Author: "Imagawa, A." / Topic: humans - Searchworks@Jio Institute Digital Library Search Results

1,110 results on '"Imagawa, A."'

1. Delayed gastric emptying is associated with increased risk of mortality in patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma

Author: Dominguez, Oscar Hernandez, Grigorian, Areg, Wolf, Ronald F, Imagawa, David K, Nahmias, Jeffry T, and Jutric, Zeljka
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Patient Safety, Digestive Diseases, Clinical Research, Rare Diseases, Cancer, Good Health and Well Being, Humans, Pancreaticoduodenectomy, Pancreatectomy, Gastroparesis, Adenocarcinoma, Pancreatic Neoplasms, Pancreatic Fistula, Postoperative Complications, Risk Factors, Gastric Emptying, Pancreatic fistula, Delayed gastric emptying, Pancreatic cancer
Abstract: Delayed gastric emptying (DGE) is common in patients undergoing pancreaticoduodenectomy (PD). The effect of DGE on mortality is less clear. We sought to identify predictors of mortality in patients undergoing PD for pancreatic adenocarcinoma hypothesizing DGE to independently increase risk of 30-day mortality. The ACS-NSQIP targeted pancreatectomy database (2014-2017) was queried for patients with pancreatic adenocarcinoma undergoing PD. A multivariable logistic regression analysis was performed. Separate sensitivity analyses were performed adjusting for postoperative pancreatic fistula (POPF) grades A-C. Out of 8011 patients undergoing PD, 1246 had DGE (15.6%). About 8.5% of patients with DGE had no oral intake by postoperative day-14. The DGE group had a longer median operative duration (373 vs. 362 min, p = 0.019), and a longer hospital length of stay (16.5 vs. 8 days, p
Published: 2023

2. The modern trauma pancreaticoduodenectomy for penetrating trauma: a propensity-matched analysis.

Author: Grigorian, A, Dosch, AR, Delaplain, PT, Imagawa, D, Jutric, Z, Wolf, RF, Margulies, D, and Nahmias, J
Subjects: Humans, Abdominal Injuries, Wounds, Penetrating, Length of Stay, Pancreatectomy, Pancreaticoduodenectomy, Injury Severity Score, Retrospective Studies, Adult, Mortality, Trauma, Whipple, Rare Diseases, Injury (total) Accidents/Adverse Effects, Clinical Research, Pancreatic Cancer, Cancer, Digestive Diseases, Injuries and accidents, Good Health and Well Being
Abstract: Trauma pancreaticoduodenectomy (TP) remains a challenging operation with morbidity and mortality rates as high as 80% and 50%. Many trauma surgeons consider it surgical dogma to avoid performing a TP during the index operation for patients with severe pancreatic or duodenal injuries. However, there is no modern analysis evaluating this belief. Therefore, we hypothesized no difference in risk of mortality between patients with severe pancreatic or duodenal injury undergoing a TP for penetrating trauma to propensity-matched controls undergoing laparotomy without TP. The Trauma Quality Improvement Program (2010-2016) was queried for adults with severe penetrating pancreatic or duodenal injuries undergoing laparotomy. A 1:2 propensity-matching including demographics/comorbidities, injury severity score, vitals on admission, Glasgow Coma Scale and concomitant injuries for laparotomy with or without TP was performed. Risk of mortality was reported using a univariable logistic regression model. Of 2182 patients with severe pancreatic or duodenal injuries undergoing laparotomy, 54 (2.5%) underwent TP and 2128 (97.5%) underwent laparotomy without TP. There were no differences in propensity-matching characteristics. Patients undergoing TP had a similar mortality rate (20.0% vs. 28.7%, p = 0.302) but a longer length of stay (LOS) (27.5 vs. 16.5 days, p = 0.017). The TP group had a similar associated risk of mortality (OR = 0.62, p = 0.302) but higher risk of major complications (OR 3.44, CI 1.35-17.47, p = 0.015). In appropriately selected penetrating trauma patients with severe pancreatic/duodenal injuries, TP is associated with a similar risk of mortality compared to laparotomy without TP. However, TP patients did have an increased associated risk of major complications and longer LOS.
Published: 2021

3. Effect of home environment on academic achievement in child protective service-involved children: Results from the second national survey of child and adolescent well-being study

Author: Johnson, Jennifer, Perrigo, Judith L, Deavenport-Saman, Alexis, Wee, Choo Phei, Imagawa, Karen Kay, Schonfeld, David J, and Vanderbilt, Douglas
Subjects: Social Work, Human Society, Pediatric, Mind and Body, Behavioral and Social Science, Basic Behavioral and Social Science, Clinical Research, Academic Success, Achievement, Adolescent Health, Caregivers, Child, Child Protective Services, Child, Preschool, Educational Status, Female, Foster Home Care, Humans, Male, Surveys and Questionnaires, Child maltreatment, Academic achievement, Placement, Home environment, Foster care, Child protective services, Criminology, Psychology, Developmental & Child Psychology, Social work, Applied and developmental psychology
Abstract: BackgroundChildren involved with Child Protective Services (CPS) have been shown to have lower academic achievement. It is unclear whether certain qualities of the home environment can optimize academic achievement in this vulnerable population.ObjectiveThis study sought to determine whether home environments with higher levels of emotional support and cognitive stimulation predict later academic achievement and whether this relationship is moderated by placement type (i.e. biological/adoptive parent care, kinship care, or non-kinship foster care).Participants and settingThis study included 1,206 children from the second National Survey of Child and Adolescent Well-Being (NSCAW-II) who were involved with CPS between 2-7 years of age.MethodsMultivariate analyses were completed to examine the effect of the Home Observation for Measurement of the Environment (HOME) score on later Woodcock-Johnson III Tests of Achievement (WJ-ACH) scores. Moderation analyses were conducted to determine the effect of placement type on this relationship.ResultsAlthough these relationships between HOME scores and WJ-ACH scores were significant in bivariate analyses, they were not statistically significant in multivariate analyses, primarily due to the variable of household income. Although children placed primarily in non-kinship foster care demonstrated higher WJ-ACH scores for Passage Comprehension and Letter-Word Identification subscales, placement type did not appear to moderate the relationship between HOME scores and academic achievement.ConclusionChild- and caregiver-level factors, as well as financial resources available in the environment, may account for the relationship between home environment and academic achievement.
Published: 2021

4. DNA Methylation Signature for EZH2 Functionally Classifies Sequence Variants in Three PRC2 Complex Genes

Author: Choufani, Sanaa, Gibson, William T, Turinsky, Andrei L, Chung, Brian HY, Wang, Tianren, Garg, Kopal, Vitriolo, Alessandro, Cohen, Ana SA, Cyrus, Sharri, Goodman, Sarah, Chater-Diehl, Eric, Brzezinski, Jack, Brudno, Michael, Ming, Luk Ho, White, Susan M, Lynch, Sally Ann, Clericuzio, Carol, Temple, I Karen, Flinter, Frances, McConnell, Vivienne, Cushing, Tom, Bird, Lynne M, Splitt, Miranda, Kerr, Bronwyn, Scherer, Stephen W, Machado, Jerry, Imagawa, Eri, Okamoto, Nobuhiko, Matsumoto, Naomichi, Testa, Guiseppe, Iascone, Maria, Tenconi, Romano, Caluseriu, Oana, Mendoza-Londono, Roberto, Chitayat, David, Cytrynbaum, Cheryl, Tatton-Brown, Katrina, and Weksberg, Rosanna
Subjects: Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Rare Diseases, Abnormalities, Multiple, Adolescent, Adult, Child, Child, Preschool, Cohort Studies, Congenital Hypothyroidism, Craniofacial Abnormalities, DNA Methylation, Enhancer of Zeste Homolog 2 Protein, Female, Hand Deformities, Congenital, Humans, Infant, Intellectual Disability, Male, Mosaicism, Mutation, Mutation, Missense, Neoplasm Proteins, Polycomb Repressive Complex 2, Reproducibility of Results, Transcription Factors, Young Adult, DNA methylation signature, EED, SUZ12, intellectual disability, overgrowth syndromes, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract: Weaver syndrome (WS), an overgrowth/intellectual disability syndrome (OGID), is caused by pathogenic variants in the histone methyltransferase EZH2, which encodes a core component of the Polycomb repressive complex-2 (PRC2). Using genome-wide DNA methylation (DNAm) data for 187 individuals with OGID and 969 control subjects, we show that pathogenic variants in EZH2 generate a highly specific and sensitive DNAm signature reflecting the phenotype of WS. This signature can be used to distinguish loss-of-function from gain-of-function missense variants and to detect somatic mosaicism. We also show that the signature can accurately classify sequence variants in EED and SUZ12, which encode two other core components of PRC2, and predict the presence of pathogenic variants in undiagnosed individuals with OGID. The discovery of a functionally relevant signature with utility for diagnostic classification of sequence variants in EZH2, EED, and SUZ12 supports the emerging paradigm shift for implementation of DNAm signatures into diagnostics and translational research.
Published: 2020

5. Systematic review of islet cryopreservation

Author: Kojayan, Greg G, Alexander, Michael, Imagawa, David K, and Lakey, Jonathan RT
Subjects: Transplantation, Autoimmune Disease, Diabetes, Metabolic and endocrine, Animals, Cryopreservation, History, 19th Century, History, 20th Century, History, 21st Century, Humans, Islets of Langerhans, Islets of Langerhans Transplantation, cryopreservation, cryoprotectant, pancreatic islets, transplantation, islet freezing, islet thawing, diabetes, Islet cell biology, physiology, Islet cell biology/physiology, Medical Microbiology, Medical Physiology
Abstract: Pancreatic islet transplantation is being extensively researched as an alternative treatment for type 1 diabetic patients. This treatment is currently limited by temporal mismatch, between the availability of pancreas and isolated islets from deceased organ donor, and the recipient's need for freshly isolated islets. To solve this issue, cryopreservation of islets may offer the potential to bank islets for transplant on demand. Cryopreservation, however, introduces an overwhelmingly harsh environment to the ever-so-fragile islets. After exposure to the freezing and thawing, islets are usually either apoptotic, non-functional, or non-viable. Several studies have proposed various techniques that could lead to increased cell survival and function following a deep freeze. The purpose of this article is to critically review the techniques of islet cryopreservation, with the goal of highlighting optimization parameters that can lead to the most viable and functional islet upon recovery and/or transplant.
Published: 2018

6. Value of the portal venous phase in evaluation of treated hepatocellular carcinoma following transcatheter arterial chemoembolisation

Author: Lam, A, Fernando, D, Sirlin, CC, Nayyar, M, Goodwin, SC, Imagawa, DK, and Lall, C
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Liver Cancer, Liver Disease, Rare Diseases, Biomedical Imaging, Digestive Diseases, Adult, Aged, Aged, 80 and over, Carcinoma, Hepatocellular, Chemoembolization, Therapeutic, Female, Humans, Liver Neoplasms, Magnetic Resonance Imaging, Male, Middle Aged, Portal Vein, Retrospective Studies, Tomography, X-Ray Computed, Treatment Outcome, Nuclear Medicine & Medical Imaging, Clinical sciences
Abstract: AimTo evaluate the utility of the portal venous phase on multiphasic computed tomography (CT) after treatment of hepatocellular carcinoma (HCC) with trans-arterial chemoembolisation (TACE).Materials and methodsThis was a retrospective review of patients who underwent TACE for HCC between 1 April 2012 and 21 December 2014, with appropriate multiphasic, pre- and post-procedural CT examinations. The maximum non-contrast, arterial phase, and portal venous phase attenuation values of the tumour and tumour bed were evaluated within a region of interest (ROI), with values adjusted against background hepatic parenchyma. Linear regression analyses were performed for both the arterial and venous phases, to assess the level of enhancement and to determine if the venous phase had additional value in this setting.ResultsA total of 86 cases from 51 patients were reviewed. All pre-procedural CT examinations of lesions demonstrated arterial phase enhancement with portal venous and delayed phase washout compatible with HCC. The post-procedural CT examinations following TACE revealed expected decreased arterial enhancement. Sixty-five cases (76%) showed persistent non-enhancement on the portal venous phase following embolisation therapy. A total of 21 cases (24%), however, demonstrated progressive portal venous hyper enhancement. Linear regression analysis demonstrated a statistical significance between the difference in maximal arterial and portal venous enhancement in these cases.ConclusionFollowing TACE, the treated lesion may demonstrate portal venous phase hyper-enhancement within the tumour bed. As such, full attention should be given to these images for comprehensive evaluation of tumour response following treatment.
Published: 2017

7. Closed-loop assisted versus manual goal-directed fluid therapy during high-risk abdominal surgery: a case-control study with propensity matching.

Author: Rinehart, Joseph, Lilot, Marc, Lee, Christine, Joosten, Alexandre, Huynh, Trish, Canales, Cecilia, Imagawa, David, Demirjian, Aram, and Cannesson, Maxime
Subjects: Abdomen, Humans, Blood Loss, Surgical, Cardiac Output, Stroke Volume, Monitoring, Intraoperative, Fluid Therapy, Resuscitation, Anesthesia, General, Digestive System Surgical Procedures, Case-Control Studies, Feasibility Studies, Heart Rate, Aged, Middle Aged, Guideline Adherence, Female, Male, Hemodynamics, Propensity Score, Emergency & Critical Care Medicine, Medical and Health Sciences
Abstract: IntroductionGoal-directed fluid therapy strategies have been shown to benefit moderate- to high-risk surgery patients. Despite this, these strategies are often not implemented. The aim of this study was to assess a closed-loop fluid administration system in a surgical cohort and compare the results with those for matched patients who received manual management. Our hypothesis was that the patients receiving closed-loop assistance would spend more time in a preload-independent state, defined as percentage of case time with stroke volume variation less than or equal to 12%.MethodsPatients eligible for the study were all those over 18 years of age scheduled for hepatobiliary, pancreatic or splenic surgery and expected to receive intravascular arterial blood pressure monitoring as part of their anesthetic care. The closed-loop resuscitation target was selected by the primary anesthesia team, and the system was responsible for implementation of goal-directed fluid therapy during surgery. Following completion of enrollment, each study patient was matched to a non-closed-loop assisted case performed during the same time period using a propensity match to reduce bias.ResultsA total of 40 patients were enrolled, 5 were ultimately excluded and 25 matched pairs were selected from among the remaining 35 patients within the predefined caliper distance. There was no significant difference in fluid administration between groups. The closed-loop group spent a significantly higher portion of case time in a preload-independent state (95 ± 6% of case time versus 87 ± 14%, P =0.008). There was no difference in case mean or final stroke volume index (45 ± 10 versus 43 ± 9 and 45 ± 11 versus 42 ± 11, respectively) or mean arterial pressure (79 ± 8 versus 83 ± 9). Case end heart rate was significantly lower in the closed-loop assisted group (77 ± 10 versus 88 ± 13, P =0.003).ConclusionIn this case-control study with propensity matching, clinician use of closed-loop assistance resulted in a greater portion of case time spent in a preload-independent state throughout surgery compared with manual delivery of goal-directed fluid therapy.Trial registrationClinicalTrials.gov Identifier: NCT02020863. Registered 19 December 2013.
Published: 2015

8. Composite liver tumors: a radiologic-pathologic correlation.

Author: Nayyar, Megha, Imagawa, David K, Tirkes, Temel, Demirjian, Aram N, Houshyar, Roozbeh, Sandrasegaran, Kumar, Nangia, Chaitali S, Seery, Tara, Bhargava, P, Choi, Joon Ii, and Lall, Chandana
Subjects: Humans, Carcinoma, Hepatocellular, Cholangiocarcinoma, Liver Neoplasms, alpha-Fetoproteins, CA-19-9 Antigen, Tomography, X-Ray Computed, Magnetic Resonance Imaging, Risk Factors, Survival Analysis, Phenotype, Bi-phenotypic tumors, Computed tomography, Magnetic resonance imaging, Hepatoceullular carcinoma, Carcinoma, Hepatocellular, Tomography, X-Ray Computed, Computed tomography, Magnetic resonance imaging
Abstract: Bi-phenotypic neoplasm refers to tumors derived from a common cancer stem cell with unique capability to differentiate histologically into two distinct tumor types. Bi-phenotypic hepatocellular carcinoma-cholangiocarcinoma (HCC-CC), although a rare tumor, is important for clinicians to recognize, since treatment options targeting both elements of the tumor are crucial. Imaging findings of bi-phenotypic HCC-CC are not specific and include features of both HCC and CC. A combination of imaging and immuno-histochemical analysis is usually needed to make the diagnosis.
Published: 2014

9. Magnetic resonance imaging following treatment of advanced hepatocellular carcinoma with sorafenib.

Author: Bhosale, Priya, Bhargava, Puneet, Tirkes, Temel, Seery, Tara, Lall, Chandana, Choi, Joon-Il, and Imagawa, David
Subjects: Hepatocellular carcinoma, MRI, Sorafenib, mRECIST, Aged, Antineoplastic Agents, Carcinoma, Hepatocellular, Female, Humans, Liver Neoplasms, Magnetic Resonance Imaging, Male, Middle Aged, Niacinamide, Phenylurea Compounds, Sorafenib, Tomography, X-Ray Computed
Abstract: Hepatocellular carcinomas are highly vascular tumors, showing progressive hypervascularity by the process of neoangiogenesis. Tumor angiogenesis is critical for tumor growth as well as metastatic spread therefore, imaging and quantification of tumor neo-angiogenesis is essential for monitoring response to targeted therapies and predicting disease progression. Sorafenib is a molecular targeting agent used for treating hypervascular tumors. This drug is now the standard of care in treatment of patients with advanced hepatocellular carcinoma. Due to its anti-angiogenic and anti-proliferative actions, imaging findings following treatment with Sorafenib are quite distinct when compared to conventional chemotherapeutic agents. Liver MRI is a widely adopted imaging modality for assessing treatment response in hepatocellular carcinoma and imaging features may reflect pathophysiological changes within the tumor. In this mini-review, we will discuss MRI findings after Sorafenib treatment in hepatocellular carcinoma and review the feasibility of MRI as an early biomarker in differentiating responders from non-responders after treatment with molecular targeting agents.
Published: 2014

10. Magnetic resonance imaging following treatment of advanced hepatocellular carcinoma with sorafenib.

Author: Choi, Joon-Il, Imagawa, David K, Bhosale, Priya, Bhargava, Puneet, Tirkes, Temel, Seery, Tara E, and Lall, Chandana
Subjects: Humans, Carcinoma, Hepatocellular, Liver Neoplasms, Phenylurea Compounds, Niacinamide, Antineoplastic Agents, Tomography, X-Ray Computed, Magnetic Resonance Imaging, Aged, Middle Aged, Female, Male, Hepatocellular carcinoma, MRI, Sorafenib, mRECIST
Abstract: Hepatocellular carcinomas are highly vascular tumors, showing progressive hypervascularity by the process of neoangiogenesis. Tumor angiogenesis is critical for tumor growth as well as metastatic spread therefore, imaging and quantification of tumor neo-angiogenesis is essential for monitoring response to targeted therapies and predicting disease progression. Sorafenib is a molecular targeting agent used for treating hypervascular tumors. This drug is now the standard of care in treatment of patients with advanced hepatocellular carcinoma. Due to its anti-angiogenic and anti-proliferative actions, imaging findings following treatment with Sorafenib are quite distinct when compared to conventional chemotherapeutic agents. Liver MRI is a widely adopted imaging modality for assessing treatment response in hepatocellular carcinoma and imaging features may reflect pathophysiological changes within the tumor. In this mini-review, we will discuss MRI findings after Sorafenib treatment in hepatocellular carcinoma and review the feasibility of MRI as an early biomarker in differentiating responders from non-responders after treatment with molecular targeting agents.
Published: 2014

11. Surgery for Gallstone Ileus

Author: Halabi, Wissam J, Kang, Celeste Y, Ketana, Noor, Lafaro, Kelly J, Nguyen, Vinh Q, Stamos, Michael J, Imagawa, David K, and Demirjian, Aram N
Subjects: Patient Safety, Clinical Research, Aging, Digestive Diseases, Evaluation of treatments and therapeutic interventions, 6.4 Surgery, Oral and gastrointestinal, Aged, Aged, 80 and over, Biliary Fistula, Cholecystectomy, Databases, Factual, Digestive System Surgical Procedures, Female, Gallstones, Hospital Mortality, Humans, Incidence, Intestinal Fistula, Intestinal Obstruction, Intestine, Small, Logistic Models, Male, Multivariate Analysis, Postoperative Complications, Retrospective Studies, Treatment Outcome, United States, biliary, bilioenteric fistula, bowel obstruction, gallstone ileus, Medical and Health Sciences, Surgery
Abstract: IntroductionGallstone ileus is a mechanical bowel obstruction caused by a biliary calculus originating from a bilioenteric fistula. Because of the limited number of reported cases, the optimal surgical method of treatment has been the subject of ongoing debate.MethodsA retrospective review of the Nationwide Inpatient Sample from 2004 to 2009 was performed for gallstone ileus cases treated surgically by enterotomy with stone extraction alone (ES), enterotomy and cholecystectomy with fistula closure (EF), bowel resection alone (BR), and bowel resection with fistula closure (BF). Patient demographics, hospital factors, comorbidities, and postoperative outcomes were reported. Multivariate analysis was performed comparing mortality, morbidity, length of stay, and total cost for the different procedure types.ResultsOf the estimated 3,452,536 cases of mechanical bowel obstruction from 2004 to 2009, 3268 (0.095%) were due to gallstone ileus-an incidence lower than previously reported. The majority of patients were elderly women (>70%). ES was the most commonly performed procedure (62% of patients) followed by EF (19% of cases). In 19%, a bowel resection was required. The most common complication was acute renal failure (30.44% of cases). In-hospital mortality was 6.67%. On multivariate analysis, EF and BR were independently associated with higher mortality than ES [(odds ratio [OR] = 2.86; confidence interval [CI]: 1.16-7.07) and (OR = 2.96; CI: 1.26-6.96) respectively]. BR was also associated with a higher complication rate, OR = 1.98 (CI: 1.13-3.46).ConclusionsGallstone ileus is a rare surgical disease affecting mainly the elderly female population. Mortality rates appear to be lower than previously reported in the literature. Enterotomy with stone extraction alone appears to be associated with better outcomes than more invasive techniques.
Published: 2014

12. Validation of Revised American Joint Committee on Cancer Staging for Gallbladder Cancer Based on a Single Institution Experience

Author: Koh, Christinay, Demirjian, Aram N, Chen, Wen-Pin, Mclaren, Christine E, and Imagawa, David K
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Liver Disease, Digestive Diseases, Patient Safety, Cancer, Clinical Research, Rare Diseases, 6.4 Surgery, Aged, Cholecystectomy, Female, Follow-Up Studies, Gallbladder Neoplasms, Humans, Kaplan-Meier Estimate, Laparoscopy, Male, Neoplasm Staging, Practice Guidelines as Topic, Proportional Hazards Models, Retrospective Studies, Survival Rate, Treatment Outcome, Clinical Sciences, Surgery, Clinical sciences
Abstract: Gallbladder cancer is a rare malignancy, which often goes undiagnosed until advanced stages of disease and is associated with poor prognosis. The only potentially curative treatment is surgical resection. This retrospective study aims to investigate the validity of the revised 7th edition American Joint Committee on Cancer staging criteria and determine prognostic factors. Forty-two patients with confirmed gallbladder cancer who underwent attempted curative resection from 1999 to 2012 at the University of California, Irvine Medical Center were reviewed. Survival probability was determined using the Kaplan-Meier method. Ten patients underwent laparoscopy, were deemed unresectable, and no further surgical intervention was performed. R0 surgical resection, which included radical portal lymphadenectomy, liver segment IVb/V resection, with or without bile duct resection, was performed in the remaining 32 patients. N2 nodes were resected if positive on frozen section. Overall survival probability for Stage I to II patients was 100 per cent. Overall survival probability for Stage III patients was 80 per cent (95% confidence interval [CI], 61 to 99%) and 39.3 per cent (95% CI, 28 to 78%) for Stage IV patients. This study demonstrates that 7th edition clinical stage, T stage, and liver involvement are statistically significant predictors of prognosis. These data also demonstrate a benefit to extended resection in patients even with Stage III and IV disease.
Published: 2013

13. Clinical Presentation of Hepatocellular Carcinoma (HCC) in Asian-Americans Versus Non-Asian-Americans

Author: Wong, Philip Y, Xia, Victor, Imagawa, David K, Hoefs, John, and Hu, Ke-Qin
Subjects: Chronic Liver Disease and Cirrhosis, Rare Diseases, Digestive Diseases, Hepatitis - B, Liver Cancer, Hepatitis, Cancer, Liver Disease, Emerging Infectious Diseases, Infectious Diseases, Clinical Research, Good Health and Well Being, Aged, Asian, California, Carcinoma, Hepatocellular, Female, Humans, Liver Neoplasms, Male, Medical Audit, Middle Aged, Asian-Americans, Ethnicity, Hepatocellular carcinoma, Staging HCC, Cirrhosis, Hepatitis B, Hepatitis C, Public Health and Health Services, Public Health
Abstract: The incidence of HCC is rising worldwide. Studies on ethnicity-based clinical presentation of HCC remain limited. The aim is to compare the clinical presentation and stage of HCC between Asian-Americans and non-Asian-Americans. This retrospective study assessed ethnicity-based differences in HCC presentation, including demographics, laboratory results, diagnosis of underlying liver disease, and stage of HCC. Of 276 patients, 162 were Asian-Americans and 114 were non-Asian-Americans. Compared to non-Asian-Americans, Asian-Americans had a significantly higher incidence of history of hepatitis B virus (HBV) infection (55.0% vs. 4.9%, P
Published: 2011

14. Phase IIA trial testing erlotinib as an intervention against intraductal pancreatic mucinous neoplasms.

Author: Lipkin, Steven, Lee, John, Imagawa, David, Hewitt, Stephen M, Tucker, Chris, Zell, Jason A, Wong, Vanessa, Garcia, Angela, Gonzalez, Rachel, Della Zanna, Gary, Richmond, Ellen, Rodriguez, L M, Bigg, M, Schnoll-Sussmans, F, and Meyskens, Frank
Subjects: Adenocarcinoma, Mucinous: drug therapy, Antineoplastic Agents: pharmacokinetics, therapeutic use, Carcinoma, Pancreatic Ductal: drug therapy, Humans, Male, Middle Aged, Mucin 5AC: biosynthesis, drug effects, Pancreatic Neoplasms: drug therapy, Quinazolines: pharmacokinetics, therapeutic use, erlotinib, mucin 5AC, appetite disorder, article, cancer surgery, diarrhea, drug blood level, drug efficacy, drug safety, drug tolerability, dry skin, endoscopic echography, headache, high performance liquid chromatography, human, immunohistochemistry, insomnia, intraductal papillary mucinous tumor, needle biopsy, outcome assessment, phase 2 clinical trial, priority journal, rash, remission, tandem mass spectrometry, Adenocarcinoma, Mucinous, Antineoplastic Agents, Carcinoma, Pancreatic Ductal, Humans, Male, Middle Aged, Mucin 5AC, Pancreatic Neoplasms, Quinazolines
Abstract: Intraductal papillary mucinous neoplasms (IPMN) are a distinct type of precursor lesions that cause about 5% of pancreatic adenocarcinoma (1, 2). Four-year survival rates of 40% to 75% are reported (3-7). There is currently no chemotherapy specifically approved for treating IPMNs. The number of IPMN cases has significantly increased over the last decade (8).
Published: 2011

15. Adenosquamous Versus Adenocarcinoma of the Pancreas: A Population-Based Outcomes Analysis

Author: Katz, Matthew Harold G, Taylor, Thomas H, Al-Refaie, Waddah B, Hanna, Mark H, Imagawa, David K, Anton-Culver, Hoda, and Zell, Jason A
Subjects: Cancer, Digestive Diseases, Rare Diseases, Pancreatic Cancer, Clinical Research, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Adenocarcinoma, Aged, Carcinoma, Adenosquamous, Female, Humans, Male, Morbidity, Pancreatectomy, Pancreatic Neoplasms, Population Surveillance, Prognosis, Registries, Retrospective Studies, Survival Rate, United States, Pancreatic cancer, Adenosquamous cancer, Pancreaticoduodenectomy, Pancreas, Clinical Sciences, Surgery
Abstract: BackgroundPancreatic adenosquamous carcinoma has historically been characterized as having a more aggressive clinical course than ductal adenocarcinoma. The natural history of this disease, however, is essentially unknown.MethodsWe evaluated the clinical characteristics of all patients with pancreatic adenosquamous carcinoma recorded in the California Cancer Registry 2000-2007 and compared them to those of patients with ductal adenocarcinoma.ResultsNinety-five patients with pancreatic adenosquamous carcinoma and 14,746 patients with ductal adenocarcinoma were identified. Demographics were similar between subtypes (p > 0.05). Disease stage at presentation was also similar; over 50% of each diagnostic group presented with metastatic disease (p = 0.62). Surgical resection was more common among patients with locoregional adenosquamous carcinoma than adenocarcinoma (p = 0.0004), but rates of adjuvant therapy administration were similar (p > 0.05). The cohorts' median overall survival durations were similar in a Cox proportional hazards model (p = 0.45); overall survival was also similar when only patients with resected disease were considered (p = 0.65). Early stage, resection and receipt of radiation or chemotherapy were favorable independent prognostic factors among patients with adenosquamous carcinoma. The median overall survival duration of patients with resected adenosquamous carcinoma was 12 months (95% CI, 8-52).ConclusionsAdenosquamous carcinoma has a natural history similar to that of ductal adenocarcinoma when treated with prevalent clinical patterns of care.
Published: 2011

16. Metronomic gemcitabine in combination with sunitinib inhibits multisite metastasis and increases survival in an orthotopic model of pancreatic cancer.

Author: Tran Cao, Hop S, Bouvet, Michael, Kaushal, Sharmeela, Keleman, Alex, Romney, Eric, Kim, Ginna, Fruehauf, John, Imagawa, David K, Hoffman, Robert M, and Katz, Matthew HG
Subjects: Cell Line, Cell Line, Tumor, Animals, Humans, Mice, Mice, Nude, Pancreatic Neoplasms, Neoplasm Metastasis, Pyrroles, Indoles, Luminescent Proteins, Deoxycytidine, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Tumor Burden, Xenograft Model Antitumor Assays, Inhibitory Concentration 50, Cell Proliferation, Cell Survival, Dose-Response Relationship, Drug, Drug Synergism, Female, Kaplan-Meier Estimate, Sunitinib, Tumor, Nude, Dose-Response Relationship, Drug, Rare Diseases, Cancer, Orphan Drug, Pancreatic Cancer, Digestive Diseases, 5.1 Pharmaceuticals, Oncology & Carcinogenesis, Oncology and Carcinogenesis, Pharmacology and Pharmaceutical Sciences
Abstract: Metronomic chemotherapy suppresses growth of primary tumors and established metastases. However, its effect on metastatic progression is essentially unknown. We report the treatment of a metastatically competent model of pancreatic cancer with metronomic gemcitabine and sunitinib. Mice with orthotopic, red fluorescent protein-expressing, pancreatic cancer tumorgrafts were treated with gemcitabine on a metronomic (1 mg/kg daily, METG) or maximum tolerated dose (150 mg/kg twice weekly, MTDG) schedule with or without sunitinib (SU). Rates of primary tumor growth, metastasis, ascites, and survival were calculated. Gemcitabine at a daily dose of 2 mg or greater led to toxicity within 1 month in mice without tumors but METG at 1 mg/kg/d was well tolerated. Mice with pancreatic cancer tumorgrafts died with metastatic disease at a median of 25 days. METG/SU significantly prolonged median overall survival (44 days) compared with control or either regimen alone (P < 0.05). Primary tumor growth was inhibited by METG/SU (P = 0.03) but neither METG nor sunitinib alone. In contrast, treatment with METG suppressed metastasis at multiple sites, an effect enhanced by sunitinib. MTDG with or without sunitinib had the most favorable effect on primary tumor growth and survival, but its antimetastatic efficacy was similar to that of METG/SU. von Willebrand factor expression was inhibited by METG. Antimetastatic activity approaching that of MTDG is achieved with a total dose reduced 42 times using METG and is further enhanced by sunitinib. Our results suggest the potential of this therapeutic paradigm against pancreatic cancer in the adjuvant and maintenance settings.
Published: 2010

17. Metronomic Gemcitabine in Combination with Sunitinib Inhibits Multisite Metastasis and Increases Survival in an Orthotopic Model of Pancreatic Cancer

Author: Cao, Hop S Tran, Bouvet, Michael, Kaushal, Sharmeela, Keleman, Alex, Romney, Eric, Kim, Ginna, Fruehauf, John, Imagawa, David K, Hoffman, Robert M, and Katz, Matthew HG
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Orphan Drug, Rare Diseases, Cancer, Digestive Diseases, Pancreatic Cancer, 5.1 Pharmaceuticals, Animals, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Cell Line, Cell Line, Tumor, Cell Proliferation, Cell Survival, Deoxycytidine, Dose-Response Relationship, Drug, Drug Synergism, Female, Humans, Indoles, Inhibitory Concentration 50, Kaplan-Meier Estimate, Luminescent Proteins, Mice, Mice, Nude, Neoplasm Metastasis, Pancreatic Neoplasms, Pyrroles, Sunitinib, Tumor Burden, Xenograft Model Antitumor Assays, Gemcitabine, Red Fluorescent Protein, Pharmacology and Pharmaceutical Sciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract: Metronomic chemotherapy suppresses growth of primary tumors and established metastases. However, its effect on metastatic progression is essentially unknown. We report the treatment of a metastatically competent model of pancreatic cancer with metronomic gemcitabine and sunitinib. Mice with orthotopic, red fluorescent protein-expressing, pancreatic cancer tumorgrafts were treated with gemcitabine on a metronomic (1 mg/kg daily, METG) or maximum tolerated dose (150 mg/kg twice weekly, MTDG) schedule with or without sunitinib (SU). Rates of primary tumor growth, metastasis, ascites, and survival were calculated. Gemcitabine at a daily dose of 2 mg or greater led to toxicity within 1 month in mice without tumors but METG at 1 mg/kg/d was well tolerated. Mice with pancreatic cancer tumorgrafts died with metastatic disease at a median of 25 days. METG/SU significantly prolonged median overall survival (44 days) compared with control or either regimen alone (P < 0.05). Primary tumor growth was inhibited by METG/SU (P = 0.03) but neither METG nor sunitinib alone. In contrast, treatment with METG suppressed metastasis at multiple sites, an effect enhanced by sunitinib. MTDG with or without sunitinib had the most favorable effect on primary tumor growth and survival, but its antimetastatic efficacy was similar to that of METG/SU. von Willebrand factor expression was inhibited by METG. Antimetastatic activity approaching that of MTDG is achieved with a total dose reduced 42 times using METG and is further enhanced by sunitinib. Our results suggest the potential of this therapeutic paradigm against pancreatic cancer in the adjuvant and maintenance settings.
Published: 2010

18. Delayed gastric emptying is associated with increased risk of mortality in patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma

Author: Dominguez, Oscar Hernandez, Grigorian, Areg, Wolf, Ronald F, Imagawa, David K, Nahmias, Jeffry T, and Jutric, Zeljka
Subjects: Gastroparesis, Pancreatic cancer, Adenocarcinoma, Pancreaticoduodenectomy, Pancreatic Neoplasms, Pancreatic Fistula, Postoperative Complications, Pancreatectomy, Rare Diseases, Good Health and Well Being, Gastric Emptying, Risk Factors, Clinical Research, Humans, Surgery, Patient Safety, Delayed gastric emptying, Digestive Diseases, Cancer
Abstract: Delayed gastric emptying (DGE) is common in patients undergoing pancreaticoduodenectomy (PD). The effect of DGE on mortality is less clear. We sought to identify predictors of mortality in patients undergoing PD for pancreatic adenocarcinoma hypothesizing DGE to independently increase risk of 30-day mortality. The ACS-NSQIP targeted pancreatectomy database (2014–2017) was queried for patients with pancreatic adenocarcinoma undergoing PD. A multivariable logistic regression analysis was performed. Separate sensitivity analyses were performed adjusting for postoperative pancreatic fistula (POPF) grades A–C. Out of 8011 patients undergoing PD, 1246 had DGE (15.6%). About 8.5% of patients with DGE had no oral intake by postoperative day-14. The DGE group had a longer median operative duration (373 vs. 362 min, p = 0.019), and a longer hospital length of stay (16.5 vs. 8 days, p p p
Published: 2022
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19. Postoperative Anticoagulation in Vascular Reconstructions Associated with Malignancies

Author: Mariana, Krutman, Kenji, Nishinari, Bruno Soriano, Pignataro, Rafael Noronha, Cavalcante, Igor Yoshio Imagawa, Fonseca, Guilherme, Centofanti, Nicole, Inforsato, and Guilherme, Yazbek
Subjects: Blood Vessel Prosthesis Implantation, Treatment Outcome, Neoplasms, Humans, Anticoagulants, Surgery, General Medicine, Cardiology and Cardiovascular Medicine, Vascular Patency, Retrospective Studies
Abstract: The invasion of truncal arteries and veins by malignant neoplasms is rare and the surgical treatment remains a challenge. Several techniques can be used to re-establish blood flow in a resected vessel and choice of the ideal vascular substitute frequently arises a debate. Comparative studies between prosthetic and autologous grafts disclose conflicting patency results. The aim of this study is to compare patency outcomes of vascular reconstructions performed using autologous or prosthetic replacement grafts in surgical oncology, in light of a standardized antithrombotic protocol used in our institution since 1997.This retrospective study compared patency of prosthetic versus autologous interposition grafts following the resection of malignancies in 117 patients between September 1997 and February 2020. The 181 reconstruction procedures performed were analyzed according to the body segment involved, and divided into: head and neck, thorax, abdomen, and extremities.Overall survival estimates after 24 and 60 months were 53.2% (standard error 4.8%) and 38.1% (standard error 4.9%), respectively. No significant difference was observed between overall arterial patency, using autologous or synthetic grafts (P = 0.41). Overall venous patency showed a tendency to be lower in synthetic grafts, although no significant difference was observed (P = 0.062). For both arterial and venous reconstructions in the extremities (upper and lower limbs), significantly higher patency was observed using autologous grafts.Autologous long-term graft patency may be superior to prosthetic in vascular reconstructions associated with malignancies of the extremities. This outcome was obtained using a standardized post-operative anticoagulation protocol.
Published: 2022
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20. Mechanism of crescent-shaped and ring-shaped epidermal damage from laser hair removal with cryogen spray cooling

Author: Kotaro Imagawa, Taro Kono, Chieko Komaba, Satoru Yamamoto, Yotaro Tsunoda, Hitoshi Nemoto, Ushio Hanai, William F. Groff, and Tadashi Akamatsu
Subjects: Hyperpigmentation, Lasers, Humans, Surgery, Laser Therapy, Dermatology, Epidermis, Hair Removal, Skin Temperature, Skin
Abstract: The safety and efficacy of laser hair removal have been well established through many clinical studies and through clinical use over the past 25 years. A laser hair removal device that protects the epidermis by utilizing cryogen spray cooling (CSC) is widely used internationally. In darker skin types, post-inflammatory hyperpigmentation (PIH) can occur after laser hair removal. In particular, laser hair removal with CSC is known to cause crescent-shaped or ring-shaped PIH. In this experiment, we report a visualization of this PIH mechanism. The laser used in this experiment is a 755-nm-long-pulsed alexandrite laser. Graph paper was treated with this laser to assess for thermal damage. We investigated changes in thermal damage due to differences in laser spot size, fluence output, and laser beam angle in relation to the graph paper. When using a spot size of 18 mm, we observed that higher fluences caused crescent-shaped thermal damage on the margins of the treated graph paper. It was also confirmed that when the hand piece is not held perpendicular to the skin, the laser-treated area is expanded and the CSC range is narrowed. These factors caused the area of thermal damage to widen. This widening causes ring-shaped thermal injury, leading to PIH. We treated graph paper using a hair removal laser with CSC to investigate the mechanism of crescent or ring-shaped thermal damage. Laser treatment on graph paper is effective as a test for defects in the CSC device. Factors that cause inadequate cooling, which leads to PIH, are large spot size, high fluence, not holding the laser hand piece perpendicular to the skin, and malfunctioning of CSC device.
Published: 2022
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21. Perillyl Alcohol Inhibits TCR-Mediated [Ca2+]i Signaling, Alters Cell Shape and Motility, and Induces Apoptosis in T Lymphocytes

Author: Wei, Xunbin, Si, Ming-Sing, Imagawa, David K, Ji, Ping, Tromberg, Bruce J, and Cahalan, Michael D
Subjects: Biomedical and Clinical Sciences, Immunology, Alcoholism, Alcohol Use and Health, Substance Misuse, Prevention, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Adult, Alkyl and Aryl Transferases, Animals, Apoptosis, Calcium, Cell Movement, Cell Polarity, Cell Size, Enzyme Inhibitors, Humans, Mice, Monoterpenes, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, Terpenes
Abstract: Perillyl alcohol (POH) inhibits isoprenylation and has shown anticancer and chemopreventive properties in rodent models. The mechanism that underlies the anticancer activity of POH and other isoprenylation inhibitors is unknown but has been postulated to involve decreased levels of isoprenylated Ras and Ras-related proteins. Previously we demonstrated that POH effectively inhibits human T cell proliferation in vitro and can prevent acute and chronic rejection in a rat cardiac transplant model. In this report, we investigate the effects of POH on T lymphocytes at the single-cell level. POH disrupts the polarized shape and motility of antigen-specific murine 1E5 T cells. Using an optical trap to position anti-CD3-coated beads in contact with 1E5 T cells, we demonstrate that POH inhibits their TCR-mediated calcium response. Furthermore, we show that POH preferentially induces apoptosis in PHA-activated human T cells as well as in 1E5 T cells.
Published: 2000

22. De novo non-synonymous CTR9 variants are associated with motor delay and macrocephaly: human genetic and zebrafish experimental evidence

Author: Hisato Suzuki, Kana Aoki, Kenji Kurosawa, Kazuo Imagawa, Tatsuyuki Ohto, Mamiko Yamada, Toshiki Takenouchi, Kenjiro Kosaki, and Tohru Ishitani
Subjects: Mammals, Nuclear Proteins, Human Genetics, General Medicine, Phosphoproteins, Megalencephaly, Intellectual Disability, Genetics, Animals, Humans, Mutant Proteins, Molecular Biology, Zebrafish, Genetics (clinical), Transcription Factors
Abstract: CTR9 is one of five genes that form the PAF1 complex, which binds to RNA polymerase II and plays critical roles in transcriptional elongation and transcription-coupled histone modifications including histones H3K4me3 and H3K36me3. In this study, de novo CTR9 non-synonymous variants (p.(Glu15Asp) and p.(Pro25Arg)) were detected in two unrelated patients with macrocephaly, motor delay, and intellectual disability. A pull-down assay showed that the mutant CTR9 proteins had stronger affinities to the PAF1 protein than the wild-type protein. Functional analyses using zebrafish showed that the knockout of the ctr9 gene caused motor defects and enlargement of the telencephalon, which is homologous to the mammalian cerebrum. The rescue experiment, in which the human CTR9 mutants were introduced into ctr9-knockout zebrafish, failed to maintain the swimming posture of the ctr9-knockout fish, suggesting that the human CTR9 mutant proteins do not function normally in vivo. In addition, the overexpression of human CTR9 mutant mRNA caused telencephalon enlargement in zebrafish larvae, suggesting that the human CTR9 mutant proteins interfered with normal endogenous CTR9 function. We concluded that the two missense variants in CTR9 (p.(Glu15Asp) and p.(Pro25Arg)) cause a new syndrome involving macrocephaly, motor delay and intellectual disability through the loss of the normal function of CTR9 and the inhibition of the normal intrinsic CTR9 function of the contralateral allele.
Published: 2022
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23. The impact of sarcopenia on low back pain and quality of life in patients with osteoporosis

Author: Shoji Iwahashi, Ryuki Hashida, Hiroo Matsuse, Eriko Higashi, Masafumi Bekki, Sohei Iwanaga, Koji Hara, Takahiko Higuchi, Yohei Hirakawa, Asami Kubota, Hiromi Imagawa, Yoko Muta, Kazuhito Minamitani, Tatsuhiro Yoshida, Kimiaki Yokosuka, Kei Yamada, Kimiaki Sato, and Naoto Shiba
Subjects: Adult, Quality of life, Adults spinal deformity, Sarcopenia, Diseases of the musculoskeletal system, musculoskeletal system, body regions, Cross-Sectional Studies, Sagittal alignments, Rheumatology, RC925-935, Humans, Osteoporosis, Orthopedics and Sports Medicine, Low Back Pain, human activities
Abstract: Purpose Osteoporosis combined with sarcopenia contributes to a high risk of falling, fracture, and even mortality. However, sarcopenia’s impact on low back pain and quality of life (QOL) in patients with osteoporosis is still unknown. The purpose of this study is to investigate low back pain and QOL in osteoporosis patients with sarcopenia. Methods We assessed 100 ambulatory patients who came to our hospital for osteoporosis treatment. Low back pain was evaluated using the Visual Analogue Scale (VAS) with 100 being an extreme amount of pain and 0 no pain. The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) score was used to assess QOL after adjustment for age, history of vertebral fracture, and adult spinal deformity. Differences in low back pain intensity assessed by VAS between groups were evaluated by the Willcoxon rank-sum test. Covariance analysis was used to assess QOL. All data are expressed as either median, interquartile range, or average, standard error. Results Patients were classified into the sarcopenia group (n = 32) and the non-sarcopenia group (n = 68). Low back pain intensity assessed by VAS was significantly higher in the sarcopenia group than in the non-sarcopenia group (33.0 [0-46.6] vs. 8.5 [0-40.0]; p p Conclusion In this cross-sectional study, sarcopenia affected low back pain and QOL in ambulatory patients with osteoporosis. Sarcopenia may exacerbate low back pain and QOL.
Published: 2022

24. Expression of Karyopherin Alpha 2 and Karyopherin Beta 1 Correlate with Poor Prognosis in Gastric Cancer

Author: Yoshihito Ohhara, Ichiro Kinoshita, Akira Suzuki, Makoto Imagawa, Jun Taguchi, Takuro Noguchi, Satoshi Takeuchi, Yasushi Shimizu, Hideyuki Seki, Junichi Suzuki, and Hirotoshi Dosaka-Akita
Subjects: alpha Karyopherins, Cancer Research, Oncology, Stomach Neoplasms, Humans, General Medicine, beta Karyopherins, Prognosis
Abstract: Introduction: Karyopherin alpha 2 (KPNA2) and karyopherin beta 1 (KPNB1) constitute nuclear transport protein complexes involved in nuclear import and are significant in tumor progression. Although high KPNA2 expression was associated with poor prognosis in solid tumors, the relationship between KPNA2 and KPNB1 expression and their prognostic role in gastric cancer (GC) remains unclear. Methods: Immunohistochemistry was used to correlate the expression of KPNA2 and KPNB1 with various features, including clinicopathological characteristics in 130 patients with GC and survival in 94 patients with invasive lesions extending to the submucosa or deeper. Results: High expression of KPNA2 and KPNB1 was found in 25% and 36% of the patients, respectively. Both were significantly related to tumor depth, lymph node metastasis, lymphatic invasion, venous invasion, and Ki-67 expression. KPNA2 expression was significantly related to that of KPNB1 (p < 0.001). Patients with high KPNB1 expression had poorer prognosis than those with low expression (p = 0.027), as was also observed in case of KPNA2 (p < 0.001). Patients with high expression of both KPNA2 and KPNB1 accounted for 18% and had a poorer prognosis than those with high expression of either and those with low expression of both (p = 0.001). Multivariate analysis revealed that high expression of both KPNA2 and KPNB1 was an independent prognostic factor in patients with GC (hazard ratio, 3.46; 95% confidence interval, 1.64–2.73, p = 0.001). Conclusion: KPNA2 expression was correlated with KPNB1 expression, and high co-expression of KPNA2 and KPNB1 may represent a strong prognostic biomarker in GC.
Published: 2022
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25. Comparison Between Second- and Third-generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors as First-line Treatment in Patients With Non-small-cell Lung Cancer: A Retrospective Analysis

Author: Takahiko Nakamura, Kenjiro Tsuruoka, Kiyoe Kanaoka, Yosuke Tamura, Yasuhito Fujisaka, Soichiro Ikeda, Tomoya Funamoto, Masafumi Imanishi, Isao Goto, Akihisa Imagawa, Hiroyuki Tsuji, Sho Mitsuya, and Ninso Matsunaga
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Afatinib, T790M, Carcinoma, Non-Small-Cell Lung, Internal medicine, medicine, Humans, Osimertinib, Epidermal growth factor receptor, Lung cancer, Protein Kinase Inhibitors, Aged, Retrospective Studies, Aged, 80 and over, Acrylamides, Aniline Compounds, biology, business.industry, Hazard ratio, General Medicine, Middle Aged, Prognosis, medicine.disease, Confidence interval, respiratory tract diseases, ErbB Receptors, Survival Rate, Mutation, biology.protein, Female, Non small cell, business, Follow-Up Studies, medicine.drug
Abstract: BACKGROUND For epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), administration of EGFR tyrosine kinase inhibitors (TKIs) is mandatory to prolong survival. To date, a comparison of second- and third-generation EGFR-TKIs has not been reported as far as we are aware. PATIENTS AND METHODS We retrospectively investigated the survival time of patients diagnosed with EGFR-mutated advanced or recurrent NSCLC who had received afatinib, a second-generation EGFR-TKI, or osimertinib, a third-generation EGFR-TKI, as the first-line treatment. RESULTS Among the 49 patients included in the study, 15 received afatinib and 34 received osimertinib. No significant differences in overall survival were observed between the two groups [afatinib vs. osimertinib=36 vs. 33 months (hazard ratio=2.917, 95% confidence interval=0.780-10.905; p=0.112)]. T790M mutation was detected in three of the patients in the afatinib group, and all three subsequently received osimertinib. The median overall survival of these three patients and of the 12 without the mutation were 63 and 36 months, respectively. CONCLUSION There was no apparent difference in the effect on survival between second- and third-generation EGFR-TKIs, whereas the sequential administration of second- followed by third-generation EGFR-TKIs appeared to confer a better long-term prognosis.
Published: 2021
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26. Kawasaki disease with dilatation of the common bile duct: A case report and review of literature

Author: Hidetoshi Takada, Takumi Ishiodori, Atsushi Morita, Kazuo Imagawa, and Manabu Tagawa
Subjects: Male, medicine.medical_specialty, Heart disease, Prednisolone, Mucocutaneous Lymph Node Syndrome, Gastroenterology, Rheumatology, Predictive Value of Tests, Cervical lymphadenopathy, Internal medicine, medicine, Humans, Glucocorticoids, Ultrasonography, Common Bile Duct, Common bile duct, business.industry, Immunoglobulins, Intravenous, Echogenicity, medicine.disease, Treatment Outcome, medicine.anatomical_structure, Child, Preschool, Cholecystitis, Kawasaki disease, medicine.symptom, business, Dilatation, Pathologic, medicine.drug, Systemic vasculitis
Abstract: Background Kawasaki disease (KD), which was first described by Tomisaku Kawasaki in 1967, is a syndrome that results in acute systemic vasculitis, affecting mainly infants and children, and is a major cause of acquired heart disease in developed countries. KD is diagnosed based on certain characteristic symptoms and echocardiogram results. It has been reported that neck and abdominal ultrasound is also reliable diagnostic method. Nevertheless, abdominal ultrasound is not a routine procedure in KD. Moreover, dilatation of the common bile duct (CBD) has been rarely reported in previous cases. Case presentation: A 4-year-old boy presented with fever and markedly high transaminase level (AST, 5,323 U/L, ALT, 1,554 U/L). The patient was diagnosed as having KD based on characteristic symptoms and echocardiogram findings. Neck and abdominal ultrasound revealed dilatation of the CBD as well as cervical lymphadenopathy resembling a cluster of grapes, thickening of the gallbladder wall, and increased periportal echogenicity throughout the liver parenchyma. The patient received initial treatment with intravenous immunoglobulin (IVIG) at day 4 of fever, following which, transaminase level decreased. The patient received second-line treatment with IVIG and prednisolone because of recurrent fever on day 6. Dilatation of the CBD was improved from 6.6 mm on day 4 to 3.1 mm on day 8. Although re-dilatation was observed, it gradually diminished and normalized (4.3 mm on day 28, 4.0 mm on day 63, 3.3 mm on day 105, and 2.8 mm on day 182). Conclusion This case highlights the usefulness of abdominal ultrasound and the importance of considering dilatation of the CBD as one of the complications of KD. Because abdominal ultrasound is not a routine procedure in KD, it is possible that dilatation of the CBD in KD is quite latent if not investigated thoroughly. Further prospective studies to support these findings are warranted.
Published: 2021
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27. Research following genome‐wide association study focuses on the multifaceted nature of Src kinase‐associated phosphoprotein 2 in type 1 diabetes

Author: Hiroyuki Sano and Akihisa Imagawa
Subjects: Diabetes Mellitus, Type 1, src-Family Kinases, Macrophages, Endocrinology, Diabetes and Metabolism, Internal Medicine, Humans, General Medicine, Phosphoproteins, Genome-Wide Association Study
Abstract: Rutsch et al. identified a patient with type 1 diabetes having a rare Src kinase-associated phosphoprotein 2 variant and investigated the details. As a result, they showed that rare Src kinase-associated phosphoprotein 2 c.475 GA increases macrophage activity and promotes type 1 diabetes, as well as autoimmune and inflammatory diseases.
Published: 2022
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28. A prospective multicenter study of the magnifying endoscopic evaluation of the invasion depth of superficial esophageal cancers

Author: Masahiro Nakagawa, Yoshiyasu Kono, Yoshiro Kawahara, Shuhei Ishiyama, Hiroyuki Okada, Sayo Kobayashi, Masaya Iwamuro, Keisuke Hori, Makoto Abe, Seiji Kawano, Tatsuhiro Gotoda, Tatsuya Toyokawa, Atsushi Imagawa, and Hiromitsu Kanzaki
Subjects: Invasion depth, medicine.medical_specialty, Esophageal Neoplasms, business.industry, Diagnostic accuracy, Hepatology, Predictive value, Narrow Band Imaging, Multicenter study, Internal medicine, Carcinoma, Squamous Cell, medicine, Retrospective analysis, Humans, Treatment strategy, Neoplasm Invasiveness, Surgery, Esophageal Squamous Cell Carcinoma, Esophagoscopy, Prospective Studies, Radiology, business, Retrospective Studies, Abdominal surgery
Abstract: Treatment strategies for superficial esophageal squamous cell carcinoma (SESCC) are determined mainly on the basis of the invasion depth. The Japan Esophageal Society (JES) developed a simplified magnifying endoscopic classification for estimating the invasion depth of SESCC. We aimed to evaluate its accuracy. We prospectively applied the JES classification for estimating the invasion depth of SESCC to 204 consecutive lesions from 6 hospitals in Japan between April 2016 and October 2018. We analyzed the accuracy of the endoscopic diagnosis by adding the following two categories to the JES classification: ≥ 7 mm lesion in B2 vessels (defined as B2 ≥ 7 mm) and B2 vessels with inflammation (defined as B2i). After applying the exclusion criteria, 201 lesions remained in the analysis. The diagnostic value of type B1, B2, B3 vessels were as follows: sensitivity, 93.9%, 68.0%, 25.0%; specificity, 81.1%, 89.2%, 99.4%; positive predictive value (PPV), 95.6%, 47.2%, 75.0%; negative predictive value (NPV), 75.0%, 95.1%, 95.4%; and accuracy, 91.5%, 86.5%, 95.0%, respectively. A retrospective analysis showed that the diagnostic accuracy was higher in type B2 vessels (86.5% to 92.0%). An avascular area (AVA) was found in 55 (27%) of the 201 lesions, which tended to be associated with a deeper pathological diagnosis of each Type B vessel. In an additional analysis, B2 ≥ 7 mm and B2i improved the diagnostic accuracy of type B2 vessels from 86.5% to 92.0%. The JES classification is useful for estimating the invasion depth of SESCC. The diagnostic accuracy for type B2 vessels was low, which may be improved by using B2 ≥ 7 mm and B2i.
Published: 2021
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29. Characterization of salivary microbiota in elderly patients with type 2 diabetes mellitus: a matched case–control study

Author: Takaaki Ueno, Kuniyasu Kamiya, Shoichi Sakaguchi, Michi Omori, Nahoko Kato-Kogoe, Shota Nakamura, Chee Hoe Kit, Yan-Hong Gu, Nozomu Fukui, Junko Tamaki, Akihisa Imagawa, Takashi Nakano, and Masaaki Hoshiga
Subjects: medicine.medical_specialty, Saliva, endocrine system diseases, Phylum Firmicutes, 03 medical and health sciences, Oral Microbiota, 0302 clinical medicine, RNA, Ribosomal, 16S, Internal medicine, Humans, Medicine, In patient, General Dentistry, Aged, business.industry, Microbiota, Case-control study, Area under the curve, nutritional and metabolic diseases, Type 2 Diabetes Mellitus, 030206 dentistry, stomatognathic diseases, UniFrac, Diabetes Mellitus, Type 2, Case-Control Studies, 030220 oncology & carcinogenesis, business
Abstract: The importance of oral health in type 2 diabetes mellitus (T2DM) is widely recognized; however, oral microbiota characteristics associated with T2DM in the elderly population are not well-understood. This study was conducted to evaluate the characteristics of the salivary microbiota in elderly Japanese patients with T2DM. Saliva samples were collected from 42 elderly Japanese patients with T2DM and 42 age- and sex-matched subjects without T2DM (control). 16S ribosomal RNA metagenomic analysis and comparative analysis of both groups were performed. Random forest classification by machine learning was performed to discriminate between the salivary microbiota in the two groups. There were significant differences in the overall salivary microbiota structure between the T2DM and control groups (beta diversity; unweighted UniFrac distances, p = 0.001; weighted UniFrac distances, p = 0.001). The phylum Firmicutes was abundant in patients with T2DM, whereas the phylum Bacteroidetes was abundant in controls. The T2DM prediction model by random forest based on salivary microbiota data was verified with a high predictive potential in five cross-validation tests (area under the curve (AUC) = 0.938 (95% CI, 0.824–1.000)). Characterization revealed that the salivary microbiota profile of the elderly patients with T2DM is significantly distinct from that of the controls. These data indicate the necessity of oral health management based on the characteristics of the salivary microbiota in elderly patients with T2DM. Our findings will contribute to future research on the development of new diagnostic and therapeutic methods for this purpose.
Published: 2021
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30. Pediatric cardiac tamponade caused by metallic wire penetration into the heart: A case report and literature review

Author: Hajime Yamazaki, Muneaki Matsubara, Hideyuki Kato, Kazuo Imagawa, Takashi Murakami, Bryan J. Mathis, and Yuji Hiramatsu
Subjects: Pulmonary and Respiratory Medicine, Foreign-Body Migration, Heart Ventricles, Humans, Surgery, Child, Foreign Bodies, Cardiology and Cardiovascular Medicine, Cardiac Tamponade
Abstract: Thin, metallic wires can easily penetrate the gastrointestinal system if ingested and cause serious cardiac issues in children. We report a pediatric case of such an object that caused cardiac tamponade after lodging in the left ventricle. The wire was extracted without cardiopulmonary bypass and a full recovery was made. Cardiac issues after ingestion of foreign objects are rare but immediate surgery is required for resolution.
Published: 2022
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31. Safety and tolerability of IgPro10 in Japanese primary immunodeficiency patients: a registrational study

Author: Kimio Morita, Tomohiro Morio, Kozo Yasui, Amgad Shebl, Kenji Gotoh, Hidenori Ohnishi, Jutta Hofmann, John-Philip Lawo, Mikhail Rojavin, and Tomoyuki Imagawa
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Primary Immunodeficiency Diseases, Body weight, 03 medical and health sciences, 0302 clinical medicine, Asian People, Japan, Internal medicine, medicine, Humans, Prospective Studies, Registries, Dosing, Adverse effect, Infusion time, business.industry, Hematology, Middle Aged, medicine.disease, Tolerability, Immunoglobulin G, 030220 oncology & carcinogenesis, Primary immunodeficiency, Female, business, 030215 immunology
Abstract: Studies investigating the safety of IgPro10 (Privigen®, CSL Behring, King of Prussia, PA, USA) in Japanese patients with primary immunodeficiency (PID) are lacking. This study evaluated safety and tolerability of IgPro10 in Japanese patients with PID. In this prospective, open-label, single-arm, registrational study for Japan, IgPro10 was administered intravenously at pre-study doses of 138–556 mg/kg body weight per 3-/4-weekly dosing cycle for up to 4 months. Frequency and intensity of adverse events (AEs), their relationship to IgPro10 and AE rate per infusion (AERI) were evaluated. Of 11 enrolled patients, 10 completed the study. The median (range) total duration of exposure was 16.14 (4.1–16.3) weeks. Eight patients reported 19 AEs, none severe (based on maximum severity), giving an AERI of 0.442. One AE was deemed related to IgPro10 treatment. Three patients experienced temporally associated AEs. No serious AEs or deaths were reported. Nine patients (90%) who completed the study tolerated flow rates of ≥ 8 mg/kg/min; 5 tolerated 12 mg/kg/min (7.2 mL/kg/h), translating into a threefold decrease in mean infusion time. IgPro10 was well tolerated at a flow rate of up to 12 mg/kg/min. Safety and tolerability findings were consistent with previously reported studies in non-Japanese patients with PID.
Published: 2021
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32. The potential of a universal influenza virus-like particle vaccine expressing a chimeric cytokine

Author: Kuniaki Nerome, Toshifumi Imagawa, Shigeo Sugita, Youta Arasaki, Kenichi Maegawa, Kazunori Kawasaki, Tsuyoshi Tanaka, Shinji Watanabe, Hidekazu Nishimura, Tetsuro Suzuki, Kazumichi Kuroda, Isao Kosugi, and Zenta Kajiura
Subjects: Mice, Inbred BALB C, Ecology, Health, Toxicology and Mutagenesis, Plant Science, Antibodies, Viral, Biochemistry, Genetics and Molecular Biology (miscellaneous), Mice, Hemagglutinins, Orthomyxoviridae Infections, Influenza Vaccines, Influenza, Human, Animals, Humans, Cytokines, Vaccines, Virus-Like Particle
Abstract: The efficacy of the current influenza vaccines is frequently reduced because of antigenic drift, a trade-off of developing improved vaccines with broad cross-protective activity against influenza A viruses. In this study, we have successfully constructed a chimeric cytokine (CC) comprising the M2 protein, influenza A neuraminidase stalk, and interleukin-12. We produced virus-like particles (VLPs) containing CC and influenza hemagglutinin (HA) proteins using a baculovirus system in Eri silkworm pupae. The protective efficacy of the CCHA-VLP vaccine was evaluated in mice. The CCFkH5HA-VLP vaccine increased the survival rates of BALB/c mice, infected with a lethal dose of PRH1 and HKH5 viruses, to 80% and 100%, respectively. The results suggested that CCHA-VLP successfully induced potent cross-reactive protective immunity against infection with homologous and heterologous subtypes of the influenza A virus. This is the first study to design a CC-containing HA-VLP vaccine and validate its protective efficacy.
Published: 2022

33. Tumor Growth Suppression With Novel Intra-arterial Chemotherapy Using Epirubicin-entrapped Water-in-oil-in-water Emulsion In Vivo

Author: Ryouji Mizumachi, Yuuya Ono, Tomoyuki Hisa, Yoshitaka Furuya, Novriana Dewi, Hiroyuki Takahashi, Jun Nakajima, Tadao Nakashima, Masashi Nagata, Minoru Ono, Yasumasa Nonaka, Toshimitsu Terao, Yasuyuki Morishita, Takashi Fujino, Masashi Yanagawa, Koji Seguchi, Mitsuteru Fujihara, Masazumi Eriguchi, Kazuhiko Arimori, Kazuhiro Kakimi, Takeshi Nagasaki, Takumichi Sugihara, Hironobu Yanagie, Shushi Higashi, Yuuji Murata, Ichiro Ikushima, and Takashi Imagawa
Subjects: Cancer Research, Carcinoma, Hepatocellular, food.ingredient, medicine.medical_treatment, Pharmacology, Poppy seed, Endocytosis, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, food, In vivo, medicine, Animals, Humans, Epirubicin, Chemotherapy, Chemistry, Liver Neoplasms, Water, medicine.disease, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cancer cell, Toxicity, Emulsions, Rabbits, Research Article, medicine.drug
Abstract: Background/aim A mixture of anticancer agents and iodized poppy seed oil (IPSO) has been widely used for intra-arterial chemotherapy of hepatocellular carcinoma. However, the anticancer agents can easily separate from IPSO, so the therapeutic potential is limited. We developed epirubicin-entrapped water-in-oil-in-water emulsion (WOW-Epi) using a double-membrane emulsification technique. Materials and methods We delivered WOW-Epi through a hepatic arterial injection to VX2 hepatic tumor rabbit model (1.2 mg/kg). Results VX2 tumor growth was selectively suppressed in the WOW-Epi-treated group compared with the control treated groups. The accumulation of WOW in nearby cancer cells was confirmed via electron-microscopy. Endocytosis seemed to be the mechanism underlying the uptake of WOW. Conclusion WOW-Epi led to tumour growth suppression in vivo. WOW does not cause toxicity to arterial vessels. WOW-Epi will be hopefully used for repeated intra-arterial chemotherapy to HCC patients in the near future.
Published: 2021
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34. Exacerbation of autoimmune myocarditis by an immune checkpoint inhibitor is dependent on its time of administration in mice

Author: Hirofumi Morihara, Kenjiro Tsuruoka, Shigeo Wakabayashi, Ninso Matsunaga, Michio Asahi, Akihisa Imagawa, Yasuhito Fujisaka, and Isao Goto
Subjects: Myocarditis, Autoimmunity, 030204 cardiovascular system & hematology, medicine.disease_cause, Autoimmune Diseases, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Animals, Humans, 030212 general & internal medicine, Interleukin 6, Immune Checkpoint Inhibitors, Mice, Inbred BALB C, biology, Cluster of differentiation, business.industry, medicine.disease, Disease Models, Animal, Collagen, type I, alpha 1, Immunology, biology.protein, Antibody, Cardiology and Cardiovascular Medicine, business, Cardiac Myosins, Infiltration (medical)
Abstract: Background Although immune checkpoint inhibitors (ICIs) have made an immense breakthrough in cancer therapeutics, they can exert unique, immune-related adverse events. Among them, myocarditis is less frequent, but it is serious and often follows a lethal course. Methods To examine the changes in cardiac autoimmunity after ICI administration, we developed a mouse experimental autoimmune myocarditis (EAM) model via intraperitoneal administration of murine α-cardiac myosin heavy chain (MyHC-α) fragment. Thereafter, the mouse anti-PD-1 antibody (mPD1ab) was administered at two time points, subsequent to and concurrent with MyHC-α fragment administration. Results Severe EAM developed in 3 weeks; wide inflammatory lesions were observed in the cardiac sections. Furthermore, inflammatory/fibrotic genes, such as interleukin 1β, interleukin 6, and collagen 1, were upregulated, although the cardiac function was not significantly affected. The subsequent administration of mPD1ab at 2 weeks post administration of the first MyHC-α fragment exacerbated EAM, whereas the administration of mPD1ab concurrent with MyHC-α fragment administration did not exacerbate EAM. The subsequent administration of mPD1ab significantly increased the infiltration of cluster of differentiation (CD)4- and F4/80-positive cells, whereas the concurrent administration of mPD1ab significantly decreased the infiltration of CD4-positive cells, indicating that the concurrent and subsequent administration of mPD1ab had opposite effects on immune/inflammatory cell infiltration. Conclusions These data suggest that the appearance of ICI-induced autoimmune myocarditis might be related to autoimmune system activity before ICI administration. Although ICIs do not adversely affect patients with normal immune systems, we propose that ICI administration should be avoided in patients with autoimmune disorders.
Published: 2020
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35. Distinct Phenotypes of Islet Antigen-Specific CD4+ T Cells Among the 3 Subtypes of Type 1 Diabetes

Author: Chiharu Tsutsumi, Masayuki Shimoda, Kunimasa Yagi, Maya Matsushita, Kohjiro Ueki, Nobuyuki Takahashi, Kazuyuki Tobe, Akihisa Imagawa, Toshiaki Hanafusa, Daisuke Chujo, Fumitaka Haseda, Hiroshi Kajio, and Akitsu Kawabe
Subjects: CD4-Positive T-Lymphocytes, Male, 0301 basic medicine, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, medicine.disease_cause, Autoantigens, Severity of Illness Index, Biochemistry, Autoimmunity, 0302 clinical medicine, Endocrinology, Insulin, Age of Onset, HLA-DR Serological Subtypes, Immunoassay, Immunity, Cellular, geography.geographical_feature_category, Glutamate Decarboxylase, Middle Aged, Islet, Up-Regulation, Cytokine, Disease Progression, Female, Adult, Preproinsulin, medicine.medical_specialty, Adolescent, 030209 endocrinology & metabolism, Biology, Peripheral blood mononuclear cell, Islets of Langerhans, Young Adult, 03 medical and health sciences, Immune system, Antigen, Internal medicine, medicine, Humans, Protein Precursors, Aged, geography, Interleukin-6, Biochemistry (medical), Molecular biology, Chemokine CXCL10, Diabetes Mellitus, Type 1, 030104 developmental biology, Ex vivo
Abstract: Context Type 1 diabetes (T1D) is classified into 3 subtypes: acute-onset (AT1D), slowly progressive (SP1D), and fulminant (FT1D). The differences in the type of cellular autoimmunity within each subtype remain largely undetermined. Objective To determine the type and frequency of islet antigen-specific CD4+ T cells in each subtype of T1D. Participants Twenty patients with AT1D, 17 with SP1D, 18 with FT1D, and 17 persons without diabetes (ND). Methods We performed an integrated assay to determine cellular immune responses and T-cell repertoires specific for islet antigens. This assay included an ex vivo assay involving a 48-hour stimulation of peripheral blood mononuclear cells with antigen peptides and an expansion assay involving intracytoplasmic cytokine analysis. Results The results of the ex vivo assay indicated that glutamic acid decarboxylase 65 (GAD65)-specific interleukin-6 and interferon-inducible protein-10 (IP-10) responses and preproinsulin (PPI)-specific IP-10 responses were significantly upregulated in AT1D compared with those of ND. Furthermore, GAD65- and PPI-specific granulocyte colony-stimulating factor responses were significantly upregulated in FT1D. Expansion assay revealed that GAD65- and PPI-specific CD4+ T cells were skewed toward a type 1 helper T (Th1)- cell phenotype in AT1D, whereas GAD65-specific Th2 cells were prevalent in SP1D. GAD65-specific Th1 cells were more abundant in SP1D with human leukocyte antigen-DR9 than in SP1D without DR9. FT1D displayed significantly less type 1 regulatory T (Tr1) cells specific for all 4 antigens than ND. Conclusions The phenotypes of islet antigen-specific CD4+ T cells differed among the three T1D subtypes. These distinct T-cell phenotypes may be associated with the manner of progressive β-cell destruction.
Published: 2020
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36. Lagophthalmos after congenital ptosis surgery: comparison between maximal levator resection and frontalis sling operation

Author: Jaeho Jang, Stephanie M. Young, Ji Woong Park, Kyung In Woo, Yoon-Duck Kim, and Yukihiro Imagawa
Subjects: Blepharoplasty, medicine.medical_specialty, Sling (implant), Lagophthalmos, Levator resection, Article, 03 medical and health sciences, 0302 clinical medicine, Fascia lata, Superficial punctate keratopathy, medicine, Blepharoptosis, Humans, Outpatient clinic, Retrospective Studies, business.industry, Levator function, medicine.disease, Surgery, Ophthalmology, Cross-Sectional Studies, Treatment Outcome, medicine.anatomical_structure, Oculomotor Muscles, 030221 ophthalmology & optometry, Congenital ptosis, business, 030217 neurology & neurosurgery
Abstract: Background/objectives To compare postoperative lagophthalmos after maximal levator resection (MLR) and frontalis suspension (FS) in congenital ptosis patients with poor levator function (LF). Methods A cross-sectional study was performed to compare postoperative outcomes in patients with preoperative LF ≤ 4 mm who had undergone MLR or FS at a single tertiary institution, and who had visited the outpatient clinic between February 2017 and August 2018. Main outcome measures were as follows: (1) Preoperative LF and margin reflex distance 1 (MRD1), (2) Postoperative MRD1, lagophthalmos and grade of superficial punctate keratopathy (SPK). Results Our study comprised 152 eyelids of 122 patients. There were 71 eyelids in the MLR group and 81 eyelids in the FS group. The MLR group had comparable mean postoperative MRD1 (2.8 ± 0.8 mm) to the FS with autogenous fascia lata (AFL) group (3.0 ± 0.7 mm), while the FS with preserved fascia lata (PFL) group had the lowest mean postoperative MRD1 (2.2 ± 1.0 mm). The PFL group had significantly less lagophthalmos (0.6 ± 1.0 mm) than the AFL (1.9 ± 1.4 mm) and maximal levator resection (1.9 ± 1.7 mm) groups. In the MLR group, there was no significant difference in postoperative surgical measurements between the LF 0-2 mm group and LF 2.5-4 mm group in terms of exposure keratopathy, degree of lagophthalmos and MRD1. Conclusion MLR is an effective alternative to FS in congenital ptosis patients with poor levator function, with the risk of postoperative lagophthalmos related to postoperative MRD1 rather than preoperative LF.
Published: 2020
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37. ULTRA-WIDE FIELD FUNDUS AUTOFLUORESCENCE IMAGING OF EYES WITH STICKLER SYNDROME

Author: Kazushi Fujimoto, Shunji Kusaka, Mamika Imagawa, Kazuma Oku, Masahito Ohji, Itsuka Matsushita, Kazuki Kuniyoshi, Hiroyuki Kondo, Takaaki Hayashi, Kenichi Kimoto, and Tatsuo Nagata
Subjects: 0301 basic medicine, Retinal degeneration, Male, genetic structures, Visual Acuity, chemistry.chemical_compound, 0302 clinical medicine, Medicine, Stickler syndrome, Original Study, Fluorescein Angiography, Child, Connective Tissue Diseases, ultra-wide field, medicine.diagnostic_test, fundus autofluorescence, Optical Imaging, General Medicine, Middle Aged, Fluorescein angiography, Visual field, medicine.anatomical_structure, Child, Preschool, Female, Tomography, Optical Coherence, Adult, medicine.medical_specialty, Adolescent, Fundus Oculi, Hearing Loss, Sensorineural, 03 medical and health sciences, Young Adult, Optical coherence tomography, Ophthalmology, Humans, retinal dystrophy, Outer nuclear layer, Retrospective Studies, business.industry, Arthritis, Retinal Detachment, Retinal, medicine.disease, Fundus autofluorescence, eye diseases, 030104 developmental biology, chemistry, 030221 ophthalmology & optometry, retinal degeneration, sense organs, Visual Fields, business, Follow-Up Studies
Abstract: Supplemental Digital Content is Available in the Text. We studied 46 eyes with Stickler syndrome using ultra-widefield fundus autofluorescence images. Abnormal autofluorescence lesions were found in 81% of the eyes that were associated with age-related alteration and visual field defects., Purpose: To determine the characteristics of fundus autofluorescence (FAF) images and visual functions in eyes with Stickler syndrome using ultra-widefield FAF images. Methods: Forty-six eyes of 26 patients with mutations in the COL2A1 gene underwent ultra-widefield FAF imaging. The eyes were categorized into three types; no signs of abnormal AF, predominantly hyperfluorescent AF (hyper-AF), and predominantly hypofluorescent AF (hypo-AF). Goldmann perimetry was performed on 34 eyes, and line-scan images of the abnormal AF lesions were obtained by swept-source optical coherence tomography in 4 eyes. Results: Abnormal AF lesions were found in 37 eyes of 21 (80.7%) of the 26 patients. Hyper-AF was found in 15 eyes and hypo-AF was found in 22 eyes. The FAF changes corresponded with the funduscopically observed radial paravascular retinal degeneration. The average age at the examination was significantly younger in patients who had eyes with hyper-AF or no abnormal AF than in those with hypo-AF (12.8 vs. 28.4 years; P = 0.009). Abnormal AF-associated visual field defects were found in 5/10 (50%) eyes with hyper-AF and 17/18 (94%) eyes with hypo-AF. Hyper-AF changes tended to appear before retinal changes were detectable by fluorescein angiography. An absence of the ellipsoid zone and the outer nuclear layer and a thinning of the overall retinal thickness were found corresponding to the hypo-AF lesions in the swept source optical coherence tomography images. Conclusion: Abnormal FAF is characteristic of eyes with Stickler syndrome. Age-related alterations of the FAF was associated with visual field defects and disruption of the photoreceptors and retinal pigment epithelial cells.
Published: 2020

38. Relationship between presarcopenia and event occurrence in patients with primary hepatocellular carcinoma

Author: Fumitake Amemiya, Nobuyuki Enomoto, Tetsuya Okuwaki, Makoto Kadokura, Shinya Maekawa, Hiroki Yoda, Hitomi Takada, Keisuke Tanaka, Naoto Imagawa, Tomoki Yasumura, and Naruki Shimamura
Subjects: Male, medicine.medical_specialty, Sarcopenia, Multivariate analysis, Carcinoma, Hepatocellular, lcsh:Medicine, Gastroenterology, Article, Disease-Free Survival, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Japan, Internal medicine, Carcinoma, Biomarkers, Tumor, Medicine, Hepatectomy, Humans, In patient, lcsh:Science, Aged, Neoplasm Staging, Retrospective Studies, Multidisciplinary, business.industry, Liver Neoplasms, lcsh:R, Retrospective cohort study, Hepatology, medicine.disease, Prognosis, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Female, lcsh:Q, alpha-Fetoproteins, business
Abstract: Presarcopenia is a prognostic factor in patients with hepatocellular carcinoma (HCC). The Japan integrated staging (JIS) score is a prognostic method that combines the Child–Turcotte–Pugh classification and the tumor-node-metastasis (TNM) staging for HCC. We investigated the relationship between presarcopenia, the JIS score, and prognosis in patients with primary HCC. This retrospective study included 153 patients with primary HCC who were hospitalized from October 2011 to March 2018 at Municipal Hospital of Kofu. The skeletal muscle mass was measured using simplified psoas muscle mass index (PMI) based on CT imaging, and PMI using the volume analyzer SYNAPSE VINCENT ver3.0. We diagnosed presarcopenia based on the cut off value according to the assessment criteria for sarcopenia in liver disease defined by the Japan Society of Hepatology. Forty-three patients (28%) were diagnosed with presarcopenia. The median event-free survival was significantly worse in patients with presarcopenia than those without presarcopenia (P = 0.016). In multivariate analysis, presence of presarcopenia, JIS score ≥3, alpha-fetoprotein ≥200 ng/ml, and prothrombin induced by vitamin K absence-II ≥ 200 mAU/ml were significant prognostic factors. Among the patients with JIS scores ≥3, there was no difference in the event occurrence rate with presence of presarcopenia (P = 0.96). Among the patients with JIS scores ≤2, the median event-free-survival was significantly shorter in those with presarcopenia than those without presarcopenia (P = 0.045). Presarcopenia was an independent prognostic factor in patients with primary HCC. In patients with JIS scores ≤2, the median event-free survival was significantly shorter in those with presarcopenia compared to those without presarcopenia. In the patients with JIS scores ≥3, there was no difference in the event occurrence rates in those with and without presarcopenia.
Published: 2020
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39. Two types of fulminant type 1 diabetes mellitus: Immune checkpoint inhibitor‐related and conventional

Author: Akihisa Imagawa
Subjects: Type 1 diabetes, business.industry, Endocrinology, Diabetes and Metabolism, Immune checkpoint inhibitors, Fulminant, MEDLINE, General Medicine, Bioinformatics, medicine.disease, Antibodies, Monoclonal, Humanized, JDI Updates, RC648-665, B7-H1 Antigen, Diseases of the endocrine glands. Clinical endocrinology, Text mining, Diabetes Mellitus, Type 1, Diabetes mellitus, Internal Medicine, medicine, Humans, business, Immune Checkpoint Inhibitors
Published: 2021

40. Bilateral adrenal uptake of

Author: Yuiko, Inaba, Masaaki, Yamamoto, Shin, Urai, Masaki, Suzuki, Seiji, Nishikage, Maki, Kanzawa, Yayoi, Aoyama, Tomonori, Kanda, Katsumi, Shigemura, Hironori, Bando, Genzo, Iguchi, Yasuhiro, Nakamura, Masato, Fujisawa, Akihisa, Imagawa, Hidenori, Fukuoka, and Wataru, Ogawa
Subjects: Iodine Radioisotopes, 3-Iodobenzylguanidine, Cross-Sectional Studies, Hyperplasia, Adrenocortical Adenoma, Adrenal Gland Neoplasms, Humans, Radionuclide Imaging, Metanephrine
Abstract: Cases in which bilateral adrenal
Published: 2022

41. Usefulness of abdominal ultrasound for the diagnosis and follow‐up of gastric accessory pancreas in a child

Author: Atsushi Morita, Manabu Tagawa, Kazuo Imagawa, Masato Endo, and Hidetoshi Takada
Subjects: Stomach, Pediatrics, Perinatology and Child Health, Humans, Child, Pancreas, Congenital Abnormalities, Follow-Up Studies, Ultrasonography
Published: 2022
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42. A novel BMPR1A mutation affects mRNA splicing in juvenile polyposis syndrome

Author: Hiroko Fukushima, Kazuo Imagawa, Hidetoshi Takada, Manabu Tagawa, and Atsushi Morita
Subjects: Mutation, Intestinal Polyposis, business.industry, Juvenile Polyp, Cancer, medicine.disease, medicine.disease_cause, digestive system diseases, BMPR1A, genomic DNA, Neoplastic Syndromes, Hereditary, Pediatrics, Perinatology and Child Health, RNA splicing, medicine, Cancer research, Intronic Mutation, Humans, RNA, Female, Juvenile polyposis syndrome, RNA, Messenger, business, Bone Morphogenetic Protein Receptors, Type I, Germ-Line Mutation
Abstract: Juvenile polyposis syndrome (JPS) is one of the hereditary polyposis syndromes caused by abnormal regulation of transforming growth factor β signaling because of mutations in BMPR1A and SMAD4. Juvenile polyposis syndrome patients with SMAD4 mutations develop cardiovascular events, whereas those with BMPR1A usually do not. Analysis of genetic mutations in JPS patients can be helpful in devising suitable strategies for medical management. In this study, we demonstrate the pathogenicity of a novel intronic mutation in BMPR1A using mRNA extracted from colonic mucosa of a boy with JPS.Genomic DNA extracted from peripheral blood and total RNA isolated from the colonic mucosa were used for DNA sequencing and reverse transcription polymerase chain reaction (RT-PCR) analyses, respectively.A 13-year-old boy, with no previous medical history, presented to the hospital complaining of bloody stools. Colonoscopy revealed multiple polyps in the colon, and the resected polyps were compatible with juvenile polyps. Sequencing analysis revealed a novel intronic mutation (c.778+5GC) in BMPR1A. Reverse transcription polymerase chain reaction analysis of RNA extracted from the colonic mucosa showed an aberrant splicing form of BMPR1A. Trio analysis showed that his mother also had the same BMPR1A mutation. She was diagnosed with cancer of the cecum and polyposis of the colon at the age of 41.We demonstrate the presence of a novel BMPR1A intronic mutation that exhibits splicing abnormality in a family with JPS. Further research and development will help elucidate the genotype-phenotype relationship in JPS.
Published: 2022
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43. Quality of life of caregivers supporting neurologically impaired patients who underwent surgery

Author: Kentaro Imagawa, Suguru Fukahori, Naoki Hashizume, Nobuyuki Saikusa, Naruki Higashidate, Shinji Ishii, Daisuke Masui, Saki Sakamoto, Shiori Tsuruhisa, Hirotomo Nakahara, Yoshiaki Tanaka, Minoru Yagi, and Yushiro Yamashita
Subjects: Caregivers, Surveys and Questionnaires, Pediatrics, Perinatology and Child Health, Quality of Life, Humans, Female, Child, Aged
Abstract: A questionnaire survey was conducted to clarify whether surgical treatments performed by a pediatric surgeon improve the quality of life (QOL) of caregivers (medical doctors, nurses, physical therapists, and nursery teachers) supporting neurologically impaired (NI) patients who work at specialized institutions.The questionnaire survey was conducted with caregivers who cared for NI patients who underwent an operation at the Department of Pediatric Surgery, Kurume University Hospital. Quality-of-life related responses concerning the change of care after surgical procedures in NI patients were collected in addition to the background data related to caregivers and the surgical procedures performed for them. Degrees of difficulty in caring for NI patients and of the caregivers' own QOL postoperatively were also compared.There were 192 valid responses. The majority of responses were from females and nurses aged in their 40s and 50s. The surgical procedure performed most often in the NI patients was gastrostomy. Of the respondents, 77% answered that the postoperative care became easier. The degrees of difficulty in caring for NI patients and the caregivers' own QOL were significantly higher and lower, respectively, among physical therapists compared with caregivers in other occupations. Moreover, the QOL in respondents with factors related to a longstanding relationship with NI patients was significantly higher compared with the respondents without them.This survey indicated that surgical procedures for NI patients might contribute to improved QOL for the caregiver by reducing the difficulty of caring for NI patients.
Published: 2021

44. Time course of peripheral immunophenotypes of multisystem inflammatory syndrome in children

Author: Atsushi Morita, Sho Hosaka, Kazuo Imagawa, Takumi Ishiodori, Yoshihiro Nozaki, Takashi Murakami, and Hidetoshi Takada
Subjects: SARS-CoV-2, Immunology, Spike Glycoprotein, Coronavirus, Immunology and Allergy, COVID-19, Humans, CD8-Positive T-Lymphocytes, Child, Systemic Inflammatory Response Syndrome
Abstract: The etiology of multiple inflammatory syndrome in children (MIS-C) remains poorly understood. As clues to elucidate the pathogenic condition, several characteristic peripheral immunophenotypes have been reported in MIS-C. However, no report has demonstrated the time course of the peripheral immunophenotype along with the clinical course in the same patient. Herein, we clarified the immunological characteristics of a Japanese patient with MIS-C. There was an initial cytokine storm followed by T-cell activation, especially of CD8
Published: 2021

45. Immunological characteristics of severe acute hepatitis of unknown origin in a child post SARS-CoV-2 infection

Author: Atsushi Morita, Kazuo Imagawa, Kei Asayama, Tsubasa Terakado, Shoko Takahashi, Katsuyuki Yaita, Manabu Tagawa, Daisuke Matsubara, and Hidetoshi Takada
Subjects: SARS-CoV-2, Acute Disease, Immunology, Humans, COVID-19, Immunology and Allergy, CD8-Positive T-Lymphocytes, Child, Antibodies, Viral, Hepatitis
Abstract: Recent studies have reported that pediatric acute liver failure of unknown origin is immune-mediated, with CD8
Published: 2022
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46. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1

Author: Klionsky, Daniel, Abdel-Aziz, Amal Kamal, Abdelfatah, Sara, Abdellatif, Mahmoud, Abdoli, Asghar, Abel, Steffen, Abeliovich, Hagai, Abildgaard, Marie, Abudu, Yakubu Princely, Acevedo-Arozena, Abraham, Adamopoulos, Iannis, Adeli, Khosrow, Adolph, Timon, Adornetto, Annagrazia, Aflaki, Elma, Agam, Galila, Agarwal, Anupam, Aggarwal, Bharat, Agnello, Maria, Agostinis, Patrizia, Agrewala, Javed, Agrotis, Alexander, Aguilar, Patricia, Ahmad, S Tariq, Ahmed, Zubair, Ahumada-Castro, Ulises, Aits, Sonja, Aizawa, Shu, Akkoc, Yunus, Akoumianaki, Tonia, Akpinar, Hafize Aysin, Al-Abd, Ahmed, Al-Akra, Lina, Al-Gharaibeh, Abeer, Alaoui-Jamali, Moulay, Alberti, Simon, Alcocer-Gómez, Elísabet, Alessandri, Cristiano, Ali, Muhammad, Alim Al-Bari, M Abdul, Aliwaini, Saeb, Alizadeh, Javad, Almacellas, Eugènia, Almasan, Alexandru, Alonso, Alicia, Alonso, Guillermo, Altan-Bonnet, Nihal, Altieri, Dario, Álvarez, Élida, Alves, Sara, Alves Da Costa, Cristine, Alzaharna, Mazen, Amadio, Marialaura, Amantini, Consuelo, Amaral, Cristina, Ambrosio, Susanna, Amer, Amal, Ammanathan, Veena, An, Zhenyi, Andersen, Stig, Andrabi, Shaida, Andrade-Silva, Magaiver, Andres, Allen, Angelini, Sabrina, Ann, David, Anozie, Uche, Ansari, Mohammad, Antas, Pedro, Antebi, Adam, Antón, Zuriñe, Anwar, Tahira, Apetoh, Lionel, Apostolova, Nadezda, Araki, Toshiyuki, Araki, Yasuhiro, Arasaki, Kohei, Araújo, Wagner, Araya, Jun, Arden, Catherine, Arévalo, Maria-Angeles, Arguelles, Sandro, Arias, Esperanza, Arikkath, Jyothi, Arimoto, Hirokazu, Ariosa, Aileen, Armstrong-James, Darius, Arnauné-Pelloquin, Laetitia, Aroca, Angeles, Arroyo, Daniela, Arsov, Ivica, Artero, Rubén, Asaro, Dalia Maria Lucia, Aschner, Michael, Ashrafizadeh, Milad, Ashur-Fabian, Osnat, Atanasov, Atanas, Au, Alicia, Auberger, Patrick, Auner, Holger, Aurelian, Laure, Autelli, Riccardo, Avagliano, Laura, Ávalos, Yenniffer, Aveic, Sanja, Aveleira, Célia Alexandra, Avin-Wittenberg, Tamar, Aydin, Yucel, Ayton, Scott, Ayyadevara, Srinivas, Azzopardi, Maria, Baba, Misuzu, Backer, Jonathan, Backues, Steven, Bae, Dong-Hun, Bae, Ok-Nam, Bae, Soo Han, Baehrecke, Eric, Baek, Ahruem, Baek, Seung-Hoon, Baek, Sung Hee, Bagetta, Giacinto, Bagniewska-Zadworna, Agnieszka, Bai, Hua, Bai, Jie, Bai, Xiyuan, Bai, Yidong, Bairagi, Nandadulal, Baksi, Shounak, Balbi, Teresa, Baldari, Cosima, Balduini, Walter, Ballabio, Andrea, Ballester, Maria, Balazadeh, Salma, Balzan, Rena, Bandopadhyay, Rina, Banerjee, Sreeparna, Banerjee, Sulagna, Bánréti, Ágnes, Bao, Yan, Baptista, Mauricio, Baracca, Alessandra, Barbati, Cristiana, Bargiela, Ariadna, Barilà, Daniela, Barlow, Peter, Barmada, Sami, Barreiro, Esther, Barreto, George, Bartek, Jiri, Bartel, Bonnie, Bartolome, Alberto, Barve, Gaurav, Basagoudanavar, Suresh, Bassham, Diane, Bast, Robert, Basu, Alakananda, Batoko, Henri, Batten, Isabella, Baulieu, Etienne, Baumgarner, Bradley, Bayry, Jagadeesh, Beale, Rupert, Beau, Isabelle, Beaumatin, Florian, Bechara, Luiz, Beck, George, Beers, Michael, Begun, Jakob, Behrends, Christian, Behrens, Georg, Bei, Roberto, Bejarano, Eloy, Bel, Shai, Behl, Christian, Belaid, Amine, Belgareh-Touzé, Naïma, Bellarosa, Cristina, Belleudi, Francesca, Belló Pérez, Melissa, Bello-Morales, Raquel, Beltran, Jackeline Soares de Oliveira, Beltran, Sebastián, Benbrook, Doris Mangiaracina, Bendorius, Mykolas, Benitez, Bruno, Benito-Cuesta, Irene, Bensalem, Julien, Berchtold, Martin, Berezowska, Sabina, Bergamaschi, Daniele, Bergami, Matteo, Bergmann, Andreas, Berliocchi, Laura, Berlioz-Torrent, Clarisse, Bernard, Amélie, Berthoux, Lionel, Besirli, Cagri, Besteiro, Sebastien, Betin, Virginie, Beyaert, Rudi, Bezbradica, Jelena, Bhaskar, Kiran, Bhatia-Kissova, Ingrid, Bhattacharya, Resham, Bhattacharya, Sujoy, Bhattacharyya, Shalmoli, Bhuiyan, Md Shenuarin, Bhutia, Sujit Kumar, Bi, Lanrong, Bi, Xiaolin, Biden, Trevor, Bijian, Krikor, Billes, Viktor, Binart, Nadine, Bincoletto, Claudia, Birgisdottir, Asa, Bjorkoy, Geir, Blanco, Gonzalo, Blas-Garcia, Ana, Blasiak, Janusz, Blomgran, Robert, Blomgren, Klas, Blum, Janice, Boada-Romero, Emilio, Boban, Mirta, Boesze-Battaglia, Kathleen, Boeuf, Philippe, Boland, Barry, Bomont, Pascale, Bonaldo, Paolo, Bonam, Srinivasa Reddy, Bonfili, Laura, Bonifacino, Juan, Boone, Brian, Bootman, Martin, Bordi, Matteo, Borner, Christoph, Bornhauser, Beat, Borthakur, Gautam, Bosch, Jürgen, Bose, Santanu, botana, luis, Botas, Juan, Boulanger, Chantal, Boulton, Michael, Bourdenx, Mathieu, Bourgeois, Benjamin, Bourke, Nollaig, Bousquet, Guilhem, Boya, Patricia, Bozhkov, Peter, Bozi, Luiz, Bozkurt, Tolga, Brackney, Doug, Brandts, Christian, Braun, Ralf, Braus, Gerhard, Bravo-Sagua, Roberto, Bravo-San Pedro, José, Brest, Patrick, Bringer, Marie-Agnès, Briones-Herrera, Alfredo, Broaddus, V Courtney, Brodersen, Peter, Brodsky, Jeffrey, Brody, Steven, Bronson, Paola, Bronstein, Jeff, Brown, Carolyn, Brown, Rhoderick, Brum, Patricia, Brumell, John, Brunetti-Pierri, Nicola, Bruno, Daniele, Bryson-Richardson, Robert, 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Sylvie, Giustiniani, Julien, Gluschko, Alexander, Goder, Veit, Goginashvili, Alexander, Golab, Jakub, Goldstone, David, Golebiewska, Anna, Gomes, Luciana, Gomez, Rodrigo, Gómez-Sánchez, Rubén, Gomez-Puerto, Maria Catalina, Gomez-Sintes, Raquel, Gong, Qingqiu, Goni, Felix, González-Gallego, Javier, Gonzalez-Hernandez, Tomas, Gonzalez-Polo, Rosa, Gonzalez-Reyes, Jose, González-Rodríguez, Patricia, Goping, Ing Swie, Gorbatyuk, Marina, Gorbunov, Nikolai, Görgülü, Kıvanç, Gorojod, Roxana, Gorski, Sharon, Goruppi, Sandro, Gotor, Cecilia, Gottlieb, Roberta, Gozes, Illana, Gozuacik, Devrim, Graef, Martin, Gräler, Markus, Granatiero, Veronica, Grasso, Daniel, Gray, Joshua, Green, Douglas, Greenhough, Alexander, Gregory, Stephen, Griffin, Edward, Grinstaff, Mark, Gros, Frederic, Grose, Charles, Gross, Angelina, Gruber, Florian, Grumati, Paolo, Grune, Tilman, Gu, Xueyan, Guan, Jun-Lin, Guardia, Carlos, Guda, Kishore, Guerra, Flora, Guerri, Consuelo, Guha, Prasun, Guillén, Carlos, Gujar, Shashi, 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Chengyu, Liang, Qiangrong, Liang, Weicheng, Liang, Yongheng, Liang, YongTian, Liao, Guanghong, Liao, Lujian, Liao, Mingzhi, Liao, Yung-Feng, Librizzi, Mariangela, Lie, Pearl, Lilly, Mary, Lim, Hyunjung, Lima, Thania, Limana, Federica, Lin, Chao, Lin, Chih-Wen, Lin, Dar-Shong, Lin, Fu-Cheng, Lin, Jiandie, Lin, Kurt, Lin, Kwang-Huei, Lin, Liang-Tzung, LIN, Pei-Hui, Lin, Qiong, Lin, Shaofeng, Lin, Su-Ju, Lin, Wenyu, Lin, Xueying, Lin, Yao-Xin, Lin, Yee-Shin, Linden, Rafael, Lindner, Paula, Ling, Shuo-Chien, Lingor, Paul, Linnemann, Amelia, Liou, Yih-Cherng, Lipinski, Marta, Lipovšek, Saška, Lira, Vitor, Lisiak, Natalia, Liton, Paloma, Liu, Chao, Liu, Ching-Hsuan, Liu, Chun-Feng, Liu, Cui Hua, Liu, Fang, Liu, Hao, Liu, Hsiao-Sheng, Liu, Hua-feng, Liu, Huifang, Liu, Jia, Liu, Jing, Liu, Julia, Liu, Leyuan, Liu, Longhua, Liu, Meilian, Liu, Qin, Liu, Wei, Liu, Wende, Liu, Xiao-Hong, Liu, Xiaodong, Liu, Xingguo, Liu, Xu, Liu, Xuedong, Liu, Yanfen, Liu, Yang, Liu, Yueyang, Liu, Yule, 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Jiangang, Shen, Ming, Shen, Weili, Shen, Zheni, Sheng, Rui, Sheng, Zhi, Sheng, Zu-Hang, Shi, Jianjian, Shi, Xiaobing, Shi, Ying-Hong, Shiba-Fukushima, Kahori, Shieh, Jeng-Jer, Shimada, Yohta, Shimizu, Shigeomi, Shimozawa, Makoto, Shintani, Takahiro, Shoemaker, Christopher, Shojaei, Shahla, Shoji, Ikuo, Shravage, Bhupendra, Shridhar, Viji, Shu, Chih-Wen, Shu, Hong-Bing, Shui, Ke, Shukla, Arvind, Shutt, Timothy, Sica, Valentina, Siddiqui, Aleem, Sierra, Amanda, Sierra-Torre, Virginia, Signorelli, Santiago, Sil, Payel, Silva, Bruno, Silva, Johnatas, Silva-Pavez, Eduardo, Silvente-Poirot, Sandrine, Simmonds, Rachel, Simon, Anna Katharina, Simon, Hans-Uwe, Simons, Matias, Singh, Anurag, Singh, Lalit, Singh, Rajat, Singh, Shivendra, Singh, Shrawan, Singh, Sudha, Singh, Sunaina, Singh, Surinder Pal, Sinha, Debasish, Sinha, Rohit Anthony, Sinha, Sangita, Sirko, Agnieszka, Sirohi, Kapil, Sivridis, Efthimios, Skendros, Panagiotis, Skirycz, Aleksandra, Slaninová, Iva, Smaili, Soraya, Smertenko, Andrei, Smith, Matthew, Soenen, Stefaan, Sohn, Eun Jung, Sok, Sophia, Solaini, Giancarlo, Soldati, Thierry, Soleimanpour, Scott, Soler, Rosa, Solovchenko, Alexei, Somarelli, Jason, Sonawane, Avinash, Song, Fuyong, Song, Hyun Kyu, Song, Ju-Xian, Song, Kunhua, Song, Zhiyin, Soria, Leandro, Sorice, Maurizio, Soukas, Alexander, Soukup, Sandra-Fausia, Sousa, Diana, Sousa, Nadia, Spagnuolo, Paul, Spector, Stephen, Srinivas Bharath, M., St Clair, Daret, Stagni, Venturina, Staiano, Leopoldo, Stalnecker, Clint, Stankov, Metodi, Stathopulos, Peter, Stefan, Katja, Stefan, Sven Marcel, Stefanis, Leonidas, Steffan, Joan, Steinkasserer, Alexander, Stenmark, Harald, Sterneckert, Jared, Stevens, Craig, Stoka, Veronika, Storch, Stephan, Stork, Björn, Strappazzon, Flavie, Strohecker, Anne Marie, Stupack, Dwayne, Su, Huanxing, Su, Ling-Yan, Su, Longxiang, Suarez-Fontes, Ana, Subauste, Carlos, Subbian, Selvakumar, Subirada, Paula, Sudhandiran, Ganapasam, Sue, Carolyn, Sui, Xinbing, Summers, Corey, Sun, Guangchao, Sun, Jun, SUN, Kang, Sun, Meng-xiang, Sun, Qiming, Sun, Yi, Sun, Zhongjie, Sunahara, Karen, Sundberg, Eva, Susztak, Katalin, Sutovsky, Peter, Suzuki, Hidekazu, Sweeney, Gary, Symons, J David, Sze, Stephen Cho Wing, Szewczyk, Nathaniel, Tabęcka-Łonczynska, Anna, Tabolacci, Claudio, Tacke, Frank, Taegtmeyer, Heinrich, Tafani, Marco, Tagaya, Mitsuo, Tai, Haoran, Tait, Stephen, Takahashi, Yoshinori, Takats, Szabolcs, Talwar, Priti, Tam, Chit, Tam, Shing Yau, Tampellini, Davide, Tamura, Atsushi, Tan, Chong Teik, Tan, Eng-King, Tan, Ya-Qin, Tanaka, Masaki, Tanaka, Motomasa, Tang, Daolin, Tang, Jingfeng, Tang, Tie-Shan, Tanida, Isei, Tao, Zhipeng, Taouis, Mohammed, Tatenhorst, Lars, Tavernarakis, Nektarios, Taylor, Allen, Taylor, Gregory, Taylor, Joan, Tchetina, Elena, Tee, Andrew, Tegeder, Irmgard, Teis, David, Teixeira, Natercia, Teixeira-Clerc, Fatima, Tekirdag, Kumsal, Tencomnao, Tewin, Tenreiro, Sandra, Tepikin, Alexei, Testillano, Pilar, Tettamanti, Gianluca, Tharaux, Pierre-Louis, Thedieck, Kathrin, Thekkinghat, Arvind, Thellung, Stefano, Thinwa, Josephine, Thirumalaikumar, V.P., Thomas, Sufi Mary, Thomes, Paul, Thorburn, Andrew, Thukral, Lipi, Thum, Thomas, Thumm, Michael, Tian, Ling, Tichy, Ales, Till, Andreas, Timmerman, Vincent, Titorenko, Vladimir, Todi, Sokol, Todorova, Krassimira, Toivonen, Janne, Tomaipitinca, Luana, Tomar, Dhanendra, Tomas-Zapico, Cristina, Tomić, Sergej, Tong, Benjamin Chun-Kit, Tong, Chao, Tong, Xin, Tooze, Sharon, Torgersen, Maria, Torii, Satoru, Torres-López, Liliana, Torriglia, Alicia, Towers, Christina, Towns, Roberto, Toyokuni, Shinya, Trajkovic, Vladimir, Tramontano, Donatella, Tran, Quynh-Giao, Travassos, Leonardo, Trelford, Charles, Tremel, Shirley, Trougakos, Ioannis, Tsao, Betty, Tschan, Mario, Tse, Hung-Fat, Tse, Tak Fu, Tsugawa, Hitoshi, Tsvetkov, Andrey, Tumbarello, David, Tumtas, Yasin, Tuñón, María, Turcotte, Sandra, Turk, Boris, Turk, Vito, Turner, Bradley, Tuxworth, Richard, Tyler, Jessica, Tyutereva, Elena, Uchiyama, Yasuo, Ugun-Klusek, Aslihan, Uhlig, Holm, Ułamek-Kozioł, Marzena, Ulasov, Ilya, Umekawa, Midori, Ungermann, Christian, Unno, Rei, Urbe, Sylvie, Uribe-Carretero, Elisabet, Üstün, Suayib, Uversky, Vladimir, Vaccari, Thomas, Vaccaro, Maria, Vahsen, Björn, Vakifahmetoglu-Norberg, Helin, Valdor, Rut, Valente, Maria, Valko, Ayelén, Vallee, Richard, Valverde, Angela, Van Den Berghe, Greet, van der Veen, Stijn, Van Kaer, Luc, van Loosdregt, Jorg, van Wijk, Sjoerd, Vandenberghe, Wim, Vanhorebeek, Ilse, Vannier-Santos, Marcos, Vannini, Nicola, Vanrell, M Cristina, Vantaggiato, Chiara, Varano, Gabriele, Varela-Nieto, Isabel, Varga, Máté, Vasconcelos, M Helena, Vats, Somya, Vavvas, Demetrios, Vega-Naredo, Ignacio, Vega-Rubin-de-Celis, Silvia, Velasco, Guillermo, Velázquez, Ariadna, Vellai, Tibor, Vellenga, Edo, Velotti, Francesca, Verdier, Mireille, Verginis, Panayotis, Vergne, Isabelle, Verkade, Paul, Verma, Manish, Verstreken, Patrik, Vervliet, Tim, Vervoorts, Jörg, Vessoni, Alexandre, Victor, Victor, Vidal, Michel, Vidoni, Chiara, Vieira, Otilia, Vierstra, Richard, Viganó, Sonia, Vihinen, Helena, Vijayan, Vinoy, Vila, Miquel, Vilar, Marçal, Villalba, José, Villalobo, Antonio, Villarejo-Zori, Beatriz, Villarroya, Francesc, Villarroya, Joan, Vincent, Olivier, Vindis, Cecile, Viret, Christophe, Viscomi, Maria Teresa, Visnjic, Dora, Vitale, Ilio, Vocadlo, David, Voitsekhovskaja, Olga, Volonté, Cinzia, Volta, Mattia, Vomero, Marta, Von Haefen, Clarissa, Vooijs, Marc, Voos, Wolfgang, Vucicevic, Ljubica, Wade-Martins, Richard, Waguri, Satoshi, Waite, Kenrick, Wakatsuki, Shuji, Walker, David, Walker, Mark, Walker, Simon, Walter, Jochen, Wandosell, Francisco, Wang, Bo, Wang, Chao-Yung, Wang, Chen, Wang, Chenran, Wang, Chenwei, Wang, Cun-Yu, Wang, Dong, Wang, Fangyang, Wang, Feng, Wang, Fengming, Wang, Guansong, Wang, Han, Wang, Hao, Wang, Hexiang, Wang, Hong-Gang, Wang, Jianrong, Wang, Jigang, Wang, Jiou, Wang, Jundong, Wang, Kui, Wang, Lianrong, Wang, Liming, Wang, Maggie Haitian, Wang, Meiqing, Wang, Nanbu, Wang, PengWei, Wang, PeiPei, Wang, Ping, Wang, Qing Jun, Wang, Qing, Wang, Qing Kenneth, Wang, Qiong, Wang, Wen-Tao, Wang, Wuyang, Wang, Xinnan, Wang, Xuejun, Wang, Yan, Wang, Yanchang, Wang, Yanzhuang, Wang, Yen-Yun, Wang, Yihua, Wang, Yipeng, Wang, Yu, wang, yuqi, Wang, Zhe, Wang, Zhenyu, Wang, Zhouguang, Warnes, Gary, Warnsmann, Verena, Watada, Hirotaka, Watanabe, Eizo, Watchon, Maxinne, Wawrzyńska, Anna, Weaver, Timothy, Wegrzyn, Grzegorz, Wehman, Ann, Wei, Huafeng, Wei, Lei, Wei, Taotao, Wei, Yongjie, Weiergräber, Oliver, Weihl, Conrad, Weindl, Günther, Weiskirchen, Ralf, Wells, Alan, Wen, Runxia, Wen, Xin, Werner, Antonia, Weykopf, Beatrice, Wheatley, Sally, Whitton, J Lindsay, Whitworth, Alexander, Wiktorska, Katarzyna, Wildenberg, Manon, Wileman, Tom, Wilkinson, Simon, Willbold, Dieter, Williams, Brett, Williams, Robin, Williams, Roger, Williamson, Peter, Wilson, Richard, Winner, Beate, Winsor, Nathaniel, Witkin, Steven, Wodrich, Harald, Woehlbier, Ute, Wollert, Thomas, Wong, Esther, Wong, Jack Ho, Wong, Richard, Wong, Vincent Kam Wai, Wong, W Wei-Lynn, Wu, An-Guo, Wu, Chengbiao, Wu, Jian, Wu, Junfang, Wu, Kenneth, Wu, Min, Wu, Shan-Ying, Wu, Shengzhou, Wu, Shu-Yan, Wu, Shufang, Wu, William, Wu, Xiaohong, Wu, Xiaoqing, Wu, Yao-Wen, Wu, Yihua, Xavier, Ramnik, Xia, Hongguang, Xia, Lixin, Xia, Zhengyuan, Xiang, Ge, Xiang, Jin, Xiang, Mingliang, Xiang, Wei, Xiao, Bin, Xiao, Guozhi, Xiao, Hengyi, Xiao, Hong-tao, Xiao, Jian, Xiao, Lan, Xiao, Shi, Xiao, Yin, Xie, Baoming, Xie, Chuan-Ming, Xie, Min, Xie, Yuxiang, Xie, Zhiping, Xie, Zhonglin, Xilouri, Maria, Xu, Congfeng, Xu, En, Xu, Haoxing, Xu, Jing, Xu, Jinrong, Xu, Liang, Xu, Wen Wen, Xu, Xiulong, Xue, Yu, Yakhine-Diop, Sokhna, Yamaguchi, Masamitsu, Yamaguchi, Osamu, Yamamoto, Ai, Yamashina, Shunhei, Yan, Shengmin, Yan, Shian-Jang, Yan, Zhen, Yanagi, Yasuo, Yang, Chuanbin, Yang, Dun-Sheng, Yang, Huan, Yang, Huang-Tian, Yang, Hui, Yang, Jin-Ming, Yang, Jing, Yang, Jingyu, Yang, Ling, Yang, Liu, Yang, Ming, Yang, Pei-Ming, Yang, Qian, Yang, Seungwon, Yang, Shu, Yang, Shun-Fa, Yang, Wannian, Yang, Wei Yuan, Yang, Xiaoyong, Yang, Xuesong, Yang, Yi, Yang, Ying, Yao, Honghong, Yao, Shenggen, Yao, Xiaoqiang, Yao, Yong-Gang, Yao, Yong-Ming, Yasui, Takahiro, Yazdankhah, Meysam, Yen, Paul, Yi, Cong, Yin, Xiao-Ming, Yin, Yanhai, Yin, Zhangyuan, Yin, Ziyi, Ying, Meidan, Ying, Zheng, Yip, Calvin, Yiu, Stephanie Pei Tung, Yoo, Young, Yoshida, Kiyotsugu, Yoshii, Saori, Yoshimori, Tamotsu, Yousefi, Bahman, Yu, Boxuan, Yu, Haiyang, Yu, Jun, Yu, Li, Yu, Ming-Lung, Yu, Seong-Woon, Yu, Victor, Yu, W Haung, Yu, Zhengping, Yu, Zhou, Yuan, Junying, Yuan, Ling-Qing, Yuan, Shilin, Yuan, Shyng-Shiou, Yuan, Yanggang, Yuan, Zengqiang, Yue, Jianbo, Yue, Zhenyu, Yun, Jeanho, Yung, Raymond, Zacks, David, Zaffagnini, Gabriele, Zambelli, Vanessa, Zanella, Isabella, Zang, Qun, Zanivan, Sara, Zappavigna, Silvia, Zaragoza, Pilar, Zarbalis, Konstantinos, Zarebkohan, Amir, Zarrouk, Amira, Zeitlin, Scott, Zeng, Jialiu, Zeng, Ju-deng, Žerovnik, Eva, Zhan, Lixuan, Zhang, Bin, Zhang, Donna, Zhang, Hanlin, Zhang, Hong, Zhang, Honghe, Zhang, Huafeng, Zhang, Huaye, Zhang, Hui, Zhang, Hui-Ling, Zhang, Jianbin, Zhang, Jianhua, Zhang, Jing-Pu, Zhang, Kalin, Zhang, Leshuai, Zhang, Lin, Zhang, Lisheng, Zhang, Lu, Zhang, Luoying, Zhang, Menghuan, Zhang, Peng, Zhang, Sheng, Zhang, Wei, Zhang, Xiangnan, Zhang, Xiao-Wei, Zhang, Xiaolei, Zhang, Xiaoyan, Zhang, Xin, Zhang, Xinxin, Zhang, Xu Dong, Zhang, Yang, Zhang, Yanjin, Zhang, Yi, Zhang, Ying-Dong, Zhang, Yingmei, Zhang, Yuan-Yuan, Zhang, Yuchen, Zhang, Zhe, Zhang, Zhengguang, Zhang, Zhibing, Zhang, Zhihai, Zhang, Zhiyong, Zhang, Zili, Zhao, Haobin, Zhao, Lei, Zhao, Shuang, Zhao, Tongbiao, Zhao, Xiao-Fan, Zhao, Ying, Zhao, Yongchao, Zhao, Yongliang, Zhao, Yuting, Zheng, Guoping, Zheng, Kai, Zheng, Ling, Zheng, Shizhong, Zheng, Xi-Long, Zheng, Yi, Zheng, Zu-Guo, Zhivotovsky, Boris, Zhong, Qing, Zhou, Ao, Zhou, Ben, Zhou, Cefan, ZHOU, Gang, Zhou, Hao, Zhou, Hong, Zhou, Hongbo, Zhou, Jie, Zhou, Jing, Zhou, Jiyong, Zhou, Kailiang, Zhou, Rongjia, Zhou, Xu-jie, Zhou, Yanshuang, Zhou, Yinghong, Zhou, Yubin, Zhou, Zheng-Yu, Zhou, Zhou, Zhu, Binglin, Zhu, Changlian, Zhu, Guo-Qing, Zhu, Haining, Zhu, Hongxin, Zhu, Hua, Zhu, Wei-Guo, Zhu, Yanping, Zhu, Yushan, Zhuang, Haixia, Zhuang, Xiaohong, Zientara-Rytter, Katarzyna, Zimmermann, Christine, Ziviani, Elena, Zoladek, Teresa, Zong, Wei-Xing, Zorov, Dmitry, Zorzano, Antonio, Zou, Weiping, Zou, Zhen, Zou, Zhengzhi, Zuryn, Steven, Zwerschke, Werner, Brand-Saberi, Beate, Dong, X Charlie, Kenchappa, Chandra Shekar, Li, Zuguo, Lin, Yong, Oshima, Shigeru, Rong, Yueguang, Sluimer, Judith, Stallings, Christina, Tong, Chun-Kit, Ahmad, S. Tariq, Alim Al-Bari, M. Abdul, Bechara, Luiz R.G., Behrens, Georg M.N., Bhuiyan, Md. Shenuarin, Broaddus, V. Courtney, Buchan, J. Ross, Burón, M. Isabel, Carter, A. Brent, Chan, Matthew T.V., Choi, Augustine M.K., D’Adamo, Stefania, D’Amelio, Marcello, D’Arcangelo, Daniela, D’Lugos, Andrew, D’Orazi, Gabriella, De Meyer, Guido R.Y., Delpino, M. Victoria, Distler, Jörg H.W., Dixon, Ian M.C., Dobson, Renwick C.J., 2nd Dorn, Gerald, Eissa, N. Tony, Engelsen, Agnete S.T., Fairlie, W. Douglas, Ferreira, Julio C.B., H.B., Ranjitha, Hanson, Phyllis I., Hejtmancik, J. Fielding, Ho, Idy H.T., Hobbs, G. Aaron, Hoet, Peter H.M., Huang, Michael L.H., Iyer, Anand Krishnan V., Johnson, Gail V.W., Joosten, Leo A.B., Karim, Md. Razaul, Kaufmann, Stefan H.E., Ko, Ben C.B., Leck, Lionel Y.W., Lima, Thania R.R., Livingston, J. Andrew, Martin, Alexandre P.J., Montes, L. Ruth, Murphy, J. Patrick, Ng, Charlene C.W., Nicolao, M. Celeste, O’Donovan, Tracey, O’Leary, Seónadh, O’Rourke, Eyleen, O’Sullivan, Mary, O’Sullivan, Timothy, Omary, M. Bishr, Pereira, Gustavo J.S., Ratnayaka, J. Arjuna, Riazuddin, S. Amer, Rouschop, Kasper M.A., Sanderson, J. Thomas, Scaglione, K. Matthew, Schapira, Anthony H.V., Scovassi, A. Ivana, St. Clair, Daret, Sunahara, Karen K.S., Symons, J. David, Triola, Gemma, van Wijk, Sjoerd J.L., Vanrell, M. Cristina, Vasconcelos, M. Helena, Whitton, J. Lindsay, Williams, Robin S.B., Wong, W. Wei-Lynn, Wu, William K.K., Yakhine-Diop, Sokhna M.S., Yu, W. Haung, Zhang, Kalin Y.B., Dong, X. Charlie, Ain Shams University [ASU], Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University [JGU], Medical University Graz, Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)], Institut Pasteur d'Iran, Leibniz Institute of Plant Biochemistry [IPB], The University of Texas M.D. Anderson Cancer Center [Houston], Institut de pharmacologie moléculaire et cellulaire [IPMC], Lipides - Nutrition - Cancer [Dijon - U1231] [LNC], Centre méditerranéen de médecine moléculaire [C3M], Institut de Biologie Valrose [IBV], Petites Molécules de neuroprotection, neurorégénération et remyélinisation, Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, Institut Cochin [IC UM3 (UMR 8104 / U1016)], Institut NeuroMyoGène [INMG], Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)], Marqueurs cardiovasculaires en situation de stress [MASCOT (UMR_S_942 / U942)], Institut de Recherche sur le Cancer et le Vieillissement [IRCAN], Centre de Recherche en Cancérologie de Marseille [CRCM], Centre for Integrative Biology - CBI [Inserm U964 - CNRS UMR7104 - IGBMC], Oncogenesis, Stress, Signaling [OSS], Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)], Institut de Biologie Intégrative de la Cellule [I2BC], Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte [M2iSH], Centre de Recherches en Cancérologie de Toulouse [CRCT], Physiopathologie et traitement des maladies du foie, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Institut de Génétique et de Biologie Moléculaire et Cellulaire [IGBMC], Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] [BIO-PEROXIL], Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)], Unité de génétique et biologie des cancers [U830], Laboratoire d'Optique et Biosciences [LOB], Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC], Différenciation et communication neuronale et neuroendocrine [DC2N], Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM], Centre d'Immunologie de Marseille - Luminy [CIML], Physiopathologie et imagerie des troubles neurologiques [PhIND], Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée [LBFA], Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163], Institut Mondor de Recherche Biomédicale [IMRB], Franco-czech Laboratory for clinical research on obesity, University of Michigan [Ann Arbor], University of Michigan System, Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de Biologie Valrose (IBV), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Nutrition, Métabolisme, Aquaculture (NuMéA), Université de Pau et des Pays de l'Adour (UPPA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institute of genetics and molecular and cellular biology-Centre National de la Recherche Scientifique (CNRS), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut Jean-Pierre Bourgin (IJPB), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epithelial biology and disease - Liliane Bettencourt Chair of Developmental Biology (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the National Institute of General Medical Sciences [GM131919]., Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Département Plateforme (PF I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Chinese Academy of Medical Sciences [Suzhou, Chine] (CAMS), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Department of Women's and Children's Health [Stockholm, Sweden], Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École polytechnique (X), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Life Sciences Institute [Ann Arbor, MI, USA], University of Michigan System-University of Michigan System, European Institute of Oncology IRCCS [Milan, Italy] (EIO), Ain Shams University (ASU), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Réseau International des Instituts Pasteur (RIIP), Leibniz Institute of Plant Biochemistry (IPB), Hebrew University of Jerusalem, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Oncogenesis, Stress, Signaling (OSS), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Klionsky, D. 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C., Brodersen, P., Brodsky, J. L., Brody, S. L., Bronson, P. G., Bronstein, J. M., Brown, C. N., Brown, R. E., Brum, P. C., Brumell, J. H., Brunetti-Pierri, N., Bruno, D., Bryson-Richardson, R. J., Bucci, C., Buchrieser, C., Bueno, M., Buitrago-Molina, L. E., Buraschi, S., Buch, S., Buchan, J. R., Buckingham, E. M., Budak, H., Budini, M., Bultynck, G., Burada, F., Burgoyne, J. R., Buron, M. I., Bustos, V., Buttner, S., Butturini, E., Byrd, A., Cabas, I., Cabrera-Benitez, S., Cadwell, K., Cai, J., Cai, L., Cai, Q., Cairo, M., Calbet, J. A., Caldwell, G. A., Caldwell, K. A., Call, J. A., Calvani, R., Calvo, A. C., Calvo-Rubio Barrera, M., Camara, N. O. S., Camonis, J. H., Camougrand, N., Campanella, M., Campbell, E. M., Campbell-Valois, F. -X., Campello, S., Campesi, I., Campos, J. C., Camuzard, O., Cancino, J., Candido de Almeida, D., Canesi, L., Caniggia, I., Canonico, B., Canti, C., Cao, B., Caraglia, M., Carames, B., Carchman, E. 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E., Chung, H., Chung, K. P., Chung, S., Chung, S. -H., Chung, Y. -L., Cianfanelli, V., Ciechomska, I. A., Cifuentes, M., Cinque, L., Cirak, S., Cirone, M., Clague, M. J., Clarke, R., Clementi, E., Coccia, E. M., Codogno, P., Cohen, E., Cohen, M. M., Colasanti, T., Colasuonno, F., Colbert, R. A., Colell, A., Colic, M., Coll, N. S., Collins, M. O., Colombo, M. I., Colon-Ramos, D. A., Combaret, L., Comincini, S., Cominetti, M. R., Consiglio, A., Conte, A., Conti, F., Contu, V. R., Cookson, M. R., Coombs, K. M., Coppens, I., Corasaniti, M. T., Corkery, D. P., Cordes, N., Cortese, K., Costa, M. D. C., Costantino, S., Costelli, P., Coto-Montes, A., Crack, P. J., Crespo, J. L., Criollo, A., Crippa, V., Cristofani, R., Csizmadia, T., Cuadrado, A., Cui, B., Cui, J., Cui, Y., Culetto, E., Cumino, A. C., Cybulsky, A. V., Czaja, M. J., Czuczwar, S. J., D'Adamo, S., D'Amelio, M., D'Arcangelo, D., D'Lugos, A. C., D'Orazi, G., da Silva, J. A., Dafsari, H. S., Dagda, R. 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Subjects: 0301 basic medicine, Programmed cell death, Settore BIO/06, Autophagosome, Autolysosome, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Autophagy-Related Proteins, Review, Computational biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Settore MED/04, 03 medical and health sciences, stress, Chaperone-mediated autophagy, ddc:570, Autophagy, LC3, Animals, Humans, cancer, Settore BIO/10, flux, lysosome, macroautophagy, neurodegeneration, phagophore, vacuole, Set (psychology), Molecular Biology, 030102 biochemistry & molecular biology, business.industry, Interpretation (philosophy), Autophagosomes, Cell Biology, Multicellular organism, 030104 developmental biology, Knowledge base, Biological Assay, Lysosomes, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Contains fulltext : 232759.pdf (Publisher’s version ) (Closed access) In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
Published: 2021
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47. Grip Strength as a Predictor of the Functional Outcome of Hip-Fracture Patients

Author: Hiromi Imagawa, Takahiro Higuchi, Naoto Shiba, Yumi Miruno, Kazuhito Minamitani, Yoko Muta, Sohei Iwanaga, Hiroo Matsuse, Asami Kubota, Ryuki Hashida, Yohei Hirakawa, and Masafumi Bekki
Subjects: Male, medicine.medical_specialty, Bone density, Walking, Physical strength, Logistic regression, Body Mass Index, Grip strength, Bone Density, Medicine, Humans, Femoral neck, Aged, Aged, 80 and over, Hip fracture, Hand Strength, business.industry, Hip Fractures, General Medicine, medicine.disease, Functional Independence Measure, Hospitals, Patient Discharge, medicine.anatomical_structure, Treatment Outcome, Physical therapy, Female, business, human activities, Body mass index
Abstract: BACKGROUND Patients with hip fracture are limited as to physical activity. It is difficult to evaluate the physical function of the legs at admission; however, it is easy to measure grip strength, which has been reported to be correlated with systemic muscular strength and physical function. The objective of this study was to investigate the utility of grip strength in predicting functional outcome after hip fracture. METHODS Fifty-seven patients who underwent surgery for hip fracture were evaluated for height, weight, Body Mass Index (BMI), grip strength, bone density (femoral neck), hemoglobin, Hemoglobin A1c (HbA1c), Hasegawa's Dementia Scale-Revised (HDS-R), and albumin at admission and Functional Independence Measure (FIM) at discharge. Spearman's rank correlation coefficient was used to evaluate the relation between grip strength and the above variables. Furthermore, factors of walking acquisition were analyzed by logistic regression analysis and decision-tree analysis. RESULTS Correlation analysis showed that grip strength was positively correlated with bone density at admission and FIM at discharge and negatively correlated with age. In the logistic regression analysis, the independent factor associated with walking acquisition was grip strength (OR 1.26; 95%CI 1.018-1.566; p=0.0339). In the decisiontree analysis, grip strength was the initial divergence variable for walking acquisition (the percentage with walking acquisition was 80.0% of the patients with grip strength ≧13.2 kg VS. 18.7% of the patients with grip strength < 13.2 kg). CONCLUSIONS Grip strength at admission was definitive in predicting the functional outcome of patients with hip fracture who underwent surgery.
Published: 2021

48. Pneumococcal Serotype-specific Opsonophagocytic Activity in Interleukin-1 Receptor-associated Kinase 4-deficient Patients: ERRATUM

Author: Shiho Nishimura, Saeko Morino, Kazunori Oishi, Hiroko Fukushima, Tomoko Uehara, Satoshi Okada, Hidetoshi Takada, Yukitsugu Nakamura, Asao Yara, Kazuo Imagawa, Noriko Togashi, and Masue Imaizumi
Subjects: Male, Microbiology (medical), Serotype, Adolescent, medicine.drug_class, Primary Immunodeficiency Diseases, Antibiotics, Serogroup, medicine.disease_cause, Pneumococcal Infections, Pneumococcal Vaccines, 03 medical and health sciences, 0302 clinical medicine, Japan, Antigen, Opsonization, 030225 pediatrics, Streptococcus pneumoniae, medicine, Humans, 030212 general & internal medicine, Serotyping, Child, business.industry, medicine.disease, Antibodies, Bacterial, Pneumococcal polysaccharide vaccine, Vaccination, Interleukin-1 Receptor-Associated Kinases, Infectious Diseases, Pneumococcal vaccine, Child, Preschool, Antibody Formation, Pediatrics, Perinatology and Child Health, Immunology, Female, business, Meningitis
Abstract: Background The antibody response after pneumococcal vaccines and their effectiveness against invasive pneumococcal disease (IPD) in patients with interleukin-1 receptor-associated kinase 4 (IRAK4) deficiency have not been fully evaluated. Here, we evaluated pneumococcal serotype-specific opsonophagocytic activity (OPA) in IRAK4-deficient patients along with their clinical course. Methods We investigated 6 IRAK4-deficient patients in Japan, whose attending physicians could be contacted. We performed OPA measurements using stored and more recent serum samples obtained from these patients. Results All patients had received pneumococcal vaccination. Among the 3 patients who had IPD, 2 had an episode of pneumococcal meningitis and the other developed pneumococcal bacteremia 3 years after the occurrence of pneumococcal meningitis. Only one episode of invasive bacterial infection was caused by a Streptococcus pneumoniae vaccine-type strain. An increased opsonization index was found in the sera after vaccination for all IRAK-deficient patients, including when the 23-valent pneumococcal polysaccharide vaccine was used. Conclusions A significant increase in levels of OPA against most of the pneumococcal vaccine antigens was observed for all IRAK4-deficient patients. However, IPD could not be prevented by pneumococcal vaccination alone. Therefore, adequate prophylaxis should be provided with antibiotics at least until 8 years of age, along with regular immunoglobulin therapy, particularly during the infantile period.
Published: 2021

49. Fulminant type 1 diabetes patients display high frequencies of IGRP-specific type 1 CD8

Author: Toshiaki Hanafusa, Hiroshi Kajio, Akitsu Kawabe, Kohjiro Ueki, Fumitaka Haseda, Kazuyuki Tobe, Akihisa Imagawa, Daisuke Chujo, Maya Matsushita, Chiharu Tsutsumi, Masayuki Shimoda, and Kunimasa Yagi
Subjects: Adult, Male, endocrine system, medicine.medical_treatment, T cell, Immunology, CD8-Positive T-Lymphocytes, medicine.disease_cause, Peripheral blood mononuclear cell, Autoimmunity, Pathogenesis, medicine, Immunology and Allergy, Cytotoxic T cell, Humans, Type 1 diabetes, business.industry, Middle Aged, medicine.disease, Cytokine, medicine.anatomical_structure, Diabetes Mellitus, Type 1, Glucose-6-Phosphatase, Female, business, CD8
Abstract: The role of cellular autoimmunity in the pathogenesis of fulminant type 1 diabetes (FT1D) remains largely unknown. In this study, we performed an integrated assay using peripheral blood mononuclear cells to determine the islet antigen-specific CD8+ T cell responses in FT1D and compare the responses among acute-onset T1D (AT1D) and slowly progressive T1D (SP1D). IGRP- and ZnT8-specific IL-6, G-CSF, and TNF-α responses were significantly upregulated in patients with FT1D, while IGRP- and ZnT8-specific IP-10 responses were significantly upregulated in patients with AT1D than in non-diabetics (ND). Furthermore, the frequencies of IGRP-specific type 1 CD8+ cytotoxic T (Tc1) cells were significantly higher in the FT1D group than in the ND, SP1D, and AT1D groups. Additionally, IGRP-specific Tc1 cells were more abundant in the FT1D with HLA-A2 group than in the FT1D without A2 group. In conclusion, our study suggests that IGRP-specific CD8+ T cells significantly contribute to the pathogenesis of FT1D.
Published: 2021

50. Intra-Operative Abdominal Drain Placement for Gallbladder Cancer Surgery and Risk of Infectious Complications

Author: Zeljka Jutric, Jeffry Nahmias, Areg Grigorian, Ronald F. Wolf, David K. Imagawa, Maki Yamamoto, and Bima J Hasjim
Subjects: Microbiology (medical), medicine.medical_specialty, Intra operative, Blood transfusion, business.industry, medicine.medical_treatment, medicine.disease, Surgery, Infectious Diseases, Postoperative Complications, medicine, Drainage, Humans, Cholecystectomy, Gallbladder Neoplasms, Stents, Gallbladder cancer, business, Bile leak, Retrospective Studies
Abstract: Background: Routine intra-operative abdominal drain placement (IADP) is not beneficial for uncomplicated cholecystectomies though outcomes in gallbladder cancer surgery is unclear. This retrospecti...
Published: 2021

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