 [100%]) patients. The median SUVmax, TLG, and primary tumor volume were significantly different between T1 and T2 (SUVmax, T1: 4.56 vs. T2: 8.43, P=0.035; TLG, T1: 1.01 vs. T2: 3.71 SUVxmL, P<0.01; primary tumor volume, T1: 0.38mL vs. T2: 0.80mL, P=0.01). At a TLG cut-off value of 3.470, the area under the curve was 0.875, sensitivity was 0.875, and specificity was 0.929 for T1-T2 differentiation. In 20 patients with 18F-FDG accumulation, the minimum radiation dose was significantly different between T1 and T2 (66Gy vs. 64Gy, P<0.01) at the same 66Gy prescription. The minimum radiation dose and primary tumor volume show the correlation value (r=-0.516, P=0.02). CONCLUSION: In glottic cancer, T1 and T2 can be differentiated by the extent of 18F-FDG accumulation in primary tumors on PET/CT. The minimum radiation dose rate decreases as volume increases.

Development and Experimental Study of a Polytetrafluoroethylene-Tipped Microcatheter Poorly Adhesive to n-Butyl-2-Cyanoacrylate.

PURPOSE: We have developed a new microcatheter (designated "NSX") with an outer layer of polytetrafluoroethylene (PTFE) at its tip. We compared the adhesion of the new NSX microcatheter and a conventional microcatheter with n-butyl-2-cyanoacrylate (NBCA) in vitro and in swine blood vessels. MATERIALS AND METHODS: The 3 cm tip of the NSX microcatheter is composed of PTFE, which can be identified by double platinum markers. The tips of the NSX and conventional microcatheters were inserted into a vascular model filled with porcine blood with no flow, and NBCA mixed with lipiodol (1:2) was injected from the microcatheters. Two minutes after the injection of NBCA, the microcatheter was withdrawn and the degree of its adhesion to NBCA was evaluated by measuring the resistance value (N) during catheter removal with a digital force gauge. These measurements were repeated with 20 catheters of each type. Similarly, 5 injections were performed with both the NSX and conventional microcatheters in swine vessels. The degree of adhesion of the catheter and blood vessel was evaluated by 2 radiologists under X-ray fluoroscopy on a 3-point scale: 1, no adhesion; 2, mild adhesion; 3, strong adhesion. RESULTS: The mean resistance values (N) for the NSX and conventional microcatheters were 0.503±0.186 and 1.051±0.367 (N), respectively (p<0.001). The NSX adhered negligibly to the NBCA and was easily removed, whereas the conventional microcatheter adhered strongly to the NBCA in the blood vessels and was difficult to remove from the swine vessels (p=0.008). CONCLUSIONS: The new NSX microcatheter with a PTFE tip exhibits poorer adhesion to NBCA than do conventional microcatheters and allows for safer injection of NBCA than conventional microcatheters, without requiring immediate catheter retrieval. CLINICAL IMPACT: The NSX microcatheter with a PTFE tip adheres less strongly to NBCA than do conventional microcatheters and allows the safe injection of NBCA. The NSX microcatheter has double platinum markers on its tip, which make it easy to distinguish the PTFE-covered region. As the NSX does not adhere firmly to the arterial wall, it is less likely to cause vascular injury during removal of the catheter compared with conventional microcatheters, so there is no need to remove the NSX immediately after injecting NBCA. Even operators unfamiliar with NBCA can use NBCA safely with this new NSX microcatheter without requiring special training or skill.

Tumor steatosis and glutamine synthetase expression in patients with advanced hepatocellular carcinoma receiving atezolizumab plus bevacizumab therapy.

AIM: The anti-programmed death-ligand 1 antibody atezolizumab and vascular endothelial growth factor-neutralizing antibody bevacizumab in combination (Atezo + Bev) have become the first-line therapy in advanced hepatocellular carcinoma (HCC). Distinct types of tumor immune microenvironment (TIME) and their associations with specific molecular subclasses and driver gene mutations have been identified in HCC; however, these insights are mainly based on surgically resected early-stage tumors. The current study aimed to reveal the biology and TIME of advanced HCC and their significance in predicting clinical outcomes of Atezo + Bev therapy. METHODS: Thirty-three patients with advanced HCC who were scheduled for treatment with Atezo + Bev therapy were included in this study. Pretreatment tumor biopsy, pre- and posttreatment diffusion-weighted magnetic resonance imaging (MRI) with nine b values (0-1500 s/mm2 ), and other clinicopathologic factors were analyzed. RESULTS: Compared with resectable HCC, advanced HCC was characterized by higher proliferative activity, a higher frequency of Wnt/ß-catenin-activated HCC, and lower lymphocytic infiltration. Prognostically, two metabolism-related factors, histopathologically determined tumor steatosis and/or glutamine synthetase (GS) expression, and MRI-determined tumor steatosis, were the most significant prognostic indicators for progression-free survival (PFS) and overall survival after Atezo + Bev therapy. Furthermore, changes in the pre- and posttreatment true diffusion coefficients on MRI, which might reflect changes in TIME after treatment, were significantly associated with better PFS. CONCLUSIONS: The biology and TIME of HCC were strikingly different in advanced HCC compared with those of surgically resected HCC. Two metabolism-related factors, pathologically determined tumor steatosis and/or GS expression, and MRI-determined tumor steatosis, were found to be the most significant prognostic indicators for Atezo + Bev therapy in advanced HCC.

Clinical value of minimum apparent diffusion coefficient for prediction of clinically significant prostate cancer in the transition zone.

BACKGROUND: This study investigated the association between apparent diffusion coefficients in Prostate Imaging Reporting and Data System 4/5 lesions and clinically significant prostate cancer in the transition zone. METHODS: We included 102 patients who underwent transperineal cognitive fusion targeted biopsy for Prostate Imaging Reporting and Data System 4/5 lesions in the transition zone between 2016 and 2020. The association between apparent diffusion coefficients and prostate cancers in the transition zone was analyzed. RESULTS: The detection rate of prostate cancer was 49% (50/102), including clinically significant prostate cancer in 37.3% (38/102) of patients. The minimum apparent diffusion coefficients in patients with clinically significant prostate cancer were 494.5 ± 133.6 µm2/s, which was significantly lower than 653.8 ± 172.5 µm2/s in patients with benign histology or clinically insignificant prostate cancer. Age, prostate volume, transition zone volume, and mean and minimum apparent diffusion coefficients were associated with clinically significant prostate cancer. Multivariate analysis demonstrated that only the minimum apparent diffusion coefficient value (odds ratio: 0.994; p < 0.001) was an independent predictor of clinically significant prostate cancer. When the cutoff value of the minimum apparent diffusion coefficient was less than 595 µm2/s, indicating the presence of prostate cancer in the transition zone, the detection rate increased to 59.2% (29/49) in this cohort. CONCLUSION: The minimum apparent diffusion coefficient provided additional value to indicate the presence of clinically significant prostate cancer in the transition zone. It may help consider the need for subsequent biopsies in patients with Prostate Imaging Reporting and Data System 4/5 lesions and an initial negative targeted biopsy.

Application of wireless energy transmission technology into central venous ports with light-emitting diodes.

Implantable central venous (CV) ports are widely used for chemotherapy and parenteral nutrition. Generally, CV ports are used safely; however, some patients suffer from drug leakage around the port septum due to mispuncture. Therefore, we developed a CV port that is visible under the skin. We created a prototype of a CV port using a 3D printer. Three red light-emitting diodes (LEDs) were attached around the septum that made the puncture site visible by applying wireless energy transmission technology using electromagnetic resonance. The CV port was implanted under the skin of pork rose meat. The thickness of the skin of pork loin was measured. Fifteen medical doctors participated in the study to visually confirm the lighted CV port. The visibility of the center of the septum with and without lights was scored 0 as non-diagnostic; 1, slightly visible; 2, well visible; and 3, obviously visible. The visibility with or without lights was assessed. The relationship between the years of experience and the visibility score was assessed. The Wilcoxon test was used for statistical analysis. LEDs were easily transmitted through the skin of pork rose meat. The median visibility scores with or without lights were 2 (range, 1-3) and 3 (range, 1-3), respectively (p = 0.005). No significant relationship was found between experience and visibility score (p = 0.289). CV ports with LEDs can be easily recognized compared with those without LEDs. This technique may contribute to medical safety by improving its visibility to avoid mispuncture.

Association between longitudinal changes in striatal dopamine transporter uptake and clinical features of dementia with Lewy bodies.

BACKGROUND: It is widely known that there is low striatal 123 I-2ß-Carbomethoxy-3ß-(4-iodophenyl)-N-(3- fluoropropyl) nortropane (123 I-FP-CIT) dopamine transporter single photon emission tomography (DaT-SPECT) uptake in patients with dementia with Lewy bodies (DLB). No studies to date have analyzed the association between longitudinal changes of clinical features and DaT uptake in patients with Parkinson syndrome, particularly those with DLB. The aim of this study was to investigate the association between the longitudinal changes in DaT uptake and the severity of parkinsonism and cognitive function in DLB patients. METHODS: A total of 35 outpatients with probable DLB who underwent DaT-SPECT twice (at the initial examination and the follow-up period) in the Memory Disorder Clinic at the Department of Geriatric Medicine, Tokyo Medical University, were enrolled in this study between April 2014 and September 2020. The correlation between annual changes in DaT uptake and clinical features (cognitive function decline and parkinsonism) of the patients was analyzed. RESULTS: A significant correlation was detected between annual changes in parkinsonism symptom severity and DaT uptake in the left posterior putamen (r = -0.39, P = 0.03), and between Mini-Mental State Examination scores and DaT uptake in all regions except the right posterior putamen (P < 0.05) in patients with DLB. CONCLUSIONS: Our results suggested that the pathway from the ventrolateral tier of the substantia nigra to the putamen might be more crucial for motor function than other pathways, not only in Parkinson's disease but also in DLB.

Comparison of modified CEUS LI-RADS with sonazoid and CT/MRI LI-RADS for diagnosis of hepatocellular carcinoma.

AIM: To compare the diagnostic performance based on the modified CEUS Liver Imaging Reporting and Data System (LI-RADS), which includes Kupffer-phase findings as a major imaging feature, with that of CT and MRI (CT/MRI) LI-RADS for liver nodules in patients at high risk of HCC. METHODS: A total of 120 patients with 120 nodules were included in this retrospective study. The median size of the lesions was 20.0 mm (interquartile range, 14.0-30.8 mm). Of these lesions, 90.0% (108 of 120) were confirmed as HCCs, 6.7% (8 of 120) were intrahepatic cholangiocarcinomas, 1.7% (2 of 120) were metastases, and 1.7% (2 of 120) were dysplastic nodules. All nodules were diagnosed histopathologically. Each nodule was categorized according to the modified CEUS LI-RADS and CT/MRI LI-RADS version 2018. The diagnostic performance and inter-modality agreement of each criterion was compared. RESULTS: The inter-modality agreement for the modified CEUS LI-RADS and CT/MRI LI-RADS was slight agreement (kappa = 0.139, p = 0.015). The diagnostic accuracies of HCCs for the modified CEUS LR-5 and CT/MRI LR-5 were 70.0% (95% confidence interval [CI]: 61.0%, 78.0%) versus 70.8% (95% CI: 61.8%, 78.8%) (p = 0.876), respectively. The diagnostic accuracies of non-HCC malignancies for the modified CEUS LR-M and CT/MRI LR-M were 84.2% (95% CI: 76.4%, 90.2%) versus 96.7% (95% CI: 91.7%, 99.1%) (p = 0.002), respectively. CONCLUSIONS: The diagnostic performance for HCCs on the modified CEUS LR-5 and CT/MRI LR-5 are comparable. In contrast, CT/MRI LR-M has better diagnostic performance for non-HCC malignancy than that of the modified CEUS LR-M.

Sarcopenia at the infrahyoid level as a prognostic factor in patients with advanced-stage non-virus-related head and neck carcinoma.

PURPOSE: The purpose of this study was to assess whether the infrahyoid skeletal muscle index (IHSMI) can be used instead of the L3 skeletal muscle index (L3SMI) to define sarcopenia and predict prognosis in patients with locally advanced head and neck squamous cell carcinoma (LHNSCC). METHODS: Patients treated for LHNSCC between January 2009 and April 2018 were assessed. The muscular area at the L3 transverse process and infrahyoid was contoured on absorption-corrected computed tomography prior to treatment. Sarcopenia based on L3SMI (S-L) was defined as values of < 52.4 cm2/m2 for men and < 38.5 cm2/m2 for women. Sarcopenia based on IHSMI (S-I) was determined via receiver operating curve analysis. Overall survival (OS) and cause-specific survival (CSS) curves were constructed using the Kaplan-Meier method. RESULTS: In total, 101 patients were analyzed. The median follow-up period was 19 months (range 3-101 month). S-L and S-I were identified in 74 (73.3%) and 56 patients (55.4%), respectively. The 5-year OS rate did not differ between patients with and without S-L (64.9% vs. 79.2%, p = 0.635), whereas the rate was lower in patients with S-I than without S-I (57.1% vs. 93.0%, p = 0.006). Similarly, the 5-year CSS rate did not differ between patients with and without S-L (77.0% vs. 82.3%, p = 0.523), but the rate was lower in patients with S-I (61.2% vs. 93.0%, p = 0.02). CONCLUSION: Pretreatment S-I, but not S-L, was a good predictor of OS and CSS in patients with LHNSCC.

Morphological changes of the thyroid gland as a new radiographic marker for lung cancer treatment efficacy of immune checkpoint inhibitors.

BACKGROUND: Fully human IgG4 programmed cell death-1 (PD-1) immune checkpoint inhibitors are effective against non-small-cell lung cancer (NSCLC). PD-1-targeted antibodies induce autoimmune adverse events that are not caused by conventional chemotherapy. PURPOSE: To clarify the association between morphological changes of the thyroid gland and the efficacy of PD-1 immune checkpoint inhibitor treatment for lung cancer. MATERIAL AND METHODS: The study enrolled 29 patients who received PD-1 immune checkpoint inhibitor treatment. The thyroid volume was measured using computed tomography (CT) at the following three timepoints: pre-treatment (baseline); three months after the initial administration (early treatment); and at the last CT scan during the observation period (late treatment). Thyroid volume ratios were calculated as follows: early treatment/baseline thyroid volume at CT (E/B-CT ratio) and late treatment/baseline thyroid volume at CT (L/B-CT ratio). Thyroid dysfunction was assessed according to thyroid hormone levels. RESULTS: The E/B-CT ratio was significantly higher in patients with adverse events of grade 3 or higher than in the other patients (P = 0.013). The L/B-CT ratio was significantly lower in patients with thyroid dysfunction than in those without thyroid dysfunction (P = 0.001). Complete response (CR) was achieved in three patients at the time of the final CT. The E/B-CT ratio was significantly higher in patients with CR than in the other patients (1.48 vs. 0.99, P = 0.029). CONCLUSION: Changes in thyroid volume after administration of PD-1 immune checkpoint inhibitors might be a useful radiographic marker of therapeutic efficacy in patients with lung cancer.

Usefulness of texture analysis in 123I-FP-CIT for the differentiation of AD and DLB subtypes.

OBJECTIVE: I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) is well known to be a useful tracer for differentiating dementia with Lewy bodies (DLB) and Alzheimer disease (AD). However, clinically, there are some cases in which these diseases cannot be differentiated by ordinary quantitative methods. Therefore, in this study, we established an index that reflects not only the total count but also the distribution and heterogeneity of tracer uptake. We investigated whether assessment of the heterogeneous depletion of 123I-FP-CIT is useful for the differentiation of various types of dementia, i.e., probable DLB, possible DLB, and AD, using texture analysis. MATERIALS AND METHODS: A total of 122 patients with either probable DLB (n=35), possible DLB (n=23), AD (n=44), and normal controls (n=20) were analyzed. Summated single photon emission computed tomography (SPECT) images (7 to 10 slices) of the patients, including the bilateral striatum, were analyzed using the gray-level histogram method (GLHM) of texture analysis. Mean, variance, skewness, and kurtosis of GLHM were compared with the specific binding ratio by Livia Tossici-Bolt's method (SBR). RESULTS: The sensitivity and specificity for differentiating probable DLB from possible DLB, AD, and normal controls were 97.1% and 77.0%, respectively, for skewness, using a cut-off point of 6.8%, and 97.1% and 81.6%, respectively, for kurtosis, using a cut-off point of 53.4%. The sensitivity and specificity for differentiating probable and possible DLB from AD and normal controls was 65.5% and 98.4%, respectively, for skewness, using a cut-off point of 6.4%, and 79.3% and 93.8%, respectively, for kurtosis, using a cut-off point of 53.4%. CONCLUSION: In the assessment of the efficacy of 123I-FP-CIT to differentiate AD and DLB subtypes, mean, variance, skewness, and kurtosis by GLHM was as useful as the SBR method. Moreover, possible DLB and probable DLB could be differentiated by skewness and kurtosis. Our results demonstrate that texture analysis is more useful than conventional quantitative methods for obtaining valuable information of the brain. Textural features as such may have considerable potential as imaging biomarkers of DLB progression.

Facilitated NaCl Uptake in the Highly Developed Bundle of the Nephron in Japanese Red Stingray Hemitrygon akajei Revealed by Comparative Anatomy and Molecular Mapping.

Batoidea (rays and skates) is a monophyletic subgroup of elasmobranchs that diverged from the common ancestor with Selachii (sharks) about 270 Mya. A larger number of batoids can adapt to low-salinity environments, in contrast to sharks, which are mostly stenohaline marine species. Among osmoregulatory organs of elasmobranchs, the kidney is known to be dedicated to urea retention in ureosmotic cartilaginous fishes. However, we know little regarding urea reabsorbing mechanisms in the kidney of batoids. Here, we performed physiological and histological investigations on the nephrons in the red stingray (Hemitrygon akajei) and two shark species. We found that the urine/plasma ratios of salt and urea concentrations in the stingray are significantly lower than those in cloudy catshark (Scyliorhinus torazame) under natural seawater, indicating that the kidney of stingray more strongly reabsorbs these osmolytes. By comparing the three-dimensional images of nephrons between stingray and banded houndshark (Triakis scyllium), we showed that the tubular bundle of stingray has a more compact configuration. In the compact tubular bundle of stingray kidney, the distal diluting tubule was highly developed and frequently coiled around the proximal and collecting tubules. Furthermore, co-expression of NKAα1 (Na+/K +-ATPase) and NKCC2 (Na+- K+-2Cl- cotransporter 2) mRNAs was prominent in the coiled diluting segment. These findings imply that NaCl reabsorption is greatly facilitated in the stingray kidney, resulting in a higher reabsorption rate of urea. Lowering the loss of osmolytes in the glomerular filtrate is likely favorable to the adaptability of batoids to a wide range of environmental salinity.

Introducing the Amphibious Mudskipper Goby as a Unique Model to Evaluate Neuro/Endocrine Regulation of Behaviors Mediated by Buccal Sensation and Corticosteroids.

Some fish have acquired the ability to breathe air, but these fish can no longer flush their gills effectively when out of water. Hence, they have developed characteristic means for defense against external stressors, including thirst (osmolarity/ions) and toxicity. Amphibious fish, extant air-breathing fish emerged from water, may serve as models to examine physiological responses to these stressors. Some of these fish, including mudskipper gobies such as Periophthalmodon schlosseri, Boleophthalmus boddarti and our Periophthalmus modestus, display distinct adaptational behaviors to these factors compared with fully aquatic fish. In this review, we introduce the mudskipper goby as a unique model to study the behaviors and the neuro/endocrine mechanisms of behavioral responses to the stressors. Our studies have shown that a local sensation of thirst in the buccal cavity-this being induced by dipsogenic hormones-motivates these fish to move to water through a forebrain response. The corticosteroid system, which is responsive to various stressors, also stimulates migration, possibly via the receptors in the brain. We suggest that such fish are an important model to deepen insights into the stress-related neuro/endocrine-behavioral effects.

Regulation of LRG1 expression by RNA-binding protein Puf5 in the budding yeast cell wall integrity pathway.

The PUF RNA-binding protein Puf5 is involved in regulation of the cell wall integrity (CWI) pathway in yeast. Puf5 negatively regulates expression of LRG1 mRNA, encoding for a GTPase-activating protein for Rho1 small GTPase. Here, we further analyzed the effect of Puf5 on LRG1 expression, together with Ccr4 and Pop2 deadenylases, Dhh1 decapping activator, and other PUF proteins. We found that the growth defect of puf5∆ mutant was enhanced by ccr4∆ mutation, which was partially suppressed by LRG1 deletion. Consistently, Lrg1 protein level was much more up-regulated in ccr4Δ puf5Δ double mutant than in each single mutant. Interestingly, LRG1 poly(A) tail length was longer in ccr4∆ mutant but not in puf5∆ mutant. Thus, Puf5 regulates LRG1 expression independently from Ccr4, although Puf5 recruits the Ccr4-Not deadenylase complex for mRNA destabilization. Unexpectedly, puf6Δ mutation suppressed the growth defect caused by ccr4Δ puf5∆ mutation. Loss of Rpl43a and Rpl43b ribosomal proteins, the previously identified Puf6 interactors, also suppressed the growth defect of ccr4Δ puf5Δ mutant. Our results suggest that Puf5 functions in the CWI pathway by regulating LRG1 expression in a deadenylase-independent manner, and that Puf6 is involved in the Ccr4- and Puf5-mediated regulation of cell growth through association with Rpl43.

Irreversible Electroporation versus Radiofrequency Ablation: Comparison of Systemic Immune Responses in Patients with Hepatocellular Carcinoma.

PURPOSE: Irreversible electroporation (IRE) differs from thermal radiofrequency (RF) ablation, especially in terms of the reparative process in the ablation zone induced. To elucidate this, the systemic immune responses after 2 mechanistically different types of ablation (IRE and RF ablation) were evaluated in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Twenty-one patients with HCC who underwent either RF ablation (n = 11) or IRE (n = 10) were studied. Peripheral blood samples were collected from all patients at 4 timepoints: before ablation, within 1 hour after ablation, 1 day after ablation, and 4 days after ablation. The phenotypes and functions of immune cells in peripheral blood and serum levels of cytokines and chemokines were monitored and analyzed using the mixed-effects model. Follow-up radiological images were also obtained to assess temporal changes in the ablation zone. RESULTS: The most significant difference was seen in the levels of macrophage migration inhibitory factor (MIF) in the IRE group compared to the RF ablation group (P = .0011): the serum levels of MIF in the IRE group significantly increased immediately after IRE and then rapidly decreased to the pre-ablation range 1 day after IRE, but, in contrast, no consistent trend was observed in the RF ablation group. The axial diameter (P = .0009) and area (P = .0192) of the ablation zone of IRE were significantly smaller than those of RF ablation 1 year after ablation. CONCLUSIONS: IRE was found to be associated with a significant early increase in MIF levels, which may facilitate the early reparative process and result in significant shrinkage of the ablation zone.

Prediction of high-stage liver fibrosis using ADC value on diffusion-weighted imaging and quantitative enhancement ratio at the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI at 1.5 T.

Background Recently, diffusion-weighted imaging (DWI) and quantitative enhancement ratio measured at the hepatobiliary phase (HBP) of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) has been established as an effective method for evaluating liver fibrosis. Purpose To evaluate which is a more favorable surrogate marker in predicting high-stage liver fibrosis, apparently diffusion coefficient (ADC) value or quantitative enhancement ratio measured on HBP. Material and Methods Eighty-three patients with 99 surgically resected hepatic lesions were enrolled in this study. DWI was performed with b-values of 100 and 800 s/mm2. Regions of interest were set on ADC map, and the HBP of Gd-EOB-DTPA-enhanced MRI, to calculate ADC value, liver-to-muscle ratio (LMR), liver-to-spleen ratio (LSR), and contrast enhancement index (CEI) of liver. We compared these parameters between low-stage fibrosis (F0, F1, and F2) and high-stage fibrosis (F3 and F4). Receiver operating characteristic analysis was performed to compare the diagnostic performance when distinguishing low-stage fibrosis from high-stage fibrosis. Results LMR and CEI were significantly lower at high-stage fibrosis than at the low stage ( P < 0.01 and P = 0.04, respectively), whereas LSR did not show a significant difference ( P = 0.053). No significant difference was observed in diagnostic performance between LMR and CEI ( P = 0.185). The best sensitivity and specificity, when an LMR of 2.80 or higher was considered to be low-stage fibrosis, were 82.4% and 75.6%, respectively. ADC value showed no significant differences among fibrosis grades ( P = 0.320). Conclusion LMR and CEI were both adequate surrogate parameters to distinguish high-stage fibrosis from low-stage fibrosis.

Significance of CD4+ T-cell count in the management of appendicitis in patients with HIV.

SUMMARY: Identification of complicated appendicitis (CA) is critical to the management of appendicitis. However, previous studies have not investigated indicators of CA among patients with HIV or whether it is safe to use conservative treatment for appendicitis in these patients. Among 322 patients with appendicitis, we identified 14 who had HIV. Six of them were operated and 8 were treated with antibiotics; CA was diagnosed in 4. Patients with HIV and CA had a significantly lower CD4+ T-cell count than those with uncomplicated appendicitis. A white blood cell count lower than 7.4 × 10(9)/L was observed exclusively in patients with CA. No patient with HIV whose appendicitis was treated conservatively died or experienced a recurrence. We discuss our findings, which suggest the possibility of conservative treatment of appendicitis in patients with HIV and identification of CA by low CD4+ T-cell count.

Measuring hepatic functional reserve using low temporal resolution Gd-EOB-DTPA dynamic contrast-enhanced MRI: a preliminary study comparing galactosyl human serum albumin scintigraphy with indocyanine green retention.

OBJECTIVE: To investigate if tracer kinetic modelling of low temporal resolution dynamic contrast-enhanced (DCE) MRI with Gd-EOB-DTPA could replace technetium-99 m galactosyl human serum albumin (GSA) single positron emission computed tomography (SPECT) and indocyanine green (ICG) retention for the measurement of liver functional reserve. METHODS: Twenty eight patients awaiting liver resection for various cancers were included in this retrospective study that was approved by the institutional review board. The Gd-EOB-DTPA MRI sequence acquired five images: unenhanced, double arterial phase, portal phase, and 4 min after injection. Intracellular contrast uptake rate (UR) and extracellular volume (Ve) were calculated from DCE-MRI, along with the ratio of GSA radioactivity of liver to heart-plus-liver and per cent of cumulative uptake from 15-16 min (LHL15 and LU15, respectively) from GSA-scintigraphy. ICG retention at 15 min, Child-Pugh cirrhosis score (CPS) and postoperative Inuyama fibrosis criteria were also recorded. Statistical analysis was with Spearman rank correlation analysis. RESULTS: Comparing MRI parameters with the reference methods, significant correlations were obtained for UR and LHL15, LU15, ICG15 (all 0.4-0.6, P < 0.05); UR and CPS (-0.64, P < 0.001); Ve and Inuyama (0.44, P < 0.05). CONCLUSION: Measures of liver function obtained by routine Gd-EOB-DTPA DCE-MRI with tracer kinetic modelling may provide a suitable method for the evaluation of liver functional reserve. KEY POINTS: • Magnetic resonance imaging (MRI) provides new methods of measuring hepatic functional reserve. • DCE-MRI with Gd-EOB-DTPA offers the possibility of replacing scintigraphy. • The analysis method can be used for preoperative liver function evaluation.