Search

Study Question: What are the characteristics of spontaneous endometriosis in cynomolgus monkeys?Summary Answer: Spontaneous endometriosis in cynomolgus monkeys exhibited similar characteristics to the human disease.What Is Known Already: One previous report described the prevalence and the basic histopathology of spontaneous endometriosis in cynomolgus monkeys.Study Design, Size, Duration: Endometriotic lesions that had been histologically confirmed in 8 female cynomolgus monkeys between 5 and 21 years old were subjected to study.Participants/materials, Setting, Methods: The monkeys died of, or were sacrificed because of, sickness consequent on endometriosis. Specimens were evaluated histopathologically with haematoxylin and eosin staining, iron staining and immunohistochemistry (CD10, CD31, α-SMA and PGP9.5), and by observing them under a microscope.Main Results and the Role Of Chance: Endometriotic and stromal cells (CD10-positive) with haemorrhage and inflammation were observed. Smooth muscle metaplasia and nerve fibres were also noted in the endometriotic lesions. Endometriotic lesions in lymph nodes were incidentally found.Limitations and Reasons For Caution: Since laparoscopic analysis for monitoring the disease state was not set as a parameter of the current study, time course changes (progression) of the disease were not assessed.Wider Implications Of the Findings: Further investigation of spontaneous endometriosis in cynomolgus monkeys may contribute to better understanding of the disease pathobiology.Study Funding/competing Interests: No external funds were used for this study. A.N.K., S.M., S.H., T.I., O.K., A.K. and M.S. are full-time employees of Chugai Pharmaceutical Co., Ltd. R.K. received lecture fees from Chugai Pharmaceutical Co., Ltd., unrelated to the submitted work. S.N., S. O., L.Y., K.Y. and T.S. have nothing to declare.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Abstract: Previously, the renal and liver transplantation registry in Japan was enforced yearly using registration and tracking papers only on recipients. The input of all patient data and announcement of statistical analysis to the public required a long time. Following The Declaration of Istanbul 2008, the committees planned to establish new registry and tracking systems for renal and liver transplantations on both recipients and donors. As the first step, for renal transplantation, we established a new registry and tracking system, JARTRE (JApan Renal Transplantation REgistry), using flash (USB) memory in 2009. The recipient and donor data were inputted into the USB memory in the transplantation centers. The memory was collected once a year by the committees with performed at 3 months at 1 year and every year after, the operation. As the second step, for liver transplantation, we established an online registry and tracking system, LITRE-J (LIver Transplantation REgistry in Japan), using the Internet in 2011. The recipient and donor data are inputted online in the centers just after transplantation. The tracking is performed at 3 months, at 1 year and every year after the operation. In 2012, we will convert the JARTRE system to an online registration and tracking system using the Internet like LITRE-J. The advantages of these system are the ease of input, scope of the data, and rapidly for statistical processing. Herein we have reported the details of JARTRE and LITRE-J, as well as the evaluation of the registry and tracking systems for renal and liver transplantation in Japan. [Copyright &y& Elsevier]

Abstract: Following The Declaration of Istanbul 2008, a registration committees of The Japan Society for Transplantation and The Japanese Society for Clinical Renal Transplantation planned to establish a new registry and tracking system for renal transplant recipients and donors supported by a Health Labor Sciences Research Grant by The Ministry of Health Labour and Welfare. In place of the previous paper-based system, we established the new registry and tracking system, JARTRE (Japan Renal Transplantation Registry), using USB memory in 2009. Recipient and donor data were inputted into the USB memory at the transplantation centers. The memory was reviewed a yearly by committees. The recipient and donor registration included details from both. The tracking is performed centrally 3 months, 1 year, and every year after the operation. The advantages of this system are the ease of input, adequacy of the data, and rapid statistical processing. In 2009, we registered 97.9% of new renal transplantation recipients and donors; in 2008 it was more than 81.9% of all past renal transplantation recipients in Japan. [Copyright &y& Elsevier]

Abstract: Laparoscopic nephrectomy (LN) has been accepted for live donor kidney transplantation. Continuous surveys on the status of LN in live donors were made from 2002 to 2008 in Japan. At first, we reported the status in 2008 at 148 Japanese kidney transplantation centers. Of 148 centers, 109 responded, and 58 performed LN. These centers performed 764 live donor nephrectomies, including 659 LN and 105 open nephrectomies. In 58 centers, 20 were performed as hand-assisted (HA) LN, 27 as non-HA (pure laparoscopic), 2 as both HA and non-HA, and 8 as laparoscope-assisted. There were 24 centers that carried out a peritoneal approach and 34 had a retro-peritoneal approach. Among 764 LN donors, not 1 had a life-threatening complication. Blood transfusions were performed in only 1 donor. Open conversions from LN were required in 13 (2.0%) cases. Minor complications not requiring a prolonged hospital stay were reported in 20 cases. The mortality after LN was 0. Among 659 recipients, 1 case was reported as primary nonfunction, but ten recipients (1.5%) needed hemodialysis after transplantation because of delayed graft function. Urinary tract complications were noted in 18 recipients (2.7%). We have discussed the trends in LN from 2002 to 2008 in Japan. At the beginning of LN, many surgeons performed LN, so the open conversion rate was low and the blood transfusion rate was high. But in the later years, surgeons performed LN in the same manner as general laparoscopic surgeries with high intention for donor safety. [Copyright &y& Elsevier]

Abstract: Mycophenolate mofetil (MMF) is used for immunosuppression after organ transplantation, but gastrointestinal side effects including diarrhea are sometimes observed with this drug. We sought to construct on animal model of diarrhea with MMF in rodents. Materials and Methods: BALB/Cj mice, weighing 25 g received 500 mg /kg of MMF, 60 mg/kg of levofloxacin (LVFX), 1000 mg/kg of Hangeshashin-to (HST), which is traditional Kampo medicine. This cocktail was administered orally to MMF, LVFX, HST, MMF+LVFX, and MMF+LVFX+HST groups for 21 days. We measured the water content fecal collected on days 1, 4, 8, 11, 14, 18, and 21. Feces on day 21 were cultured for identification of fecal flora. Mice were sacrificed on day 21, with blood samples collected to measure mycophenolic acid (MPA) concentrations by HPLC. Jejunum, cecum, and colon were taken for histological evaluation. Results: Significant weight loss of mice and increased fecal water content of were observed in MMF and MMF+LVFX but not in MMF+LVFX+HST groups. Serum MPA levels didn’t differ in MMF-administered groups. Inflammatory changes in intestinal villi were observed in the cecum in MMF and MMF+LVFX groups. A change in fecal flora was observed in LVFX-administered groups. Conclusion: Diarrhea induced by MMF in a rodent model produced inflammatory changes in the cecum. LVFX seemed to change the activity of β-glucuronidase in the fecal flora. HST suppressed fecal softening induced by MMF in this animal model. [Copyright &y& Elsevier]

Donor-specific blood transfusion (DST) was introduced to achieve better graft survival. However, its benefits are controversial considering the immunosuppression of cyclosporine (CYA) or tacrolimus (Tac), and its long-term effects have not been well discussed. Of the 40 patients who received DST with CYA, 3 (7.5%) became cross-match positive. Of the 37 patients with negative cross-match, 34 patients received a one-haplotype-matched kidney and were compared to patients with one-haplotype-matched kidney transplant without preoperative DST (n = 13). Acute rejection within 3 months after transplant was 29.4% in the DST group, and 15.4% in the non-DST group. All rejection episodes were steroid resistant in the non-DST group. If the graft survival rates were calculated excluding non-immunological graft loss, graft survival rate was 91.0 and 72.8% at 5 and 10 years in the DST group, and 83.3% at 5 and 10 years in the non-DST group, respectively. The two graft survival lines converged 7 years and 7 months after transplantation. No beneficial effect of DST was statistically evident under CYA immunosuppression. In terms of the severity of acute rejection or the onset of chronic rejection, DST induced a small benefit, however, which seemed to disappear within 8 years after transplantation.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Celiac axis stenosis is frequently associated with pancreaticoduodenal artery aneurysms. Although the cause of stenosis was not clear in most of the reported cases, compression of the median arcuate ligament of the diaphragm was found to be responsible for the stenosis in 7 of 42 reported cases of this type of aneurysm. We report a case of aneurysm caused by compression of the median arcuate ligament of the diaphragm and celiac plexus. An asymptomatic 43-year-old Japanese man was admitted with a low echoic lesion in the uncus of pancreas. Computed tomographic scan and angiogram revealed stenosis of the celiac axis and two aneurysms in the inferior posterior pancreaticoduodenal artery. The celiac plexus and median arcuate ligament were divided surgically and normal flow was reestablished in the celiac axis. One of the aneurysms was resected and the afferent artery of the other aneurysm was ligated. In the setting of pancreaticoduodenal artery aneurysm associated with celiac axis stenosis, management of stenosis should be considered in addition to local treatment of the aneurysm. In this context, division of median arcuate ligament and celiac plexus or aorto-celiac bypass may normalize the flows in the pancreaticoduodenal arcade and could be effective in preventing aneurysm reformation. [ABSTRACT FROM AUTHOR]

Adenocarcinoma of the small intestine is uncommon. Due to this paucity and the lack of specificity of symptoms, patients are usually seen late in the course of their illness, when curative therapy, mainly represented by extensive surgical resection, is unlikely. The authors report a case of primary well-differentiated tubular adenocarcinoma (T4N0M0) arising in the duodenal limb of a reconstructed Billroth I gastroduodenostomy, 9 years after a distal gastrectomy for signet-ring cell carcinoma of the stomach (T4N0M0). Evidence for excluding the possibility of a recurrence of the primary gastric cancer was based on the different histologic pattern, the long disease-free interval, and other features of the second neoplasm. Relatively early diagnosis of the neoplasm, followed by curative surgical therapy was made possible by the early onset of the obstructive symptoms and the favorable anatomical location of the tumor. [ABSTRACT FROM AUTHOR]

A case of extensive extra- and intrahepatic portal tumor thrombosis, with no metastatic foci in liver parenchyma, secondary to advanced gastric carcinoma in a 69-year-old man is reported. The portal tumor thrombosis was characterized by enlargement of the thrombosed segment of the vein, decreased density mass without intraluminal enhancement of the involved vein, nonvisualization of the portal venous branch in the involved lobe, and the so-called cavernous transformation of the portal vein. The surgically resected gastric specimen showed Borrmann type 3 advanced papillary adenocarcinoma. The portal tumor thrombus is presumed to have arisen from vascular invasion in the primary foci of gastric carcinoma, and then to have permeated the portal vein without invasion of liver parenchyma. [ABSTRACT FROM AUTHOR]

Abstract: In three hospitals within a restricted area in Japan in November, 2006, 42 patients were revealed to have received kidneys transplanted from unrelated living donors who displayed renal diseases. All of these cases were performed by one doctor without any ethical discussion in the hospitals nor any reports to the public. Almost all medical records were discarded legally in two hospitals. Only one hospital, Uwajima City Hospital, kept the almost complete records including the survivals of 25 cases. The Japan Society for Transplantation was asked to analyze these cases leading to this report on the long-term outcome of cases at Uwajima City Hospital. The diseased kidney grafts were procured in four hospitals. The cases of removal of the kidneys from the donors were malignant diseases (n = 11) or benign diseases (n = 14). The survival rates of the donors were 86.1% at 1, 70.8% at 5, and 57.7% at 10 years. The survival rates of the recipients transplanted from donors with malignant versus benign diseases were 80.8% versus 92.3% in 1, 48.5% versus 84.6% at 5% and 48.5% versus 76.2% at 10 years, respectively. The survival rates of the grafts from donors with malignant versus benign diseases were 71.6% versus 71.4% at 1, 15.3% versus 50.0% at 5, and 15.3% versus 33.3% at 10 years, respectively. In conclusion, we have reported herein the low survival rates of renal transplantation recipients and grafts from unrelated living donors with preexistent renal diseases. [Copyright &y& Elsevier]

Abstract: The increased acceptance of laparoscopic nephrectomy (LN) has been a driving force for live donor kidney transplantation. However, the outcomes of LN in live donors has not yet been clarified in Japan. In this study, we surveyed 125 Japanese kidney transplantation centers to investigate the current status of live donor LN. Of 125 centers, the 98 that responded had performed 695 live donor nephrectomies. Among these centers, 43 had performed LN. Among the 695 nephrectomies, 441 donors had undergone LN and 254, open nephrectomies. In 43 centers, 16 were performed as hand-assisted (HA) LN; 20, non-HA; 3, both HA and non-HA; and 5 laparoscope-assisted. Ten centers used a peritoneal approach; 30, a retroperitoneal; and 3, both. In 441 LN donors, 1 had a life-threatening complication of deep venous thrombosis and survived. Blood transfusions were performed in 7 donors. Open conversions from LN were necessary in 24. Minor complications not requiring prolonged hospital stay were reported in 52. The mortality of LN was zero. In contrast, among the 441 recipients, 1 case was reported as primary nonfunction after venous misadventure in the operation and 30 recipients needed hemodialysis after transplantation because of delayed graft function. Urinary tract complications were noted in 11 recipients. This survey presented the current status of the procedure, providing a base for informed consent from potential donors. [Copyright &y& Elsevier]

Abstract: We performed a multicenter study in Japan to assess the efficacy and safety of immunosuppressive therapy with high-dose mizoribine (MZR; 6 mg/kg) combined with basiliximab (Bas), cyclosporine (CyA), and a corticosteroid in 90 patients. MZR was adjusted to maintain a target trough level of 1 to 2 μg/mL. CyA was started at 7 mg/kg to maintain blood levels in the target therapeutic range of 200 ng/mL (trough [C0]), 1200 ng/mL (2-hour post-dose [C2]), and 6000 ng·h/mL (area under the curve0–9). Bas (20 mg/body weight) was administered on the day of transplantation and on postoperative day 4. Rejection was diagnosed by episode and protocol biopsies. Cytomegalovirus (CMV) antigenemia (direct immunological staining of leukocytes using peroxidase-labeled monoclonal antibody [C7-HRP]) levels were measured every 2 weeks for 6 months. At 12 months, all patients and grafts were surviving except for one death from infection: the 1-year patient and graft survival rate was 98.9%. The acute rejection rate was 21.1%. The mean serum creatinine level at 1 year was 1.51 ± 0.61 mg/dL. The incidence of CMV disease was 0% with 28.9%, CMV antigenemia and 5.6%, ganoyclovir treatment. The incidence of BK virus disease was 2.2%. The mean serum uric acid level was 7.15 ± 1.79 mg/dL at 1 month and 7.06 ± 1.78 mg/dL at 3 months. We observed that a high-dose MZR regimen in combination with CyA, Bas, and corticosteroid was safe and effective to reduce the frequency of CMV and BK virus-related events in renal transplant recipients. [Copyright &y& Elsevier]

Abstract Background It has been reported that transplant recipients are exposed to physical and psychosocial stresses even after transplant surgery and exhibit psychological disorders such as depression. Purpose In this study, we extracted trends concerning how recipients of kidney transplants cope with stress, and we also examined how they cope with depression and its countermeasures. Method We administered questionnaire surveys to 109 kidney transplant recipients. These included items on personal attributes, medical information, depression, and stress-coping type scales. Statistical analysis was performed using factor analysis and multiple regression analysis. Results Fifteen out of 109 (13.8%) were found to be high-risk patients for depression based on responses to the questionnaire using the depression scale. We extracted 2 factors of stress-coping type, namely Factor 1, "Directly coping with the problem," of patients who try to directly resolve the problem in a positive manner and Factor 2, "Stress-release while avoiding the problem," for those who relieve their feelings in response to the stress without resolving the problem itself. When multiple regression analysis was conducted with the depression scale as the dependent variable and the stress-coping factor as the independent variable, Factor 1 tended to be associated with reduced depression and Factor 2 with increased depression. Conclusions Results showed that to improve the mental health of those who receive kidney transplants, it is necessary to examine the depression and stress-coping types of such patients at an early stage and carry out education on stress-coping, focusing on resolving the actual problem. [ABSTRACT FROM AUTHOR]

Mizoribine (MZR) is an immunosuppressive agent that exhibits a less potent immunosuppressive effect at doses up to 3 mg/kg/d. We investigated whether high-dose MZR is effective and safe for renal transplant patients in conjunction with cyclosporine (CsA), basiliximab, and corticosteroids. Ninety Japanese renal transplant patients were administered MZR (6 mg/kg/d), CsA (7 mg/kg/d), prednisolone (maintenance dose, 10 mg/d), and basiliximab (20 mg/body). They were compared with a control group of 81 renal transplant patients who received mycophenolate mofetil (MMF; 1500 mg/d), CsA, prednisolone, and basiliximab. The 2-year patient and graft survival rates were 98.9% and 97.8% in the MZR group and 98.8% and 97.5% in the MMF group, respectively. The rejection rate within 2 years after transplantation was 21.1% in the MZR group and 16.0% in the MMF group; the difference was nonsignificant. None of the MZR group developed cytomegalovirus (CMV) disease, whereas 12.3% of the MMF group contracted CMV ( P < .0001). CMV viremia developed in 28.9% of the MZR group vs 46.9% of the MMF group ( P < .0001); their peak antigen levels were 20.4 ± 44.1 and 252.8 ± 527.0 ( P < .01). Furthermore, the incidence of gastrointestinal disorder, hyperlipidemia, and blood disorder was significantly lower in the MZR group than in the MMF group. The combination of high-dose MZR with CsA, basiliximab, and corticosteroids not only provides satisfactory immunosuppression but is also associated with a low incidence of CMV infection and gastrointestinal and blood disorders. [ABSTRACT FROM AUTHOR]

The excess mortality of coronavirus disease 2019 (COVID-19) solid organ transplant recipients (SOTRs) throughout the pandemic remains unclear. This prospective cohort study based on the Japanese nationwide registry included 1632 SOTRs diagnosed with COVID-19 between February 1, 2020, and July 31, 2022, categorized based on dominant phases of variants of concern (VOCs): Waves 1 to 3 (Beta), 4 (Alpha), 5 (Delta), 6 (Omicron BA.1/BA.2), and 7 (Omicron BA.5). Excess mortality of COVID-19-affected SOTRs was analyzed by calculating standardized mortality ratios (SMRs). Overall, 1632 COVID-19-confirmed SOTRs included 1170 kidney, 408 liver, 25 lung, 20 heart, 1 small intestine, and 8 multiorgan recipients. Although disease severity and all-cause mortality decreased as VOCs transitioned, SMRs of SOTRs were consistently higher than those of the general population throughout the pandemic, showing a U-shaped gap that peaked toward the Omicron BA.5 phase; SMR (95% CI): 6.2 (3.1-12.5), 4.0 (1.5-10.6), 3.0 (1.3-6.7), 8.8 (5.3-14.5), and 21.9 (5.5-87.6) for Waves 1 to 3 (Beta), Wave 4 (Alpha), Wave 5 (Delta), Wave 6 (Omicron BA.1/2), and Wave 7 (Omicron BA.5), respectively. In conclusion, COVID-19 SOTRs had greater SMRs than the general population across the pandemic. Vaccine boosters, immunosuppression optimization, and other protective measures, particularly for older SOTRs, are paramount., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: NPB-22 (quinolin-8-yl 1-pentyl-1H-indazole-3-carboxylate), Adamantyl-THPINACA (N-(1-adamantantyl)-1-[(tetrahydro-2H-pyran-4-yl)methyl]-1H-indazole-3-carboxamide), and CUMYL-4CN-B7AICA (1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)-1H- pyrrolo[2,3-b]pyridine-3-carboxamide), synthetic cannabinoids were evaluated in terms of CB 1 (cannabinoid receptor type 1) and CB 2 (cannabinoid receptor type 2) activities, and their biological effects when inhaled similar to cigarettes were examined., Methods: The half maximal effective concentration values of the aforementioned synthetic cannabinoids at the CB 1 and CB 2 were investigated using [ 35 S]guanosine-5'-O-(3-thio)-triphosphate binding assays. In addition, their biological effects were evaluated using the inhalation exposure test with mice. The smoke generated was recovered by organic solvents in the midget impingers, and the thermal degradation compounds of the smoke components were identified and quantified using a liquid chromatography-photo diode array detector., Results: NPB-22 and Adamantyl-THPINACA had equivalent CB 1 activity in in vitro assays. Meanwhile, NPB-22 had a weaker biological effect on some items on the inhalation exposure test than Adamantyl-THPINACA. When analyzing organic solvents in the midget impingers, it was revealed that NPB-22 was degraded to 8-quinolinol and pentyl indazole 3-carboxylic acid by combustion. In addition, these degradation compounds did not have CB 1 activity., Conclusion: It was estimated that the biological effects of NPB-22 on the inhalation exposure test weakened because it underwent thermal degradation by combustion, and the resultant degradation compounds did not have any CB 1 activity in vitro., (© 2024. The Author(s).)

Poor post-vaccination production of antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a concern among solid organ transplant (SOT) recipients. Furthermore, the timing and kinetics of antibody titers after the second vaccine dose are unknown. We conducted a multicenter prospective observational study that included 614 SOT recipients: 460 kidney, 53 heart, 50 liver, 20 lung, and 31 simultaneous pancreas-kidney (SPK). The participants received two doses of the mRNA vaccine (Pfizer BNT162b2 or Moderna mRNA-1273), as indicated. Serum samples were collected before the first and second vaccinations and at 1, 3, and 6 months after the second vaccine dose, which were then assessed for SARS-CoV-2 antibodies. The overall seropositivity rate was 43% at 1 month after administration of the second vaccine dose; it gradually increased to 68% at 3 months after second dose administration and to 70% at 6 months. In addition, recipient of kidney, lung or SPK transplants had lower antibody titers at the 3- and 6-month time points than did the other recipients. SOT recipients acquired SARS-CoV-2 S-IgG antibodies slowly, and the peak titer differed significantly from that of the general population., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yoshio Hirota reports financial support was provided by Health Labor Administration. Yoshio Hirota reports a relationship with Japan Health Labor Administration that includes: funding grants. The authors of this manuscript have no conflicts of interest to disclose as described by the Vaccine. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Abstract: Transient abnormal myelopoiesis (TAM) is a common complication in newborns with Down syndrome (DS). It commonly progresses to myeloid leukemia (ML-DS) after spontaneous regression. In contrast to the favorable prognosis of primary ML-DS, patients with refractory/relapsed ML-DS have poor outcomes. However, the molecular basis for refractoriness and relapse and the full spectrum of driver mutations in ML-DS remain largely unknown. We conducted a genomic profiling study of 143 TAM, 204 ML-DS, and 34 non-DS acute megakaryoblastic leukemia cases, including 39 ML-DS cases analyzed by exome sequencing. Sixteen novel mutational targets were identified in ML-DS samples. Of these, inactivations of IRX1 (16.2%) and ZBTB7A (13.2%) were commonly implicated in the upregulation of the MYC pathway and were potential targets for ML-DS treatment with bromodomain-containing protein 4 inhibitors. Partial tandem duplications of RUNX1 on chromosome 21 were also found, specifically in ML-DS samples (13.7%), presenting its essential role in DS leukemia progression. Finally, in 177 patients with ML-DS treated following the same ML-DS protocol (the Japanese Pediatric Leukemia and Lymphoma Study Group acute myeloid leukemia -D05/D11), CDKN2A, TP53, ZBTB7A, and JAK2 alterations were associated with a poor prognosis. Patients with CDKN2A deletions (n = 7) or TP53 mutations (n = 4) had substantially lower 3-year event-free survival (28.6% vs 90.5%; P < .001; 25.0% vs 89.5%; P < .001) than those without these mutations. These findings considerably change the mutational landscape of ML-DS, provide new insights into the mechanisms of progression from TAM to ML-DS, and help identify new therapeutic targets and strategies for ML-DS., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)