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Background: During systemic therapy, the management of portal hypertension (PH)-related complications is vital. This study aimed to clarify factors associated with the incidence and exacerbation of PH-related complications, including the usefulness of contrast-enhanced computed tomography (CECT) in the management of PH-related complications during systemic therapy. Methods: A total of 669 patients who received systemic therapy as first-line treatment (443 patients for sorafenib, 131 for lenvatinib, and 90 for atezolizumab/bevacizumab [ATZ/BEV]) were enrolled in this retrospective study. Additionally, the lower esophageal intramural vessel diameters (EIV) on CECT and endoscopic findings in 358 patients were compared. Results: The cutoff values of the EIV diameter on CECT were 3.1 mm for small, 5.1 mm for medium, and 7.6 mm for large varices, demonstrating high concordance with the endoscopic findings. esophageal varices (EV) bleeding predictors include EIV ≥ 3.1 mm and portal vein tumor thrombosis (PVTT). In patients without EV before systemic therapy, factors associated with EV exacerbation after 3 months were EIV ≥ 1.9 mm and ATZ/BEV use. Predictors of hepatic encephalopathy (HE) include the ammonia level or portosystemic shunt diameter ≥ 6.8 mm. The incidence of HE within 2 weeks was significantly higher (18%) in patients with an ammonia level ≥ 73 μmol/L and a portosystemic shunt ≥ 6.8 mm. The exacerbating factors for ascites after 3 months were PVTT and low albumin levels. Conclusions: Careful management is warranted for patients with risk factors for exacerbation of PH-related complications; moreover, the effective use of CECT is clinically important. [ABSTRACT FROM AUTHOR]

The pathogenesis of acute liver failure (ALF) involves cell death. Necroptosis is a newly suggested programmed cell death, and receptor-interacting protein kinase 3 (RIPK3) has been reported as a marker for necroptosis. However, there are few reports on necroptosis in ALF. Therefore, we evaluated the role of cell death markers such as cytokeratin (CK) 18, cleaved CK (cCK) 18, and RIPK3 in ALF, as well as cytokines and hepatocyte growth factor (HGF). Seventy-one hospitalized patients with acute liver injury (38 nonsevere hepatitis [non-SH]/22 severe hepatitis [SH]/11 ALF) were studied. No significant difference was found for cytokines, but a substantial increase in HGF levels was found following the severity of hepatitis. The non-SH group had lower levels of CK18 and cCK18 than the SH/ALF group. RIPK3 was significantly lower in the non-SH/SH group than in the ALF group. HGF, RIPK3, and albumin levels were found to be important predictive variables. The present study suggests that cCK18, CK18, and RIPK3 are associated with the severity of hepatitis. RIPK3 and other markers related cell death may be useful for understanding the pathogenesis of ALF and as a prognostic marker of acute liver injury. [ABSTRACT FROM AUTHOR]

Until the end of the follow-up period at our institution at 9 months after TIPS stent reduction, the patient was treated for hepatic encephalopathy with medical therapy, and he did not undergo TIPS stent closure. One limitation of our method is difficultly in predicting the precise reduction rate of the TIPS diameter after AVP and stent placement, because it is determined by comparing the expansion force of the AVP and the stent implanted in parallel. [Extracted from the article]

The effect of the combination of atezolizumab and bevacizumab (Atez/Bev) for hepatocellular carcinoma (HCC) on pulmonary arterial hypertension (PAH) is unknown. Estimation of PAH by using computed tomography (CT) has recently been proposed. Thus, we aimed to estimate the effect of Atez/Bev on PAH using CT. Altogether, 113 patients who received Atez/Bev for HCC were enrolled. Probable PAH was defined as the diameter of the main pulmonary artery (mPA-D) ≥ 33 mm, whereas suspicious PAH was defined as mPA-D ≥ 29 mm or mPA-D/the diameter of the ascending aorta (aAo-D) ≥ 1.0. Before treatment, probable/suspicious PAH were diagnosed in 7 (6.7%)/22 (21.0%) patients, respectively. mPA-D and mPA-D/aAo-D significantly increased after induction of Atez/Bev. The increment of mPA-D was correlated with the occurrence of post-treatment respiratory/heart failure. In analysis of 55 patients who underwent CT at 3 months after the last dose of Atez/Bev, mPA-D and mPA-D/aAo-D significantly decreased. However, in the group with continuous treatment of other molecular-targeted drugs after Atez/Bev, mPA-D and mPA-D/aAo-D showed no significant change. In conclusion, PAH may not be a rare complication in patients with HCC and should be managed carefully because of the possible negative effect of Atez/Bev on PAH. [ABSTRACT FROM AUTHOR]

De novo genes created in the plant mitochondrial genome have frequently been transferred into the nuclear genome via intergenomic gene transfer events. Therefore, plant mitochondria might be a source of de novo genes in the nuclear genome. However, the functions of de novo genes originating from mitochondria and the evolutionary fate remain unclear. Here, we revealed that an Arabidopsis thaliana specific small coding gene derived from the mitochondrial genome regulates floral transition. We previously identified 49 candidate de novo genes that induce abnormal morphological changes on overexpression. We focused on a candidate gene derived from the mitochondrial genome (sORF2146) that encodes 66 amino acids. Comparative genomic analyses indicated that the mitochondrial sORF2146 emerged in the Brassica lineage as a de novo gene. The nuclear sORF2146 emerged following an intergenomic gene transfer event in the A. thaliana after the divergence between Arabidopsis and Capsella. Although the nuclear and mitochondrial sORF2146 sequences are the same in A. thaliana, only the nuclear sORF2146 is transcribed. The nuclear sORF2146 product is localized in mitochondria, which may be associated with the pseudogenization of the mitochondrial sORF2146. To functionally characterize the nuclear sORF2146, we performed a transcriptomic analysis of transgenic plants overexpressing the nuclear sORF2146. Flowering transition-related genes were highly regulated in the transgenic plants. Subsequent phenotypic analyses demonstrated that the overexpression and knockdown of sORF2146 in transgenic plants resulted in delayed and early flowering, respectively. These findings suggest that a lineage-specific de novo gene derived from mitochondria has an important regulatory effect on floral transition. Key message: A large-scale intergenomic gene transfer event involving the nuclear and mitochondrial genomes in the Arabidopsis thaliana lineage created a small coding gene that regulates floral timing. [ABSTRACT FROM AUTHOR]

The screening of gastroesophageal varices (GEV) is critical in hepatocellular carcinoma (HCC) management. Contrast-enhanced computed tomography (CECT) is often performed in patients with HCC. Therefore, this study aimed to examine the use of CECT in screening for GEV and predicting GEV bleeding. This retrospective study enrolled 312 consecutive patients who are initially diagnosed with HCC, measured the lower esophageal (EIV) and fundal intramural vessel (FIV) diameter on CECT, examined the changes after 1, 2, and 3 years, and verified the relationship with GEV bleeding. The EIV and FIV diameter on CECT correlates well with endoscopic variceal classification. EIV significantly worsened after 2 and 3 years. FIV showed worsening at both 1, 2, and 3 years. Cumulative GEV bleeding rates were 3.7% at 1 year and 6.2% at 3 years. The multivariate analysis revealed that EIV, FIV, and portal vein tumor thrombus were associated with GEV bleeding. Furthermore, EIV deterioration at 1, 2, and 3 years correlated with GEV bleeding. In conclusion, CECT is useful in variceal management during the longitudinal clinical course of HCC, and has the potential to decrease screening endoscopy. With deterioration in EIV, treatments should be considered due to a high-risk GEV bleeding. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Its early phase is characterized by a relapse-remitting disease course, followed by disability progression in the later stage. While chronic inflammation accompanied with degeneration is well-established as the key pathological feature, the pathogenesis of MS, particularly progressive MS, remains elusive. Sulfatide is a major glycolipid component of myelin, and previous studies in experimental autoimmune encephalomyelitis mouse models have demonstrated it to have immune-protective functions. Notably, sulfatide concentration is increased in the serum and cerebrospinal fluid of patients with MS, particularly those in a progressive disease course. Here, we show that the myelin-glycolipid sulfatide displays an ability to suppress the proliferation of polyclonally activated human T cells. Importantly, this suppressive effect was impaired in T cells obtained from MS patients having higher disability status. Therefore, it is plausible that progression of MS is associated with an escape from the immune-regulatory effect of sulfatide. Our study suggests that, although the precise mechanisms remain unrevealed, an escape of T cells from immunosuppression by sulfatide is associated with disease progression in the advanced stage. Further studies will provide novel insights into the pathogenesis of MS, particularly regarding disease progression, and help develop novel treatment strategies for this challenging disease. [ABSTRACT FROM AUTHOR]

Background: With the evolution of personalized medicine in the field of oncology, which includes optimal treatment selection using next-generation sequencing-based companion diagnostic systems and tumor-agnostic treatments according to common biomarkers, a liver tumor biopsy technique that can obtain a sufficient specimen volume must be established. The current study aimed to evaluate the safety and availability of a liver tumor biopsy technique with multiple puncture sites made using a coaxial introducer needle and embolization with gelatin sponge particles. Methods: Patients with primary or metastatic liver cancer who underwent liver tumor biopsies with puncture tract embolization using gelatin sponge (Spongel®) from October 2019 to September 2020 were included in the study. The complication and diagnostic rates were evaluated, and whether the specimen volume was sufficient for Foundation® CDx was investigated. Results: In total, 96 patients were enrolled in this analysis. The median total number of puncture times per patient was 3 (range 1–8). The pathological diagnostic rate was 79.2%. Using the FoundationOne® CDx, specimens with a sufficient volume required for genomic medicine were collected in 84.9% of patients. The incidence rate of bleeding was 4.2% (n = 4), and only one patient presented with major bleeding requiring transfusion. Conclusions: Liver biopsy with puncture tract embolization using a gelatin sponge may be safe and effective for collecting specimens with a volume sufficient for modern cancer treatments. [ABSTRACT FROM AUTHOR]

Background: It has been reported that in conventional open surgery, approximately 10% of surgical gloves are perforated during surgery without being noticed. To protect both the patient and medical staff from harm, double gloving or changing gloves routinely at certain intervals during surgery is recommended. However, whether these protective measures are also necessary for laparoscopic colorectal surgery is unknown because the actual perforation rate during laparoscopic procedures is unclear. Methods: Seventy-seven laparoscopic colorectal surgeries were evaluated, and a total of 616 surgical gloves used in the surgeries were collected for analysis. The presence of glove perforation was tested by the standard water-leak test method (EN455-1). Results: Seven perforations were detected (1.1%). The duration of the laparoscopic procedure was not a statistically significant risk factor for glove perforation (p = 0.41). Postoperative surgical site infections (SSIs) were observed in 12 cases (15.6%), but there was no significant correlation between the presence of glove perforation and SSI (p = 0.92). According to the bacterial cultivation results, the majority of causative agents of SSI were enterobacteria, which belong to the major gut flora. Conclusion: Although the perforation rate was considerably lower than that in open surgery, surgical glove perforation occurred during laparoscopic procedures. Double gloving in laparoscopic colorectal surgery is recommended not to prevent SSI but to protect medical workers from harmful infections after direct contact with the patient. [ABSTRACT FROM AUTHOR]

Microbial flora is investigated to be related with neuropathological conditions in Alzheimer's disease (AD), and is attracting attention as a drug discovery resource. However, the relevance between the soil microbiota and the pathological condition has not been fully clarified due to the difficulty in isolation culture and the component complexity. In this study, we established a library of secondly metabolites produced in microorganism to investigate the potential effect of microorganisms on the production of amyloid β (Aβ), one of the most representative pathogens of AD. We conducted a library screening to quantify Aβ and neuronal toxicity by using cortical neurons from human induced pluripotent stem cells (iPSCs) of AD patients after adding secondary metabolites. Screening results and following assessment of dose-dependency identified Verrucarin A, produced in Myrothecium spp., showed 80% decrease in Aβ production. Furthermore, addition of Mer-A2026A, produced in Streptomyces pactum, showed increase in Aβ42/40 ratio at the low concentration, and decrease in Aβ production at the higher concentration. As a result, established library and iPSC-based phenotyping assay clarified a direct link between Aβ production and soil microorganisms. These results suggest that Aβ-microorganism interaction may provide insight into the AD pathophysiology with potential therapeutics. [ABSTRACT FROM AUTHOR]

Organoid technology provides an opportunity to generate brain-like structures by recapitulating developmental steps in the manner of self-organization. Here we examined the vertical-mixing effect on brain organoid structures using bioreactors and established inverted brain organoids. The organoids generated by vertical mixing showed neurons that migrated from the outer periphery to the inner core of organoids, in contrast to orbital mixing. Computational analysis of flow dynamics clarified that, by comparison with orbital mixing, vertical mixing maintained the high turbulent energy around organoids, and continuously kept inter-organoid distances by dispersing and adding uniform rheological force on organoids. To uncover the mechanisms of the inverted structure, we investigated the direction of primary cilia, a cellular mechanosensor. Primary cilia of neural progenitors by vertical mixing were aligned in a multidirectional manner, and those by orbital mixing in a bidirectional manner. Single-cell RNA sequencing revealed that neurons of inverted brain organoids presented a GABAergic character of the ventral forebrain. These results suggest that controlling fluid dynamics by biomechanical engineering can direct stem cell differentiation of brain organoids, and that inverted brain organoids will be applicable for studying human brain development and disorders in the future. Dang Ngoc Anh Suong et al find that vertical mixing generates iPSC-derived brain organoids displaying an inverted structure with neurons localising at the centre and neural progenitors at the outside. This study illustrates the influence of fluid mechanics relevant to the direction of primary cilia on stem cell differentiation. [ABSTRACT FROM AUTHOR]

FGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19high (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19low (n = 105) patients, there were no significant differences between FGF19high (n = 21) and FGF19low (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib. [ABSTRACT FROM AUTHOR]

Increase in atmospheric carbon dioxide (CO2) has a significant effect on plant growth and development. To explore the elevated-CO2 response, we generated transcriptional profiles over a time course (2 h–14 days) of exposure to elevated CO2 in Arabidopsis thaliana. Genes related to photosynthesis were down-regulated and circadian rhythm-related genes were abnormally regulated in the early to middle phase of elevated CO2 exposure. To understand the novel mechanism of elevated CO2 signaling, we focused on 42 unknown small coding genes that showed differential expression patterns under elevated CO2 conditions. Four transgenic plants overexpressing the small coding gene exhibited a growth-defective phenotype under elevated CO2 but not under current CO2. Transcriptome analysis showed that circadian rhythm-related genes were commonly regulated in four transgenic plants. These circadian rhythm-related genes were transcribed in the dark when CO2 concentrations in the leaf was high. Taken together, our identified four small coding genes are likely to participate in elevated CO2 signaling to the circadian rhythm. Key Message: Transcriptome analysis was performed under elevated CO2 condition in Arabidopsis thaliana. We identified small coding genes associated with signal molecules from elevated CO2 to circadian rhythm genes. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is occasionally associated with autoimmune diseases in the central nervous system (CNS), such as neuromyelitis optica spectrum disorder (NMOSD), multiple sclerosis (MS), Morvan syndrome, and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Here, we report five original cases associated with autoimmune disorders in the CNS among 42 patients with MG in a single tertiary hospital in Japan (11.9%). In four of these five cases, the second disease developed when the preceding disease was unstable. Accurate diagnosis of the newly developing disease may be difficult in such cases, because some neurological symptoms can be seen in both disorders. This implies the great importance of recognizing the possible co-occurrence of MG and disorders in the CNS. In addition, a comprehensive review of the literature revealed distinct clinical characteristics depending on the associated disease in the CNS, including thymic pathology and temporal relationship between MG and associated CNS disorders. Notably, NMOSD usually develops after the onset of MG and thymectomy, in clear contrast to MS. Thymoma is highly prevalent among patients with Morvan syndrome, in contract to cases with NMOSD and MS. The analysis of clinical characteristics, representing the first such investigation to the best of our knowledge, suggests different pathogeneses of these autoimmune diseases in the CNS, and provides significant implications for clinical practice. [ABSTRACT FROM AUTHOR]

Background: To examine the hemodynamic effect of the left gastric artery (LGA) on the esophageal varices (EV) in cirrhosis.Methods: This was a prospective study performed in 48 cirrhosis patients (35 men, 13 women; median age 61.6 ± 11.3 years, range 38-83 years) with EV (medium 35, large 13), who underwent selective LGA angiography, hepatic venous catheterization, endoscopic ultrasonography (EUS) and Doppler ultrasonography before endoscopic treatment for EV. Angiographic findings including diameter of the main trunk, detection time of EV, and mild/severe degree of peripheral staining were assessed. The median period of post-treatment observation was 17.1 months.Results: LGA angiograms were successfully obtained in 45/48 patients. EV were demonstrated in 45/45 patients, with a mean detection time of 6.9 s (2-21), which was longer in patients with variceal recurrence (7.0 s) than in those without (5.6 s, P = 0.480). The staining was mild in 25 patients (55.6 %) and severe in 20 patients (44.4 %), and portal hypertensive gastropathy was more frequent in the latter (13/20, 65.0 %) than in the former (7/25, 28.0 %, P = 0.013). Multivariate analysis showed that pre-treatment detection time (P = 0.04) and post-treatment submucosal vascular area at the cardia wall by EUS (P = 0.036) were significant factors for variceal recurrence. No other factors, including hepatic venous pressure gradient and Doppler parameters, showed significant relationships with the variceal recurrence.Conclusions: The hemodynamics in the LGA may act as an initiator of variceal formation, showing close linkage with variceal recurrence, and independent of portal pressure. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to clarify the influence of hepatic fibrosis on metachronous liver-specific recurrence in colorectal cancer (CRC) patients who underwent colorectal surgery with curative intent. Non-alcoholic steatohepatitis (NASH) is closely associated with hepatic fibrosis (HF). The number of patients who suffer from NASH is increasing because of the consumption of high-calorie diets. It remains unclear how much of an impact NASH and HF have on the development of liver metastasis in CRC.Methods: Patients who underwent curative surgical resection for CRC between 2000 and 2011 were included in this study. We evaluated the progression of HF by the non-alcoholic fatty liver disease fibrosis score (NFS) based on preoperative blood test results, age, body mass index, and diabetes mellitus. Patients were grouped according to high (fibrotic liver; FL) or low (normal liver; NL) NFS. The influence of HF on hepatic recurrence was assessed by survival analyses.Results: A total of 953 CRC patients were enrolled, comprising 293 in stage I, 327 in stage II, and 333 in stage III. The patients included were categorised as FL (77) or NL (876). The hepatic recurrence rates were 5.3% in the NL group and 10.4% in the FL group (P=0.02), whereas the overall recurrence rates were 16.0% in the NL group and 20.7% in the FL group (P=0.03). The 5-year liver-specific recurrence-free survival rate in the FL group was significantly poorer than that in the NL group (FL 89.1%, 95% confidence interval (CI) 78.4-94.7 vs NL 96.0%, 95% CI 94.3-97.2, log-rank test P<0.01). Multivariate analysis demonstrated that HF significantly promoted liver-specific recurrence compared with NL (HR=2.98, 95% CI 1.23-7.21; P=0.02).Conclusion: HF is a valuable prognostic factor for hepatic recurrence after curative surgical resection of CRC. [ABSTRACT FROM AUTHOR]

Purpose: Anastomotic leakage (AL) is a critical complication of colorectal cancer surgery. The transanal drainage tube (TDT) is designed to prevent AL caused by decompression and stasis at the anastomosis. We conducted this study to investigate the feasibility of using the TDT to prevent AL following double-stapling technique reconstruction (DST). Methods: The subjects of this study were 179 patients who underwent curative resection and DST reconstruction for sigmoid colon and rectal cancer in our institution between 2008 and 2013. We analyzed the effectiveness of the TDT for preventing AL. Results: A TDT was placed in 78 patients (43.6 %, TDT group) and not placed in the remaining 101 patients (56.4 %, NTDT group). AL developed in 2 (2.6 %) patients from the TDT group and in 14 (13.9 %) patients from the NTDT group ( p = 0.009). Univariate analysis revealed that AL was significantly correlated with tumor distance from the anal verge (AV), the number of staples, and TDT placement. Multivariate analysis revealed a significantly positive correlation between AL and AV [OR 0.877 (0.783-0.982) p = 0.023] and a significantly negative correlation between AL and TDT placement [OR 0.07 (0.013-0.374) p = 0.002]. Conclusions: Anastomotic decompression with TDT placement may prevent AL after colorectal cancer surgery with DST reconstruction. [ABSTRACT FROM AUTHOR]

Objective: The objective was to examine the effect of splenic circulation using a microbubble agent to assess the severity of portal hypertension. Methods: This prospective study consisted of 91 subjects (63.0 ± 12.6 years, 30-86; 60 males, 31 females), 62 cirrhosis and 29 controls, who underwent both Doppler ultrasound and contrast-enhanced ultrasound with a perflubutane microbubble agent. Two microbubble-based parameters for splenic circulation, the minimum circulation time (MCT, s) and the peak enhancement time (PET, s), were assessed with respect to the hepatic venous pressure gradient (HVPG) and other clinical findings. Results: The MCT and PET showed significant differences between cirrhosis (5.7 ± 1.8; 14.6 ± 3.0) and controls (4.0 ± 1.9, p < 0.0001; 8.9 ± 2.3, p < 0.0001), respectively. However, only PET offered positive correlations with wedged hepatic venous pressure ( r = 0.4648, p = 0.0001) and HVPG ( r = 0.4573, p = 0.0001). The area under the receiver operating characteristics curve to identify HVPG ≥ 10 mmHg, and 12 mmHg was 0.76 and 0.76, respectively. Conclusions: The microbubble-based non-invasive assessment of the splenic circulation is effective to identify the severity of portal hypretension presumably by reflecting congestion of splenic venous flow due to increased portal venous pressure. Key Points: • There is a potential link between splenic circulation and portal hypertension. • Microbubble-based assessment of splenic circulation is predictive of the severity of portal hypertension. • Interobserver variability was sufficient in the assessment of splenic enhancement sonograms. [ABSTRACT FROM AUTHOR]

Congenital hepatic fibrosis (CHF) is a form of autosomal recessive polycystic kidney disease. Because of the common underlying pathophysiology of ductal plate malformation, CHF can be accompanied by an abnormal biliary appearance, which is characterized by a saccular or fusiform dilatation of the bile ducts. We encountered the case of a 35-year-old man suffering from CHF concomitant with esophageal varices, which were treated by endoscopic sclerotherapy. The patient had elevated serum concentrations of alkaline phosphatase and γ-glutamyl transpeptidase without apparent biliary disease, including hepatolithiasis or a history of cholangitis. Magnetic resonance cholangiography showed an abnormal biliary appearance, which was not saccular or fusiform but had multiple stenosis with unknown causes. B-mode sonogram showed multiple comet tail artifacts in the liver parenchyma, probably corresponding to the compact fibrosis bands and bile in the bile duct as well as peripheral bile duct dilatation, which was proven pathologically. We propose that multiple comet tail artifacts in the liver may suggest the presence of a bile duct abnormality in patients with CHF, suggesting the potential risk for developing biliary complications. [ABSTRACT FROM AUTHOR]

Purpose: Little is known about portal vein thrombosis (PVT) after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). We aimed to determine the incidence, background, and natural history of RFA-related PVT. Methods: This is a retrospective study of 317 patients (219 males and 98 females) with HCC treated by RFA. Clinical data were compared between patients with and without PVT detected by ultrasound/CT. The median follow-up period after RFA was 15.8 months. Results: PVT was detected in 6 (1.9 %) of 317 patients, 6 (0.8 %) of 802 treatments for HCC, and 6 (0.6 %) of 964 sessions of RFA. Body mass index was significantly higher in patients with PVT (26.9 ± 3.1 kg/m 2) than in those without (22.9 ± 3.5 kg/m 2, p = 0.0075). PVT was significantly more frequent in RFA for the left lobe of the liver (2.7 %) than for the other sites (0 %, p < 0.0001). Five of the six patients received no treatment for PVT, with natural outcomes of disappearance in one patient, improvement in one patient, and unchanged appearance in three patients. Anticoagulation was applied in the one remaining patient and resulted in a successful recanalization. In the six patients, there was no significant difference in hepatic functional reserve between baseline and time of detection of PVT. Conclusions: These results indicated that a high body mass index and RFA for HCC in the left lobe might be significant risk factors for PVT and that RFA-related PVT was rarely progressive with little influence on liver function. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica (NMO) and associated NMO spectrum disorders (NMOSDs) are neuroinflammatory diseases that frequently result in severe neurological disabilities. The aim of this study was to explore additional treatment options for NMO/NMOSD patients who are seropositive for anti-aquaporin 4 (AQP4) antibodies. We retrospectively evaluated the efficacy of immunosuppressants for NMO/NMOSDs by reviewing the clinical records of 52 patients confirmed as seropositive for anti-AQP4 antibodies. Of the 52 patients, 26 (23 women, three men) had received at least one kind of immunosuppressant other than corticosteroids. After eliminating ineligible cases, we evaluated the following 24 treatments in 22 patients (20 women, two men) that used azathioprine (AZA) ( n = 9), cyclophosphamide ( n = 1), cyclosporine A (CyA) ( n = 9), tacrolimus ( n = 2), methotrexate ( n = 1), and mizoribine ( n = 2). Both AZA and CyA treatments allowed us to decrease the median dose of the coadministered prednisone without affecting the expanded disability severity scale scores. In patients with relapsing-remitting courses, the annual relapse rate decreased from 1.7 (1.2-2.7) to 0.47 (0.36-0.59) after AZA treatments ( n = 6, P = 0.028), and also showed a significant decrease from 2.7 (1.8-4.3) to 0.38 (0-0.97) after CyA treatment ( n = 8, P = 0.012). These results indicate that CyA as well as AZA may help stabilize the disease activity in NMO/NMOSD patients seropositive for anti-AQP4 antibodies. This is the first case series study demonstrating the efficacy of CyA for the treatment of NMO/NMOSDs. [ABSTRACT FROM AUTHOR]

The effect of pulsed DC current on the atomic diffusion of an Nb–C system using Spark Plasma Sintering (SPS) was investigated. In all experiments, a current density of approximately 723 A/cm2 was applied to the specimen and used in a temperature range of 1,673–1,973 K. From the results of X-ray diffraction analysis, the product phases formed between Nb and C were found to be Nb2C and NbC. The growth of product layers significantly increased in the presence of current. However, the thickness of the product layer did not change in the current direction in the SPS. The activation energies for the formation of the Nb2C and NbC layers were calculated to be 298 ± 4 kJ/mol and 282 ± 3 kJ/mol in the presence of current, which were similar values compared to the activation energies of 300 ± 5 kJ/mol and 285 ± 2 kJ/mol in the absence of current, respectively. [ABSTRACT FROM AUTHOR]

Interactions with self?major histocompatibility complex molecules on dendritic cells (DCs) are important for the survival of mature CD4+ T cells. We have followed the DC-mediated signal from the T cell surface to the nucleus and identified a pattern of activation that correlates with increased in vitro survival. This response is induced exclusively by DCs and is likely associated with a modulation of the T cell activation threshold. We have also found that DC-mediated activation results in antigen-independent cytokine gene expression, which points to a new role for DCs in shaping the cytokine milieu. Such antigen-independent activation of T cells may play a role in protective immunity, but may also induce and perpetuate autoimmune states such as multiple sclerosis. [ABSTRACT FROM AUTHOR]

Myelin-specific T lymphocytes are considered essential in the pathogenesis of multiple sclerosis. The myelin basic protein peptide (a.a. 83-99) represents one candidate antigen; therefore, it was chosen to design an altered peptide ligand, CGP77116, for specific immunotherapy of multiple sclerosis. A magnetic resonance imaging-controlled phase II clinical trial with this altered peptide ligand documented that it was poorly tolerated at the dose tested, and the trial had therefore to be halted. Improvement or worsening of clinical or magnetic resonance imaging parameters could not be demonstrated in this small group of individuals because of the short treatment duration. Three patients developed exacerbations of multiple sclerosis, and in two this could be linked to altered peptide ligand treatment by immunological studies demonstrating the encephalitogenic potential of the myelin basic protein peptide (a.a. 83-99) in a subgroup of patients. These data raise important considerations for the use of specific immunotherapies in general. [ABSTRACT FROM AUTHOR]

Elucidating the cellular immune response to infectious agents is a prerequisite for understanding disease pathogenesis and designing effective vaccines. In the identification of microbial T-cell epitopes, the availability of purified or recombinant bacterial proteins has been a chief limiting factor. In chronic infectious diseases such as Lyme disease, immune-mediated damage may add to the effects of direct infection by means of molecular mimicry to tissue autoantigens. Here, we describe a new method to effectively identify both microbial epitopes and candidate autoantigens. The approach combines data acquisition by positional scanning peptide combinatorial libraries and biometric data analysis by generation of scoring matrices. In a patient with chronic neuroborreliosis, we show that this strategy leads to the identification of potentially relevant T-cell targets derived from both Borrelia burgdorferi and the host. We also found that the antigen specificity of a single T-cell clone can be degenerate and yet the clone can preferentially recognize different peptides derived from the same organism, thus demonstrating that flexibility in T-cell recognition does not preclude specificity. This approach has potential applications in the identification of ligands in infectious diseases, tumors and autoimmune diseases. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about an HLA-B54 case of recurrent encephalitis.