Histological differentiation between sporadic and colitis-associated intestinal cancer in a nationwide study: A propensity-score-matched analysis.

BACKGROUND AND AIM: Colitis-associated intestinal cancer (CAC) can develop in patients with inflammatory bowel disease; however, the malignant grade of CAC may differ from that of sporadic colorectal cancer (CRC). Therefore, we compared histological findings distinct from cancer stage between CAC and sporadic CRC to evaluate the features of CAC. METHODS: We reviewed the clinical and histological data collected from a nationwide database in Japan between 1983 and 2020. Patient characteristics were compared to distinguish ulcerative colitis (UC), Crohn's disease (CD), and sporadic CRC. Comparisons were performed by using all collected data and propensity score-matched data. RESULTS: A total of 1077 patients with UC-CAC, 297 with CD-CAC, and 136 927 with sporadic CRC were included. Although the prevalence of well or moderately differentiated adenocarcinoma (Tub1 and Tub2) decreased according to tumor progression for all diseases (P < 0.01), the prevalence of other histological findings, including signet ring cell carcinoma, mucinous carcinoma, poorly differentiated adenocarcinoma, or squamous cell carcinoma, was significantly higher in CAC than in sporadic CRC. Based on propensity score-matched data for 982 patients with UC and 268 with CD, the prevalence of histological findings other than Tub1 and Tub2 was also significantly higher in those with CAC. At pT4, mucinous carcinoma occurred at a significantly higher rate in patients with CD (45/86 [52.3%]) than in those with sporadic CRC (13/88 [14.8%]) (P < 0.01). CONCLUSION: CAC, including early-stage CAC, has a higher malignant grade than sporadic CRC, and this difference increases in significance with tumor progression.

Novel insights into presenilin 1 mutation associated with a distinctive dementia phenotype and cotton wool plaques.

BACKGROUND: The mutations in the presenilin 1 gene (PSEN1) are the main cause of familial Alzheimer's disease. PSEN1 mutations affect amyloid-beta peptide production, which accumulates in the brain as senile plaque and cotton wool plaques (CWPs) and relates to other neurodegenerative disorders. Here we report the second case of the PSEN1 G266S mutation, which showed distinctive neuropathological features, including abundant CWPs. Lewy body pathology, and altered amyloid-beta production. METHOD: Using the proband's samples, we performed genetic analysis of the PSEN1, APP, MAPT, and APOE genes, histopathological and immunohistochemical analysis of the brain tissue, and biochemical analysis of Aß production in COS cells transfected with wild-type or mutant PSEN1. RESULTS: The patient presented with memory loss, abnormal behavior, and visual hallucinations. Brain scans showed reduced blood flow, mild atrophy, and white matter lesions. Genetic analysis revealed a heterozygous mutation at codon 266 (G266S) of PSEN1 and polymorphism of MAPT (Q230R). The brain had many CWPs, severe cerebral amyloid angiopathy (CAA), senile plaque, Lewy bodies, and neurites. Electron microscopy displayed myelinated fiber degeneration, mitochondrial damage, and amyloid fibrils in the white matter. The production level of Aß42 in PSEN1 G266S-transfected cells significantly increased. CONCLUSION: Our findings suggest that the PSEN1 G266S mutation may cause a heterogeneous clinical and pathological phenotype, influenced by other genetic or environmental factors.

Validation of the area under the Watts factor curve during the voiding cycle as a novel parameter for diagnosing detrusor underactivity in females.

OBJECTIVE: Detrusor underactivity (DU) is a common cause of lower urinary tract symptoms (LUTS). To date, no consensus has been reached on the urodynamic criteria for defining DU. We previously proposed the area under the curve of the Watts factor (WF-AUC) as a new parameter for diagnosing DU. By comparing previously reported five criteria for DU and WF-AUC, we analyzed whether the WF-AUC could assess detrusor contraction in women with LUTS. METHODS: Using urodynamic data of consecutive 77 women with LUTS, first, we classified DU based on previously reported five criteria. Second, we assessed the potential correlation between multiple parameters and WF-AUC. Third, receiver operating characteristic curve analysis was performed to determine the cutoff value of WF-AUC for diagnosing DU based on previously reported five criteria. Fourth, a linear regression analysis was conducted and compared using multiple criteria and female bladder outlet obstruction index (BOOIf). RESULTS: WF-AUC was positively correlated with the maximum values of WF, bladder contractility index (BCI), and projected isovolumetric pressure 1 (PIP1) with correlation coefficients of 0.63, 0.57, and 0.34, respectively. AUC for diagnosing DU based on previously reported five criteria ranging from 0.773 to 0.896 with different cutoff values of AUC-WF. The Spearman's correlation test revealed that BOOIf was significantly correlated with BCI, but not Wmax, PIP1 and WF-AUC. CONCLUSIONS: This study demonstrated the non-inferiority of the WF-AUC compared to previously reported criteria for defining DU. Depending on the cutoff value, the WF-AUC could appropriately evaluate women with DU, regardless of the presence of BOO.

Impact of Portable Normothermic Machine Perfusion for Liver Transplantation From Adult Deceased Donors.

OBJECTIVE: To assess how liver allografts preserved using portable normothermic machine perfusion (NMP) compare against those that underwent ischemic cold storage (ICS) in the setting of donation after brain death (DBD) and donation after circulatory death (DCD) liver transplantation (LT). BACKGROUND: Compared with conventional ICS, NMP may offer more homeostatic preservation, permit physiological assessment of organ function, and provide opportunities for graft improvement/modification. We report a single-center US experience of liver NMP. METHODS: A single-center, retrospective analysis of collected data on 541 adult whole LTs from 469 DBD donors [NMP (n = 58) vs ICS (n = 411)] and 72 DCD donors [NMP (n = 52) vs ICS (n = 20)] between January 2016 and December 2022. RESULTS: In DBD LT, male sex [odds ratio (95% CI): 1.83 (1.08-3.09)] and >10% macrosteatosis of the donor liver [1.85 (1.10-3.10)] were statistically significant independent risk factors of early allograft dysfunction (EAD). Donor age >40 years and cold ischemia time >7 hours were independent risk factors of reperfusion syndrome (RPS). One-year, 3-year, and 5-year incidences of ischemic cholangiopathy (IC) did not differ significantly in DBD cases between the NMP and ICS cohorts. In DCD LT, NMP was an independent protective factor against EAD [0.11 (0.03-0.46)] and RPS [0.04 (0.01-0.25)]. The incidence of IC in the DCD cases at 1-year and 3-year time points was significantly lower in the NMP cohort (1.9% compared with 20% in the ICS group). CONCLUSIONS: Compared with conventional ICS, NMP can significantly reduce the incidence of EAD, RPS, and IC after DCD LT.

CORE-IBD: A Multidisciplinary International Consensus Initiative to Develop a Core Outcome Set for Randomized Controlled Trials in Inflammatory Bowel Disease.

BACKGROUND & AIMS: End points to determine the efficacy and safety of medical therapies for Crohn's disease (CD) and ulcerative colitis (UC) are evolving. Given the heterogeneity in current outcome measures, harmonizing end points in a core outcome set for randomized controlled trials is a priority for drug development in inflammatory bowel disease. METHODS: Candidate outcome domains and outcome measures were generated from systematic literature reviews and patient engagement surveys and interviews. An iterative Delphi process was conducted to establish consensus: panelists anonymously voted on items using a 9-point Likert scale, and feedback was incorporated between rounds to refine statements. Consensus meetings were held to ratify the outcome domains and core outcome measures. Stakeholders were recruited internationally, and included gastroenterologists, colorectal surgeons, methodologists, and clinical trialists. RESULTS: A total of 235 patients and 53 experts participated. Patient-reported outcomes, quality of life, endoscopy, biomarkers, and safety were considered core domains; histopathology was an additional domain for UC. In CD, there was consensus to use the 2-item patient-reported outcome (ie, abdominal pain and stool frequency), Crohn's Disease Activity Index, Simple Endoscopic Score for Crohn's Disease, C-reactive protein, fecal calprotectin, and co-primary end points of symptomatic remission and endoscopic response. In UC, there was consensus to use the 9-point Mayo Clinic Score, fecal urgency, Robarts Histopathology Index or Geboes Score, fecal calprotectin, and a composite primary end point including both symptomatic and endoscopic remission. Safety outcomes should be reported using the Medical Dictionary for Regulatory Activities. CONCLUSIONS: This multidisciplinary collaboration involving patients and clinical experts has produced the first core outcome set that can be applied to randomized controlled trials of CD and UC.

Crohn's Disease-Associated Anorectal Cancer Has a Poor Prognosis With High Local Recurrence: A Subanalysis of the Nationwide Japanese Study.

INTRODUCTION: Colorectal cancer (CRC) is one of the major life-threatening complications in patients with Crohn's disease (CD). Previous studies of CD-associated CRC (CD-CRC) have involved only small numbers of patients, and no large series have been reported from Asia. The aim of this study was to clarify the prognosis and clinicopathological features of CD-CRC compared with sporadic CRC. METHODS: A large nationwide database was used to identify patients with CD-CRC (n = 233) and sporadic CRC (n = 129,783) over a 40-year period, from 1980 to 2020. Five-year overall survival (OS), recurrence-free survival (RFS), and clinicopathological characteristics were investigated. The prognosis of CD-CRC was further evaluated in groups divided by colon cancer and anorectal cancer (RC). Multivariable Cox regression analysis was used to adjust for confounding by unbalanced covariables. RESULTS: Compared with sporadic cases, patients with CD-CRC were younger; more often had RC, multiple lesions, and mucinous adenocarcinoma; and had lower R0 resection rates. Five-year OS was worse for CD-CRC than for sporadic CRC (53.99% vs 71.17%, P < 0.001). Multivariable Cox regression analysis revealed that CD was associated with significantly poorer survival (hazard ratio 2.36, 95% confidence interval: 1.54-3.62, P < 0.0001). Evaluation by tumor location showed significantly worse 5-year OS and RFS of CD-RC compared with sporadic RC. Recurrence was identified in 39.57% of CD-RC cases and was mostly local. DISCUSSION: Poor prognosis of CD-CRC is attributable primarily to RC and high local recurrence. Local control is indispensable to improving prognosis.

Effect of Biologics on the Risk of Advanced-Stage Inflammatory Bowel Disease-Associated Intestinal Cancer: A Nationwide Study.

INTRODUCTION: The aim of this study was to evaluate the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer from a nationwide multicenter data set. METHODS: The medical records of patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020 were included in this study. Therapeutic agents were classified into 3 types: biologics, 5-aminosalicylic acid, and immunomodulators. The pathological cancer stage was compared based on the drug used in both patients with CD and UC. RESULTS: In total, 1,042 patients (214 CD and 828 UC patients) were included. None of the drugs were significantly associated with cancer stage in the patients with CD. In the patients with UC, an advanced cancer stage was significantly associated with less use of biologics (early stage: 7.7% vs advanced stage: 2.0%, P < 0.001), 5-aminosalicylic acid, and immunomodulators. Biologic use was associated with a lower incidence of advanced-stage cancer in patients diagnosed by regular surveillance (biologics [-] 24.5% vs [+] 9.1%, P = 0.043), but this was not the case for the other drugs. Multivariate analysis showed that biologic use was significantly associated with a lower risk of advanced-stage disease (odds ratio = 0.111 [95% confidence interval, 0.034-0.356], P < 0.001). DISCUSSION: Biologic use was associated with a lower risk of advanced IBD-associated cancer in patients with UC but not with CD. The mechanism of cancer progression between UC and CD may be different and needs to be further investigated.

Location-weighted versus Volume-weighted Mismatch at MRI for Response to Mechanical Thrombectomy in Acute Stroke.

Background A target mismatch profile can identify good clinical response to recanalization after acute ischemic stroke, but does not consider region specificities. Purpose To test whether location-weighted infarction core and mismatch, determined from diffusion and perfusion MRI performed in patients with acute stroke, could improve prediction of good clinical response to mechanical thrombectomy compared with a target mismatch profile. Materials and Methods In this secondary analysis, two prospectively collected independent stroke data sets (2012-2015 and 2017-2019) were analyzed. From the brain before stroke (BBS) study data (data set 1), an eloquent map was computed through voxel-wise associations between the infarction core (based on diffusion MRI on days 1-3 following stroke) and National Institutes of Health Stroke Scale (NIHSS) score. The French acute multimodal imaging to select patients for mechanical thrombectomy (FRAME) data (data set 2) consisted of large vessel occlusion-related acute ischemic stroke successfully recanalized. From acute MRI studies (performed on arrival, prior to thrombectomy) in data set 2, target mismatch and eloquent (vs noneloquent) infarction core and mismatch were computed from the intersection of diffusion- and perfusion-detected lesions with the coregistered eloquent map. Associations of these imaging metrics with early neurologic improvement were tested in multivariable regression models, and areas under the receiver operating characteristic curve (AUCs) were compared. Results Data sets 1 and 2 included 321 (median age, 69 years [IQR, 58-80 years]; 207 men) and 173 (median age, 74 years [IQR, 65-82 years]; 90 women) patients, respectively. Eloquent mismatch was positively and independently associated with good clinical response (odds ratio [OR], 1.14; 95% CI: 1.02, 1.27; P = .02) and eloquent infarction core was negatively associated with good response (OR, 0.85; 95% CI: 0.77, 0.95; P = .004), while noneloquent mismatch was not associated with good response (OR, 1.03; 95% CI: 0.98, 1.07; P = .20). Moreover, adding eloquent metrics improved the prediction accuracy (AUC, 0.73; 95% CI: 0.65, 0.81) compared with clinical variables alone (AUC, 0.65; 95% CI: 0.56, 0.73; P = .01) or a target mismatch profile (AUC, 0.67; 95% CI: 0.59, 0.76; P = .03). Conclusion Location-weighted infarction core and mismatch on diffusion and perfusion MRI scans improved the identification of patients with acute stroke who would benefit from mechanical thrombectomy compared with the volume-based target mismatch profile. Clinical trial registration no. NCT03045146 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Nael in this issue.

Nutrition and diet in inflammatory bowel disease.

PURPOSE OF REVIEW: This study was to review the current evidence for dietary risk factors for developing inflammatory bowel disease (IBD), and therapeutic benefit of dietary and enteral interventions in IBD. RECENT FINDINGS: A Westernized diet rich in protein, fats and refined carbohydrates and low in fibre, fruits and vegetables may increase risk of developing IBD. Nevertheless, there are methodological limitations in case-control studies, which can affect the accuracy of the outcomes. Currently, various dietary interventions and supplements have been attempted to control the disease activity of IBD, but none of them showed striking efficacy. Exclusive enteral nutrition (EEN) is recommended as the first-line therapy in paediatric patients with active Crohn's disease. EEN is recommended in adults with good adherence to enteral formula and with intolerance to corticosteroids. Partial enteral nutrition is not recommended as primary therapy for the maintenance of remission, but it is used when undernutrition cannot be treated sufficiently with diets. SUMMARY: Dietary risk factors for IBD, and the efficacies of dietary and enteral interventions need to be confirmed by large, well designed studies.

Enzymatically modified isoquercitrin in soy protein temporarily enhanced the plasma amino-acid concentrations, antioxidant index, and plasma hormone levels: a randomized, double-blind cross-over trial.

This study investigated the effects of a dietary protein supplement containing enzymatically modified isoquercitrin (EMIQ) on plasma amino-acid levels in healthy people. A randomized double-blind cross-over trial (UMIN000044791) was conducted with a sample of nine healthy individuals. These participants ingested soy protein with or without 42 mg EMIQ for 7 days after performing mild exercise. Plasma amino-acid levels were measured before ingestion and at 15, 30, 45, 60, 90, 120, 180, and 240 min after ingestion on the last day. The concentrations of total amino acids at 0 and 120 min and easily oxidized amino acids at 120 min were significantly higher in the plasma of individuals who consumed 42 mg EMIQ. Oxidative stress levels were lower and plasma testosterone levels were higher in participants who ingested soy protein with 42 mg EMIQ than in those who did not. These results suggest that daily ingestion of soy protein with 42 mg EMIQ can be useful for effective protein absorption.

Amide-Based Ionic Liquid Electrolytes for Alkali-Metal-Ion Rechargeable Batteries.

Ionic liquids (ILs) have a wide variety of applications in energy storage and material production. ILs are composed of only cations and anions, without any molecular solvents, and are generally known as "designer liquids (solvents)" because their physicochemical properties can be tuned by the combination of ionic species. In recent several decades, research and development activities of rechargeable batteries have garnered considerable attention because certain groups of ILs exhibit high electrochemical stability and moderate ionic conductivity, rendering them suitable for application in high-voltage batteries. ILs with amide anions are representative electrolytes and are extensively researched by many research groups, including our group. This paper focuses on amide-based ILs as electrolytes for alkali-metal-ion rechargeable batteries, introducing their history, characteristics, and existing challenges to be addressed.

In vitro and in vivo immune assessments of genetically-engineered pig skin grafts in New World (squirrel) monkeys.

Half a million patients in the USA alone require treatment for burns annually. Following an extensive burn, it may not be possible to provide sufficient autografts in a single setting. Genetic manipulations (GM) of pigs offer the possibility of reducing primate humoral and cellular rejection of pig skin xenografts and thus extending graft survival. We compared the survival of skin grafts from pigs with 9-GM with that of autografts and allografts in squirrel monkeys. Monitoring for rejection was by (1) macroscopic examination, (2) histopathological examination of skin biopsies, and (3) measurement of anti-monkey and anti-pig IgM and IgG antibodies. Autografts (n = 5) survived throughout the 28 days of follow-up without histopathological features of rejection. Median survival of allografts (n = 6) was 14 days and of pig xenografts (n = 12) 21 days. Allotransplantation was associated with an increase in anti-monkey IgM, but the anticipated subsequent rise in IgG had not yet occurred at the time of euthanasia. Pig grafts were associated with increases in anti-pig IgM and IgG. In all cases, histopathologic features of rejection were similar. 9-GM pig skin xenografts survive at least as long as monkey skin allografts (and trended to survive longer), suggesting that they are a realistic clinical option for the temporary treatment of burns. Although monkeys with pig skin grafts developed anti-pig IgM and IgG antibodies, these did not cross-react with monkey antigens, indicating that a primary 9-GM pig skin graft would not be detrimental to a subsequent monkey skin allograft.

Impact of donor sex on hepatocellular carcinoma recurrence in liver transplantation after brain death.

BACKGROUND: Hepatocellular carcinoma (HCC) is predominantly seen in males but has a better prognosis in females. No prior studies have investigated HCC recurrence based on sex combination following liver transplant donated after brain death (DBDLT). This study sought to elucidate the effects of donor and recipient sex on HCC recurrence rates. METHODS: 9232 adult recipients from the United Network for Organ Sharing (UNOS) database who underwent DBDLT for HCC from 2012 to 2018 were included. Donor-recipient pairs were divided into (1) female donor/female recipient (F-F) (n = 1089); (2) male donor/female recipient (M-F) (n = 975); (3) female donor/male recipient (F-M) (n = 2691); (4) male donor/male recipient (M-M) (n = 4477). The primary prognostic outcome was HCC recurrence. A multivariable competing risk regression analysis was used to assess prognostic influences. RESULTS: The median recipient age and model for end-stage liver disease (MELD) scores were similar among the four groups. Livers of male recipients demonstrated greater in size and number of HCC (both p-values were <.0001). There was also a higher rate of vascular invasion in male recipients compared to female (p < .0001). Competing risk analyses showed that the cumulative HCC recurrence rate was significantly lower in the M-F group (p = .013). After adjusting for tumor characteristics, liver grafts from male donors were associated with a lower HCC recurrence rate in female recipients (HR: .62 95%CI: .42-.93) (p = .021). CONCLUSION: In DBDLT, male donor to female recipient pairing exhibited lower HCC recurrence rates. SUMMARY: Lowest rates of HCC recurrence were confirmed among the female recipients of male donor grafts group in the deceased donor LT cohort. A competing risk multivariable regression analysis demonstrated that male donor sex was significantly associated with low HCC recurrence in female but not male recipients.

Smartphone-Enabled Web-Based Simulation of Cellular Neurophysiology for Laboratory Course and its Effectiveness.

The introduction of computer simulations has enhanced the teaching of neurobiology. Many simulators for personal computers are available, but in countries where schools have low school information and communication technology readiness, it is difficult to introduce computer simulations. Even in such countries, however, students often have their own smartphones and are good at operating them. Therefore, we have developed five web-based simulators that cover a wide range of neurophysiology, including single and whole-cell channel currents, membrane potentials and generation and conduction of action potentials using HTML5 and JavaScript. These simulators may be run free of charge on any device, regardless of the model or OS, thereby enabling schools that have no experience in introducing simulations to introduce them easily. These simulators were especially useful in many schools during COVID-19 restrictions. In this paper, we explain the functions of the simulators we have developed and introduce some practical examples. To verify the usefulness of the simulators, we also conducted a survey in the classrooms in which the simulators were used. Understanding and motivation to learn was shown to increase significantly, indicating that these are useful for neurobiology education.

Visualization of the saccule and utricle with non-contrast-enhanced FLAIR sequences.

OBJECTIVES: 3D-fluid attenuation inversion recovery (FLAIR) collected 4 h after intravenous gadolinium injection can delineate the perilymphatic space (PLS) from the endolymphatic space (ELS) to capture endolymphatic hydrops, the pathological counterpart of Ménière's disease. We aimed to optimize visualization of such inner ear internal anatomy using 3D-FLAIR without injection. METHODS: 3D-FLAIR signal from different fluid compartments such as PLS and ELS was first simulated. Then, twenty-two healthy subjects were scanned at 3.0-T MRI with non-injected 3D-FLAIR using variable T2 preparations (T2Preps) (OFF, 200, 400, and 600 ms) and variable inversion times (TIs) (from 224 to 5000 ms) and different resolutions (1.0 × 1.0 × 1.5, 0.6 × 0.6 × 0.8, and 0.6 × 0.6 × 0.6 mm3). The relative contrast between PLS and ELS and the visibility of the saccule and utricle were assessed. Additionally, non-injected 3D-FLAIR with the optimal setting was tested in a Ménière patient and compared with gadolinium-injected 3D-FLAIR. RESULTS: The PLS and ELS were differentiated when T2Prep was used but not without. The relative contrast was larger with T2Prep at 400 ms than at 200 or 600 ms (0.72 ± 0.22 vs. 0.44 ± 0.11, p = 0.019; and 0.72 ± 0.22 vs. 0.46 ± 0.28, p = 0.034, respectively). The saccule and utricle were best delineated in 87. % cases with T2Prep = 400 and TI = 2100 ms at the highest resolution. Visualization of the saccule and utricle in the optimized non-injected 3D-FLAIR was similar to conventional injected 3D-FLAIR in a patient. CONCLUSIONS: Combining a specific T2Prep and TI in non-injected 3D-FLAIR could separate PLS and ELS and even the saccule and utricle, paving the way toward future application to diagnose Ménière's disease. KEY POINTS: • MRI can capture the internal anatomy of inner ear without injection of contrast media. • Specific parameters consisting of a T2 preparation of 400 ms and an inversion time of 2100 ms must be used to visualize the saccule and utricle on non-injected 3D-FLAIR.

The first clinical pig heart transplant: Was IVIg or pig cytomegalovirus detrimental to the outcome?

The clinical course of the first patient to receive a gene-edited pig heart transplant was recently reported by the University of Maryland team. Although the pig heart functioned well for >40 days, serum anti-pig antibodies then increased, and the patient sadly died after 60 days. Because of his debilitated pre-transplant state, the patient never thrived despite excellent graft function for several weeks, and the cause of his demise continues to be uncertain. A few days before an increase in anti-pig antibodies was observed, the patient had received intravenous human immunoglobulin (IVIg), and whether this played a role in his cardiac deterioration has been discussed. Furthermore, mcfDNA testing indicated an increase in pig cytomegalovirus (CMV), and its possible role in the development of cardiac dysfunction has also been considered. On the basis of the limited data provided in the publication and on our previous investigations into whether IVIg contains anti-TKO pig antibodies and therefore might be deleterious to TKO pig organ xenografts, we suggest that the steady rise in anti-pig antibody titer was more consistent with the failure of the immunosuppressive regimen to prevent elicited anti-TKO pig antibody production, rather than from the passive transfusion of IVIg or the presence of pig CMV in the graft. Although the outcome of the Maryland experience was disappointing, valuable lessons were learned. Our attention was drawn to the potential risks of heart transplantation in a "deconditioned" patient, the administration of IVIg, the transmission of pig CMV, and of the difficulties in interpreting myocardial biopsy findings.

Preparation of Li-Excess and Li-Deficient Antiperovskite Structured Li2+xOH1-xBr and Their Effects on Total Ionic Conductivity.

This paper describes about the effect of Li-H exchange amount on total lithium-ion (Li+) conductivity of Li2+xOH1-xBr (x = -0.5 to +0.4). These samples are systematically prepared at room temperature by a dry ball-milling process using LiOH, LiOH·H2O, Li2O, and LiBr as starting materials. Synchrotron X-ray diffraction analysis reveals that single-phase Li2+xOH1-xBr samples are formed within x = -0.5 to +0.35. For improving total Li+ conductivity (σt), a larger x value increases both the Li carrier density and lattice constant as positive factors, while that decreases both the crystallite size and OH rotational unit possibly assisting Li+ conduction as negative factors. This trade-off provides an optimized σt of 3.6 × 10-6 S cm-1 at the Li-excess Li2.2OH0.8Br composition, which is ca. 3 times higher than pristine Li2OHBr (1.1 × 10-6 S cm-1). The hydrogen incorporation into the lattice is confirmed by neutron diffraction analysis, and the refined composition is almost consistent with the prepared composition.

Fecal Diversion in Complex Perianal Fistulizing Crohn's Disease.

Complex perianal Crohn's disease (CD) remains a challenging problem. Fecal stream is thought to be a trigger of disease progression in patients with CD. In patients with refractory perianal CD, diversion of fecal stream is sometimes required to alleviate clinical symptoms when medical and local surgical management are unsuccessful. Several studies evaluated the outcomes of fecal diversion for complex perianal CD. After fecal diversion, the majority of patients achieved early clinical response, but the prospect of restoring bowel continuity was low (approximately 20%). Nearly half of the patients eventually required proctectomy. A number of studies attempted to identify predictive factors for the outcomes of fecal diversion. Only rectal involvement was associated with unsuccessful restoration of bowel continuity. Biologic therapy did not seem to improve the efficacy of fecal diversion, although the evidence level was low because of insufficient data or methodological limitations. Based on these results, fecal diversion may be useful in alleviating clinical symptoms related to severe perianal CD and avoiding immediate proctectomy. The impact of biologic therapy on the outcomes of fecal diversion should be further investigated.

Initial experimental experience of triple-knockout pig red blood cells as potential sources for transfusion in alloimmunized patients with sickle cell disease.

BACKGROUND: Blood transfusion remains important in the treatment of patients with sickle cell disease (SCD). However, alloimmunization after blood transfusion is associated with patient morbidity and mortality. Triple-knockout (TKO) pigs (i.e., pigs in which the three known xenoantigens to which humans have anti-pig antibodies have been deleted) may be an alternative source of RBCs for these patients because many humans have no preformed antibodies to TKO pig RBCs (pRBCs). METHODS AND MATERIALS: In an in vitro study, plasma from alloimmunized (n = 12) or non-alloimmunized (n = 12) SCD patients was used to determine IgM/IgG binding to, and CDC of, TKO pRBCs. In an in vivo study, after an estimated 25% of blood volume was withdrawn from two capuchin monkeys, CFSE-labeled TKO pRBCs were transfused. Loss of TKO pRBCs was monitored by flow cytometry, and 7 weeks later, 25% of blood was withdrawn, and CFSE-labeled monkey RBCs were transfused. RESULTS: The in vitro study demonstrated that plasma from neither alloimmunized nor non-alloimmunized SCD patients bound IgM/IgG to, or induced CDC of, TKO pRBCs. In the in vivo study, survival of TKO pRBCs in the two capuchin monkeys was of 5 and 7 days, respectively, whereas after allotransfusion, survival was >28 days. CONCLUSIONS: In conclusion, (1) in the present limited study, no antibodies were detected that cross-reacted with TKO pRBCs, and (2) TKO pigs may possibly be an alternate source of RBCs in an emergency if no human RBCs are available.

Evidence that sensitization to triple-knockout pig cells will not be detrimental to subsequent allotransplantation.

The current evidence is that sensitization to a pig xenograft does not result in the development of antibodies that cross-react with alloantigens, and therefore, sensitization to a pig xenograft would not be detrimental to the outcome of a subsequent allograft. This evidence relates almost entirely to the transplantation of cells or organs from wild-type or α1,3-galactosyltransferase gene-knockout (GTKO) pigs. However, it is not known whether recipients of triple-knockout (TKO) pig grafts who become sensitized to TKO pig antigens develop antibodies that cross-react with alloantigens and thus be detrimental to a subsequent organ allotransplant. We identified a single baboon (B1317) in which no (or minimal) serum anti-TKO pig antibodies could be measured-in our experience unique among baboons. We sensitized it by repeated subcutaneous injections of TKO pig peripheral blood mononuclear cells (PBMCs) in the absence of any immunosuppressive therapy. After TKO pig PBMC injection, there was a transient increase in anti-TKO pig IgM, followed by a sustained increase in IgG binding to TKO cells. In contrast, there was no serum IgM or IgG binding to PBMCs from any of a panel of baboon PBMCs (n = 8). We conclude that sensitization to TKO pig PBMCs in the baboon did not result in the development of antibodies that also bound to baboon cells, suggesting that there would be no detrimental effect of sensitization on a subsequent organ allotransplant.