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3. A case of vasculogenic mesenchymal tumor in the mediastinum: whole-exome sequencing reveals origin from pre-existing germ cell tumor

Author

Hirotake Fujii, Yosuke Yamada, Kentaro Yamamura, Yoshihiro Ishida, Marina Tsujimura, Kazuhisa Matsumoto, Satona Tanaka, Hiroshi Date, Tadaaki Nishikawa, Yukihiro Yoshida, Jumpei Kashima, Yasushi Yatabe, Seishi Ogawa, Alexander Marx, Thomas M. Ulbright, and Hironori Haga

Subjects
Adolescents and young adults, Yolk sac tumor, Mediastinum, Whole-genome doubling, Cell Biology, General Medicine, TP53, Vasculogenic mesenchymal tumor, Molecular Biology, Pathology and Forensic Medicine
Abstract

Vasculogenic mesenchymal tumor (VMT), a primitive mesenchymal neoplasm enriched by various-sized atypical vessels, is a new entity that develops in mediastinal germ cell tumors (GCTs) with yolk sac tumor (YST) components after chemotherapy. Notably, patients with VMT in the residual GCT have increased risk of developing sarcomas or hematopoietic malignancies. Here, we report a late-teenage male patient with residual teratoma and high-grade VMT after chemotherapy for a mediastinal mixed GCT, including YST. Whole-exome sequencing revealed biallelic inactivation of TP53 and extensive copy number alterations that suggested whole-genome doubling. The biopsy tissue of the mixed GCT before chemotherapy exhibited overlapping genetic alterations to those in the VMT. Immunohistochemical analyses of the VMT showed that the abnormal vessels were positive for cytokeratin, glypican 3, EZH2, and IMP3. The findings that VMT inherits the genetic alterations of pre-existing mixed GCT and exhibits a partly YST-like immunophenotype might contribute to its clinical aggressiveness.

Published
2023

4. Perception and preference of health care providers regarding protective role of immunity boosters against Covid -19

Author

Amruta Vishwas Dashputra, Nayse Jaydeep, Siddique R, Amit Date, and Quazi Shadama

Subjects
General Medicine
Abstract

Covid -19 caused by a virus to which the people with low immunity response are being affected. Immune boosters play a vital role in protecting human being from various infective organism. The immune boosters include vitamins, minerals, antioxidants, probiotics etc. Indian Government gave emphasis on improving immunity in March 2020. At That time many people started using immunity booster agents. : To study perception and preference of medical teachers about immunity booster agents against Covid -19. A questionnaire based cross sectional study was conducted among medical teachers. Questionnaire was framed in Google form and circulated in social media.Data was noted from excel sheet derived through google form and results were calculated in frequency and percentage, mean &SD. 78% participants were aware about immune boosting agents in initial period of Covid and highest used immune booster agent was Kadha (98%). Participant opined that source of information during this Covid period were Government & WHO guidelines (15%), TV/ newspaper (50%) and social media (41%). Most preferred and convenient to take immunity booster agent was fruits (67%). Reason for high search and use of immunity boosters is that in initial stage of Covid- 19 pandemic, there was theat to life especially in first and second wave of Covid. Along with immune boosters, diet, sleep, exercise and stress reduction are some of the most recommended measures. In present study highest used immune booster agent was Kadha. Allopathic, Ayurvedic and Homeopathic medicine were used as immunity booster agent.

Published
2023
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5. Utility of genome-wide DNA methylation profiling for pediatric-type diffuse gliomas

Author

Yoshihiro Otani, Kaishi Satomi, Yasuki Suruga, Joji Ishida, Kentaro Fujii, Koichi Ichimura, and Isao Date

Subjects
Genome-wide DNA methylation profiling, Cancer Research, Oncology, pediatric brain tumor, pediatric-type diffuse glioma, Neurology (clinical), General Medicine
Abstract

Despite the current progress of treatment, pediatric-type diffuse glioma is one of the most lethal primary malignant tumors in the central nervous system (CNS). Since pediatric-type CNS tumors are rare disease entities and highly heterogeneous, the diagnosis is challenging. An accurate diagnosis is essential for the choice of optimal treatment, which leads to precision oncology and improvement of the patient’s outcome. Genome-wide DNA methylation profiling recently emerged as one of the most important tools for the diagnosis of CNS tumors, and the utility of this novel assay has been reported in both pediatric and adult patients. In the current World Health Organization classification published in 2021, several new entities are recognized in pediatric-type diffuse gliomas, some of which require methylation profiling. In this review, we investigated the utility of genome-wide DNA methylation profiling in pediatric-type diffuse glioma, as well as issues in clinical application of this assay. Furthermore, the combination of genome-wide DNA methylation profiling and other comprehensive genomic assays, which may improve diagnostic accuracy and detection of the actionable target, will be discussed.

Published
2023
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6. Postoperative tegafur–uracil for stage I lung adenocarcinoma: first real-world data with an exploratory subgroup analysis

Author

Ryo, Miyata, Masatsugu, Hamaji, Akiyoshi, Nakakura, Satoshi, Morita, Yumeta, Shimazu, Masashi, Ishikawa, Hidenao, Kayawake, Toshi, Menju, Yasuto, Sakaguchi, Makoto, Sonobe, Mamoru, Takahashi, Akihiro, Aoyama, Ryota, Sumitomo, Cheng-Long, Huang, Tomoya, Kono, Ryo, Miyahara, Akira, Matsumoto, Hiromichi, Katakura, Takahisa, Fukada, Hiroaki, Sakai, Masashi, Kobayashi, Norihito, Okumura, Naoki, Date, Takuji, Fujinaga, Ei, Miyamoto, Tatsuo, Nakagawa, and Hiroshi, Date

Subjects
Surgery, General Medicine
Abstract

The effect of postoperative tegafur-uracil on overall survival (OS) after resection of stage I adenocarcinoma has been shown in clinical trials. The purpose of this study was to investigate whether findings from randomized trials of adjuvant tegafur-uracil are reproducible in a real-world setting.A retrospective cohort study was performed using a multi-institutional database that included all patients who underwent complete resection of pathological stage I adenocarcinoma between 2014 and 2016. Survival outcomes for patients managed with and without tegafur-uracil were analyzed using the Kaplan-Meier method and a Cox proportional hazards model for the whole patient cohort and in a selected cohort based on eligibility criteria of a previous randomized trial. Propensity score matching was used to adjust for confounding effects.After propensity score matching, the hazard ratios for OS were 0.57 (95% confidence interval (CI) 0.29-1.14, P = 0.11) in the whole cohort and 0.69 (95% CI 0.32-1.50, P = 0.35) in the selected cohort.The effects of tegafur-uracil in this retrospective study appear to be consistent with those found in randomized clinical trials. These effects may be maximized in patients aged from 45 to 75 years.

Published
2022
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12. Credit Card Fraud Detection Using Machine Learning

Author

Disha A. Date, Rugvedi Y. More, Rutuja P. Harne, and Mr. Dilip M. Dalgade

Subjects
General Medicine
Abstract

Credit card fraud has existed ever since credit cards were introduced, resulting in financial losses, identity theft, severe security threatas, and misuse of personal information. Such a situation already dire at an individual level only worsens when an organization gets involved. With the COVID-19 pandemic taking over the world and the introduction of quarantine, online transactions have surged exponentially. Naturally, credit cards have become one of the main means to process these transactions. With an extraordinary number of people making transactions every second, it becomes difficult to keep track of fraudulent ones. An increase in online transactions also increases the risk of cybercrimes, in this case, fraudulent transactions. In this paper, we proposed a fast yet light system to detect fraudulent transactions in the IEEE-CIS dataset. We used feature engineering and data mining techniques to analyze the dataset and make it usable for the model. Then, we fit the dataset to LightGBM and XGBoost to classify the transactions as fraud or non-fraud. Finally, we compared the performance of the two models. Since we were dealing with a heavily skewed dataset, we gauged the performance of our model with the F1 score and ROC AUC score. The obtained ROC AUC score was 95% for our proposed model.

Published
2022
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13. A case of chyluria with nephrotic-range proteinuria caused by lymphatic malformation, leading to a diagnosis of Klippel–Trenaunay syndrome

Author

Yuichiro Izumi, Ryosuke Date, Teruhiko Mizumoto, Terumasa Nakagawa, Yutaka Kakizoe, Masataka Adachi, Takashige Kuwabara, and Masashi Mukoyama

Subjects
Case Report, General Medicine
Abstract

Klippel-Trenaunay syndrome (KTS) is a rare syndrome, which is clinically diagnosed by the presence of unilateral limb hypertrophy with vascular malformation including cutaneous capillaries, veins and lymphatic vessels. Most cases typically exhibit cutaneous manifestations such as port-wine stains and limb hypertrophy from infancy, but cases with mild manifestations may remain undiagnosed. We here report a case of KTS who was diagnosed by chance chyluria. A 15-year-old girl who exhibited hematochyluria with nephrotic-range proteinuria was referred to our hospital. She had been diagnosed as idiopathic scoliosis accompanied by left lower limb hypertrophy in the past. She noticed her milky urine for the first time two months before. Immediately thereafter, she noticed edema of her left leg. Hematochyluria with nephrotic-range proteinuria was found by our initial urine examination. Magnetic resonance imaging suggested venous or lymphatic malformation along the left common iliac vein at the retroperitoneal side. Lymphoscintigraphy showed congestion of radioisotope around backside of the pancreas to the left renal hilus, suggesting an existence of lymphostasis. Based on the findings, we diagnosed the patient as KTS. After admission, hematochyluria and proteinuria were decreased and became insignificant by three days with bed rest. Her left leg edema was reduced. After taking a guidance to avoid intensive exercise, she was discharged in two weeks. Because the present case exhibited mild manifestations, diagnosis was made by urine abnormalities for the first time. The case suggests that we should be aware of the presence of undiagnosed patients of KTS due to relatively mild manifestations.

Published
2022
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14. Clinicopathological features of cytokeratin 5‐positive pulmonary adenocarcinoma

Author

K Terada, A Yoshizawa, S Sumiyoshi, M Rokutan‐Kurata, N Nakajima, M Hamaji, M Sonobe, T Menju, H Date, and H Haga

Subjects
Histology, General Medicine, Pathology and Forensic Medicine
Abstract

Cytokeratin 5 (CK5) is a marker for pulmonary squamous cell carcinoma; however, CK5 is sometimes present in pulmonary adenocarcinoma (ADC), and there is insufficient information regarding the clinicopathological features of CK5-positive ADC. We aimed to explore the clinicopathological characteristics of CK5-positive ADC using immunohistochemistry. We prepared the following two cohorts: a resected cohort containing 220 resected tumours for primarily studying the detailed morphological characteristics, and a tissue microarray (TMA) cohort containing 337 samples for investigating the associations of CK5 expression with other protein expressions, genetic and prognostic findings. CK5-positive ADC was defined to have ≥ 10% tumour cells and presence of CK5-positive tumour cells in the resected and TMA cohorts, respectively. CK5-positive ADCs were identified in 91 (16.3%) patients in the combined cohort. CK5-positive ADCs had male predominance (P = 0.012), smoking history (P = 0.001), higher stage (P 0.001), histological high-grade components (P 0.001), vascular invasion (P 0.001), mucinous differentiation (P 0.001), spread through airspaces (P 0.001), EGFR wild-type (P 0.001), KRAS mutations (P 0.001), ALK rearrangement (P 0.001) and ROS1 rearrangement (P = 0.002). In the resected cohort, more than half the CK5-positive ADCs (19 cases, 65.5%) showed mucinous differentiation; the remaining cases harboured high-grade components. In the TMA cohort, CK5-positive ADCs correlated with TTF-1 negativity (P = 0.002) and MUC5B, MUC5AC and HNF4alpha positivity (P 0.001, 0.048, 0.001). Further, CK5-positive ADCs had significantly lower disease-free and overall survival rates than CK5-negative ADCs (P 0.001 for each). Additionally, multivariate analysis revealed that CK5 expression was an independent poor prognostic factor. CK5-positive ADCs showed aggressive clinical behaviour, with high-grade morphology and mucinous differentiation.

Published
2022
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16. Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS

Author

Miller, Timothy M, Cudkowicz, Merit E, Andrews, Jinsy A, Hesters, Adele, Kermorvant, Hugo, Lacomblez, Lucette, Forestier, Nadine Le, Lenglet, Thimotée, Retail, Maryvonne, Ruiz Del Mar Amador, Maria, Salachas, François, Shotar, Eimad, Sourour, Nader, Babu, Suma, Dorst, Johannes, Froehlich, Elke, Fromm, Andrea, Kandler, Katharina, Langer, Eva, Leichtle, Sarah, Ludolph, Albert, Mayer, Kristina, Michels, Sebastian, Raubold, Sabine, Benatar, Michael, Schuster, Joachim, Weiland, Ulrike, Wiesenfarth, Maximilian, Witzel, Simon, Calvo, Andrea, Canosa, Antonio, Casale, Federico, Chiò, Adriano, Fuda, Giuseppe, Grassano, Maurizio, McDermott, Christopher J, Marchese, Giulia, Moglia, Cristina, Palumbo, Francesca, Salamone, Paolina, Ajiki, Takahiro, Akasaka, Aya, Ando, Masahiro, Arata, Hitoshi, Asuka, Kitamura, Baba, Kosuke, Cochrane, Thos, Bekku, Goichi, Chiba, Tomoya, Date, Yugaku, Eriko, Takeuchi, Hashiguchi, Akihiro, Hatatori, Ritsuko, Hayano, Eri, Hayashi, Yuto, Higashi, Keiko, Higuchi, Eriko, Chary, Sowmya, Hiramatsu, Yu, Horikawa, Rui, Ikenaka, Kensuke, Ishiura, Hiroyuki, Ito, Daisuke, Kawai, Sachiko, Kikuchi, Junko, Kuzuyama, Haruko, Li, Xuehong, Matsumoto, Chika, Chew, Sheena, Matsuura, Eiji, Michizono, Kumiko, Mitsui, Jun, Mitsutake, Akihiko, Mochizuki, Hideki, Nagamatsu, Akemi, Nagano, Seiichi, Nakamura, Tomonori, Naruse, Hiroya, Ogasawara, Asuka, Zhu, Han, Okada, Kensuke, Okamoto, Yuji, Okuno, Tatsusada, Oyama, Satoshi, Ozono, Tatsuhiko, Sakiyama, Yusuke, Sakuishi, Kaori, Seki, Morinobu, Shibata, Shota, Shimizu, Mikito, Wu, Fan, Takahata, Katsunori, Takahito, Yoshizaki, Takashima, Hiroshi, Takeichi, Hiroko, Tashiro, Yuichi, Toda, Tatsushi, Tomizu, Yuki, Tomoya, Wadayama, Ujiakira, Nishiike, Yashita, Daiki, Nestorov, Ivan, Al-Chalabi, Ammar, Alix, James, Bangalore, Priyadarshini, Blackburn, Daniel, Chiwera, Theresa, Clegg, Rosie, Collins, Alexis, Cooper-Knock, Jonathan, Emery, Anna, Franklin, John, Genge, Angela, Graham, Danielle, Green, Louisa, Harvey, Callum, Hobson, Esther, Islam, Mahjabim, Jenkins, Thomas Michael, Kazoka, Mbombe, Kelly, Gillian, Korley, Mercy, Madarshahaian, Daniel, Mayl, Keith, Sun, Peng, McDermott, Christopher John, Radford, Alex, Shaw, Christopher, Shaw, Pamela J, Sidebottom, Joe, Smart, Lynne, Sreedharan, Jemeen, Stone, Ben, Tsironis, Theocharis, Tuddenham, Lee, McNeill, Manjit, Verber, Nick, Wollff, Helen, Young, Stacy, Zis, Panagiotis, Adamo, Ashley, Ahmed, Arubah, Ajroud-Driss, Senda, Alameda, Gustave, Arcila-Londono, Ximena, Fanning, Laura, Baird, Candy, Bazan, Tracy, Berry, James, Bordeau, Jane, Bradford, Wendy, Brook, Nyda, Brown, Lauren, Bucelli, Robert C, Ferguson, Toby A, Buckner, Katherine, Budler, Michael W, Burba, Lindita, Burke, Katherine, Calhoun, Ashley D, Campbell, Sarah, Carey, Judith, Caristo, Irys B, Carty, Simon, Chan, Emmanuel, Fradette, Stephanie, Chaudhry, Vinay, Chen, Ricky, Chow, Saephanh, Clawson, Lora L, Clemens, Mitchell, Cloninger, Suzann E, Coleman-Wood, Krista, Cooper, Thomas N, Cummings, Arlena, Daniels, Jacquelyn, VALOR, DeSaro, Pamela, DeWitt, Michelle, Dedi, Brixhilda, Dempsey, Debbie, Denny, Carol, Doherty, Jenna, Doherty, Leana, Donahue, Megan, Doyle, Michael, Duncan, Jessie, Group, OLE Working, Elman, Lauren, Eloge, Christine M, Echiti, Desirae R, Ferrey, Dominic, Fournier, Christina, Fukumura, Yuriko, Gallagher, Katherine, Garaycoa, Jessica, Garrett, Mark, Gibson, Richard L, Beullens, Lien, Gifford, Ryan, Glass, Jonathan D, Gogol, Danuta, Golden, Shea, Gonzalez, Alexa, Goodman, Ira, Goolsby, Christopher, Goslin, Kimberly, Goulbourne, Michael, Granit, Volkan, Claeys, Kristl, Grignon, Anne-Laure, GuhaRay, Adreeja, Guide, Debra, Gundogdu, Melek Betul, Gutierrez, Gil, Hastings, Debbie, Hayzen, Colleen, Herzog, Hilary, Holloway, Raegan, Jacobs, Gabriel, Claeys, Thomas, Jacobsen, Bill, James, Virginia, Jenkins, Liberty, Jockel-Balsarotti, Jennifer, Johnson, Linda Carol, Jose, Sunil, Joslin, Benjamin, Karanja, Elizabeth, Katz, Jonathan, Keener, Anthony, Couwelier, Goedele, Kittle, Gale, Klein, Sara, Kreple, Collin, Rebecca, Rebecca, Kuenzler, Kuenzler, Kusnir, Jorge, Labbe, Kristen, Lachica-Encinas, Nicolet, Ladha, Shafeeq, Leimer, Lesli, D'Hondt, Ann, Levy, Michael, Levy, Wendy, Li, Yingji, Likanje, Marie-France, Livigni, Rebecca, Locatelli, Eduardo, Luppino, Sarah, Malcolm, Amber, Maragakis, Nicholas, Marin, Horia, Debien, Elisa, Markowitz, Clyde, Markway, Jesse, McCaffrey, Alexandra, McCoy, Arita, McCoy Gross, Kelly, Mehta, Kush, Meyer, Robert, Milan, Jennifer, Miller, Timothy, Miller, Robert G, de Keersmaecker, Sebastiaan, Morales, Francisco, Mosmiller, Elizabeth, Mott, Donovan, Moulton, Kelsey, Murphy, Christine A, Negron, Tirso, Nelson, Cassandra, Newman, Daniel S, Nissinen, Janne Kristoffer, Norman, Andrew, Della Faille, Laetitia, Ohkubo, Takuya, Olney, Nicholas, Ortiz, Natasha, Oskarsson, Bjorn, Pace, Mitchell, Packard, Kathleen, Padgett, Denny, Paganoni, Sabrina, Paredes, Maria E, Parker, Elizabeth, Delmotte, Koen, Partlow, Ann, Pattee, Gary L, Paulett, Jany, Pelot, Antoinette, Pfeifer, Kyle M, Pijanowski, Olivia, Pioro, Erik, Polak, Meraida, Prakash, Ahalya, Previte, Rosemarie, Depoortere, Sofie, Pukenas, Bryan, Quinn, Colin, Ravits, John, Razavi, Ryan, Regan, Tyler, Riley, Kristen M, Roth, Heather, Sanders, Danica, Scalia, Jennifer, Schmidt, Emma, de Velder, Laura, Schwen, Edward, Shah, Jaimin, Shah, Stuti, Shefner, Jeremy, Sheldon, Danielle, Simmons, Karon, Singh, Navneet K, Singleton, Jessica, Smiley, Richard, Smith, William B, Dobbels, Laurens, Smith, Sean, Sotirchos, Elias, Sorenson, Eric, Staff, Nathan, Steele, Julie, Steijlen, Kara, Stirrat, Taylor, Stoica, George S, Strong, Stephanie, Sufit, Robert, Sobue, Gen, Gijs, Jeroen, Sultze, Jane, Swartz, Amy, Szymanski, April, Tay, Anna, Thakore, Nimish, Thiessen, Diana, Thotala, Sukrutha, Trudell, Randall G, Turcotte, Nicole, Turner, Michelle, Horckmans, Simon, Uchil, Alpa, Upadhyay, Vihar, Usman, Uzma, Vallis, Anne, Vaporean-Bussey, Danielle, Vladimirova, Valentine, Weber, Harli, Winbigler, Jennifer, Wojanowski, Heather, Wulf, Charlie, Lamaire, Nikita, Yasek, Julia, Yoo, Stephanie, Zivalic, Hannah, Cole, Alexandra, File, Greta, Foate, Jeremy, Mason, Deborah, Newton, Susan, Roberts, Stephen, Sellwood, Cory Dean, Liessens, Hannelore, Swan, James, Werno, Anja, Zhong, Cathy, Masrori, Pegah, Nysten, Celine, Schotte, Caroline, Serrien, Anouk, Swinnen, Bart, Tilkin, Petra, van Daele, Sien, Van Damme, Philip, Vynckier, Jan, Wouters, Anke, Abrahao, Agessandro, Angle, Mark, Badawy, Mohamed, Berube, Maxime, Bertone, Vanessa, Cooper, Sarah Marie, Dobrowolski, Peter, Fong, Helen, Hannouche, Matthew, Hartley, Denise, Hogan, Michael, Johnston, Wendy, Khalfallah, Yousra, Korngut, Lawrence, Kroetsch, Gina, Letourneau, Justin, Magnussen, Claire, Martinez, Jose, Massie, Rami, Mobach, Theodore, Mookshah, Jahan, Ozelsel, Timur, Parks, Andrea, Petrillo, Janet, Pfeffer, Gerald, Ludolph, Albert C, Pham, Shirley, Phung, Liane, Shiungsun, Rodney, Pi-Shan, Li, Santos, Denizart, Salmon, Kristiana, Saunders, Natalie, Sembinelli, Dylan, Tymkow, Kelsey, Wong, Berchman, Zinman, Lorne, Karlsborg, Merete, Pedersen Lomholt, Therese, Nilsson, Sigrid, Salvesen, Lisette, Skov, Pernille, Svenstrup, Kristen, Bruneteau, Gaelle, Calerencon, Frederic, and Guimaraes Costa, Raquel

Subjects
Adult, drug effects [Recovery of Function], Spinal, Oligonucleotides, blood [Neurofilament Proteins], administration & dosage [Oligonucleotides, Antisense], tofersen, Injections, blood [Amyotrophic Lateral Sclerosis], pharmacology [Oligonucleotides, Antisense], Superoxide Dismutase-1, Double-Blind Method, Neurofilament Proteins, Humans, ddc:610, Antisense, Injections, Spinal, Biomarkers, Recovery of Function, Amyotrophic Lateral Sclerosis, Oligonucleotides, Antisense, blood [Biomarkers], drug therapy [Amyotrophic Lateral Sclerosis], therapeutic use [Oligonucleotides, Antisense], SOD1 protein, human, General Medicine, genetics [Superoxide Dismutase-1], genetics [Amyotrophic Lateral Sclerosis], cerebrospinal fluid [Biomarkers], cerebrospinal fluid [Superoxide Dismutase-1], cerebrospinal fluid [Amyotrophic Lateral Sclerosis]
Abstract

The intrathecally administered antisense oligonucleotide tofersen reduces synthesis of the superoxide dismutase 1 (SOD1) protein and is being studied in patients with amyotrophic lateral sclerosis (ALS) associated with mutations in SOD1 (SOD1 ALS).In this phase 3 trial, we randomly assigned adults with SOD1 ALS in a 2:1 ratio to receive eight doses of tofersen (100 mg) or placebo over a period of 24 weeks. The primary end point was the change from baseline to week 28 in the total score on the ALS Functional Rating Scale-Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) among participants predicted to have faster-progressing disease. Secondary end points included changes in the total concentration of SOD1 protein in cerebrospinal fluid (CSF), in the concentration of neurofilament light chains in plasma, in slow vital capacity, and in handheld dynamometry in 16 muscles. A combined analysis of the randomized component of the trial and its open-label extension at 52 weeks compared the results in participants who started tofersen at trial entry (early-start cohort) with those in participants who switched from placebo to the drug at week 28 (delayed-start cohort).A total of 72 participants received tofersen (39 predicted to have faster progression), and 36 received placebo (21 predicted to have faster progression). Tofersen led to greater reductions in concentrations of SOD1 in CSF and of neurofilament light chains in plasma than placebo. In the faster-progression subgroup (primary analysis), the change to week 28 in the ALSFRS-R score was -6.98 with tofersen and -8.14 with placebo (difference, 1.2 points; 95% confidence interval [CI], -3.2 to 5.5; P = 0.97). Results for secondary clinical end points did not differ significantly between the two groups. A total of 95 participants (88%) entered the open-label extension. At 52 weeks, the change in the ALSFRS-R score was -6.0 in the early-start cohort and -9.5 in the delayed-start cohort (difference, 3.5 points; 95% CI, 0.4 to 6.7); non-multiplicity-adjusted differences favoring early-start tofersen were seen for other end points. Lumbar puncture-related adverse events were common. Neurologic serious adverse events occurred in 7% of tofersen recipients.In persons with SOD1 ALS, tofersen reduced concentrations of SOD1 in CSF and of neurofilament light chains in plasma over 28 weeks but did not improve clinical end points and was associated with adverse events. The potential effects of earlier as compared with delayed initiation of tofersen are being further evaluated in the extension phase. (Funded by Biogen; VALOR and OLE ClinicalTrials.gov numbers, NCT02623699 and NCT03070119; EudraCT numbers, 2015-004098-33 and 2016-003225-41.).

Published
2022
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18. Preliminary study of the safety of acrinol in probe‐based confocal laser endomicroscopy during transurethral resection of bladder tumors

Author

Yoshio Naya, Natsuki Takaha, Iseei Hayashi, Masaru Mori, Seiki Date, and Osamu Ukimura

Subjects
Carcinoma, Transitional Cell, Microscopy, Confocal, Urinary Bladder Neoplasms, Lasers, Humans, Cystoscopy, General Medicine, Ethacridine, Transurethral Resection of Bladder
Abstract

We previously reported that probe-based confocal laser endomicroscopy using acrinol can depict cancerous nuclei. The objective of this study was to confirm the safety of acrinol in patients. For all seven patients, '50 ml' of a 0.1% acrinol and '1 ml' of 10% fluorescein in 99 ml of normal saline were introduced into the bladder. The laser probe adhered to the suspicious lesion from the working channel of the cystoscope. The patients underwent mucosal biopsy and transurethral resection after observation. Adverse events were noted during a valuation using common terminology criteria for adverse events version 4.0. Confocal laser endomicroscopy detected the nuclei of cancer cells in all seven patients. No adverse event was observed in any of the seven patients. Confocal laser endomicroscopy using acrinol as a novel dye can help visualize the cancerous nuclei of bladder urothelial carcinoma during cystoscopy without severe adverse events.

Published
2022
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19. Trigeminal neuralgia caused by a persistent primitive trigeminal artery: preoperative three-dimensional multifusion imaging and computational fluid dynamics analysis. Illustrative case

Author

Toru Satoh, Takao Yasuhara, Michiari Umakoshi, and Isao Date

Subjects
General Medicine
Abstract

BACKGROUND Trigeminal neuralgia (TN) is caused by trigeminal nerve compression by colliding vessels. Preoperative three-dimensional (3D) multifusion images are useful for surgical simulations. Moreover, computational fluid dynamics (CFD) analysis of colliding vessels may be useful for hemodynamic evaluation at the site of neurovascular contact (NVC). OBSERVATIONS A 71-year-old woman had TN due to compression of the trigeminal nerve by the superior cerebellar artery (SCA) fused with the persistent primitive trigeminal artery (PTA). Preoperative 3D multifusion simulation images of silent magnetic resonance (MR) angiography and MR cisternography depicted the NVC, including the trigeminal nerve, SCA, and PTA. CFD analysis revealed the hemodynamic condition of the NVC, including the SCA and PTA. The wall shear stress magnitude (WSSm) at the NVC showed a local elevation due to flow confluence from the SCA and PTA. High WSSm was observed in the NVC. LESSONS Preoperative simulation images of MR angiography and MR cisternography may depict the NVC. CFD analysis can provide the hemodynamic condition at the NVC.

Published
2023
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20. Development of novel layered polyglycolic acid sheet for regeneration of critical-size defect in rat trachea

Author

Yoshitake Murata, Yojiro Yutaka, Rieko Hirata, Yu Hidaka, Masatsugu Hamaji, Akihiro Yoshizawa, Yo Kishimoto, Koichi Omori, and Hiroshi Date

Subjects
Pulmonary and Respiratory Medicine, Surgery, General Medicine, Cardiology and Cardiovascular Medicine
Abstract

OBJECTIVES Polyglycolic acid (PGA) sheets are difficult to adapt to the central airway because of poor durability against high air pressure. Therefore, we developed a novel layered PGA material to cover the central airway and examined its morphologic traits and functional performance as a potential tracheal replacement. METHODS A critical-size defect in rat cervical tracheas was covered with the material. Morphologic changes were bronchoscopically and pathologically evaluated. Functional performance was evaluated by regenerated ciliary area, ciliary beat frequency and ciliary transport function determined by measuring the moving distance of microspheres dropped onto the trachea (µm/s). The evaluation time points were 2 weeks, 1 month, 2 months and 6 months after surgery (n = 5, respectively). RESULTS Forty rats underwent implantation, and all survived. Histological examination confirmed ciliated epithelization on the luminal surface after 2 weeks. Neovascularization was observed after 1 month, tracheal glands after 2 months and chondrocyte regeneration after 6 months. Although the material was gradually replaced by self-organization, tracheomalacia was not bronchoscopically observed at any time point. The area of regenerated cilia significantly increased between 2 weeks and 1 month (12.0% vs 30.0%; P = 0.0216). The median ciliary beat frequency significantly improved between 2 weeks and 6 months (7.12 vs 10.04 Hz; P = 0.0122). The median ciliary transport function was significantly improved between 2 weeks and 2 months (5.16 vs 13.49 µm/s; P = 0.0216). CONCLUSIONS The novel PGA material showed excellent biocompatibility and tracheal regeneration both morphologically and functionally 6 months after tracheal implantation.

Published
2023
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21. Prognostic factors for lung transplant recipients focusing on age and gender: the Japanese lung transplantation report 2022

Author

Hisashi Oishi, Yoshinori Okada, Masaaki Sato, Jun Nakajima, Daisuke Nakajima, Takeshi Shiraishi, Toshihiko Sato, Takashi Kanou, Yasushi Shintani, Kentaroh Miyoshi, Shinichi Toyooka, Sumiko Maeda, Masayuki Chida, Keitaro Matsumoto, Takeshi Nagayasu, Hidemi Suzuki, Ichiro Yoshino, Yasushi Matsuda, Yasushi Hoshikawa, and Hiroshi Date

Subjects
Surgery, General Medicine
Abstract

Purpose To clarify the impact of donor and recipient characteristics on the survival of recipients before and after lung transplantation in the Japanese population. Methods Patients’ data were collected for retrospective analysis from all authorized lung transplant centers in Japan. We included 1963 patients listed for lung transplantation by the end of December 2021, comprised of 658 deceased-donor and 270 living-donor lung transplants. Results Primary disease had a significant impact on the mortality of patients waiting for transplantation. The indications for transplant significantly affected the post-transplant survival rate of deceased-donor lung transplant recipients. The recipient’s age also significantly affected the post-transplant survival rate of the deceased-donor and living-donor lung transplant recipients. The recipients of grafts transplanted from donors aged 61 years or older showed a worse post-transplant survival rate (≧60 years old). The survival rate for the combination of a female donor to a male recipient among the deceased-donor lung transplant recipients was the worst among the four combinations. Conclusion The donor and recipient characteristics significantly impacted the survival of recipients after lung transplantation. The underlying mechanism of the negative impact of the gender mismatch of female donor to male recipient on post-transplant survival needs to be investigated further.

Published
2023
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22. Robot-assisted segmentectomy for small lung cancer using a radiofrequency identification marker

Author

Akihiro Ohsumi, Yojiro Yutaka, and Hiroshi Date

Subjects
Pulmonary and Respiratory Medicine, Surgery, General Medicine, Cardiology and Cardiovascular Medicine
Abstract

Owing to the prevalence of robot-assisted thoracoscopic surgery and the increase in the number of small lung cancer cases, robot-assisted thoracoscopic segmentectomy cases have also been increasing. For small lung cancers, such as ground-glass opacity lesions, identifying the location and securing a sufficient free margin from the main tumor can be difficult. We have already developed and reported the clinical application of a new marking system, a radiofrequency identification marker. In the current study, we applied this technique to robot-assisted thoracoscopic segmentectomies. Concomitant with other devices, we believe that robot-assisted thoracoscopic surgery has a great advantage in segmentectomy.

Published
2022
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23. Fissure-last technique for left upper lobe lung cancer with interlobar invasion: how to do it?

Author

Yojiro Yutaka, Satona Tanaka, Yoshito Yamada, Akihiro Ohsumi, Daisuke Nakajima, Masatsugu Hamaji, Toshi Menju, and Hiroshi Date

Subjects
Pulmonary and Respiratory Medicine, Lung Neoplasms, Thoracic Surgery, Video-Assisted, Humans, Surgery, General Medicine, Pulmonary Artery, Pneumonectomy, Cardiology and Cardiovascular Medicine, Lung
Abstract

The fissure-last technique is used to minimize postoperative air leak after anatomical lung resection when the interlobar pulmonary artery is inaccessible through the fused fissure. After first dividing the hilar bronchovascular structures, the incomplete fissure is divided using staplers. This technique can be applied for lobectomy combined with segmentectomy in lung cancer with interlobar invasion. We performed this thoracoscopic fissure-last technique in a lung cancer patient in the left upper lobe with invasion to the superior segment (S6) in the left lower lobe.

Published
2022
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24. Patients on Buprenorphine Formulations Undergoing Surgery

Author

Katelynn Champagne, Preshita Date, Juan Pablo Forero, Joshua Arany, and Karina Gritsenko

Subjects
Analgesics, Opioid, Pain, Postoperative, Anesthesiology and Pain Medicine, Humans, Pain, Pain Management, Neurology (clinical), General Medicine, Analgesia, Buprenorphine
Abstract

To review the pharmacology of buprenorphine, the evolution of buprenorphine dosing recommendations, and the current literature regarding its recommendations for the perioperative period.There is a consensus that for all surgeries, buprenorphine should be continued throughout the perioperative period. If the surgery is a minimal to mild pain surgery, no dose adjustment is needed. There is no clear consensus regarding moderate to severe pain. With all surgeries, multimodal analgesia should be utilized, with regional anesthesia when possible. Patients taking buprenorphine should continue their buprenorphine perioperatively; whether to decrease or maintain dosing is up for debate. Multimodal analgesia should also be used throughout the perioperative period, and communication between the patient and all provider teams is of the utmost importance to provide adequate analgesia during the perioperative period, as well as to arrange safe analgesia upon discharge.

Published
2022
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25. Incidence and clinical characteristics of spinal arteriovenous shunts: hospital-based surveillance in Okayama, Japan

Author

Masafumi Hiramatsu, Koji Tokunaga, Etsuji Suzuki, Yu Takahashi, Satoshi Murai, Ryota Ishibashi, Shunji Matsubara, Yoko Yamaoka, Isao Date, Masaki Chin, Yuko Miyazaki, Hiroki Takai, Jun Haruma, Takao Yasuhara, Masaaki Uno, Tomohito Hishikawa, Kazuhiko Nishi, Yuji Takasugi, and Kenji Sugiu

Subjects
Central Nervous System Vascular Malformations, Epidural Space, Male, medicine.medical_specialty, business.industry, Vascular disease, Incidence, Incidence (epidemiology), Arteriovenous fistula, Arteriovenous malformation, General Medicine, Hospital based, medicine.disease, Spinal cord, Magnetic Resonance Imaging, Hospitals, Surgery, Spinal epidural, medicine.anatomical_structure, Japan, Spinal Cord, Epidemiology, medicine, Humans, business
Abstract

OBJECTIVE There have been no accurate surveillance data regarding the incidence rate of spinal arteriovenous shunts (SAVSs). Here, the authors investigate the epidemiology and clinical characteristics of SAVSs. METHODS The authors conducted multicenter hospital-based surveillance as an inventory survey at 8 core hospitals in Okayama Prefecture between April 1, 2009, and March 31, 2019. Consecutive patients who lived in Okayama and were diagnosed with SAVSs on angiographic studies were enrolled. The clinical characteristics and the incidence rates of each form of SAVS and the differences between SAVSs at different spinal levels were analyzed. RESULTS The authors identified a total of 45 patients with SAVSs, including 2 cases of spinal arteriovenous malformation, 5 cases of perimedullary arteriovenous fistula (AVF), 31 cases of spinal dural AVF (SDAVF), and 7 cases of spinal epidural AVF (SEAVF). The crude incidence rate was 0.234 per 100,000 person-years for all SAVSs including those at the craniocervical junction (CCJ) level. The incidence rate of SDAVF and SEAVF combined increased with advancing age in men only. In a comparative analysis between upper and lower spinal SDAVF/SEAVF, hemorrhage occurred in 7/14 cases (50%) at the CCJ/cervical level and in 0/24 cases (0%) at the thoracolumbar level (p = 0.0003). Venous congestion appeared in 1/14 cases (7%) at the CCJ/cervical level and in 23/24 cases (96%) at the thoracolumbar level (p < 0.0001). CONCLUSIONS The authors reported detailed incidence rates of SAVSs in Japan. There were some differences in clinical characteristics of SAVSs in the upper spinal levels and those in the lower spinal levels.

Published
2022
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26. Evaluation of the Prediction and Durability on the Chloride Penetration in Cementitious Materials with Blast Furnace Slag as Cement Addition

Author

Prang Subpa-asa, Nobukazu Nito, Satoshi Fujiwara, and Shigeyuki Date

Subjects
effective diffusion coefficient, blast furnace slag, chloride ion penetration, chloride prediction, General Medicine
Abstract

Blast furnace slag (BFS) is a mortar additive in which the utilization of varied curing conditions and the basicity of BFS determine the fineness of the resulting mortar and, thereby, its salt prevention properties. This study evaluates and compares the salt-prevention properties of mortar prepared by either steam curing or water curing. The physical properties, for example, the BFS fineness, revealed the factors significantly affected by basicity that influence the salt-preventive properties of mortar in the specimens examined, such as the lead time and diffusion coefficient. Furthermore, these factors were also significantly affected by differences in curing conditions and other physical properties. However, few studies have examined its use in reducing chloride ion permeability as the main factor of corrosion reactions. Thus, this study evaluates specific surface, water/binder ratio (W/B), and curing conditions on the chloride penetration in cementitious materials with blast furnace slag as cement addition in terms of delaying chloride ion penetration, which affects corrosion reactions. Results of the study are intended to guide development of products for use in the precast concrete industry, toward extending the life of concrete structures, especially reinforced concrete structures in marine environments. In addition, the resulting durability measurements from the experiment conducted are illustrated. This study indicates that differences in Blaine size properties significantly influence water curing. Furthermore, results reveal the effects of combining BFS with various Blaine values and ratio-affecting properties on mortar. In conclusion, concrete materials that decrease durability against chloride attack and improve mechanical properties for precast manufacturer industrial applications are successfully developed in this study. In addition, the use of water-curing conditions, high Blaine value, high cement replacement ratio, and W/B tend to improve the general mechanical property performance and durability against chloride ion attack.

Published
2022
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27. Nationwide registry for patients with neuroendocrine neoplasm of pancreas, gastrointestinal tract, lungs, bronchi, or thymus in Japan

Author

Toshihiko, Masui, Tetsuhide, Ito, Izumi, Komoto, Shinsuke, Kojima, Yosuke, Kasai, Minoru, Tanabe, Kazuo, Hara, Satoshi, Hirano, Takuji, Okusaka, Yasushi, Ichikawa, Yusuke, Kinugasa, Norihiro, Kokudo, Atsushi, Kudo, Akihiro, Sakurai, Kenichi, Sugihara, Hiroshi, Date, Ken, Haruma, Susumu, Hijioka, Koichi, Hirata, Hiroo, Yamano, Motohiro, Sakamine, Takashi, Kikuchi, Masanori, Fukushima, Masayuki, Imamura, and Shinji, Uemoto

Subjects
Bronchi, Hematology, General Medicine, Prognosis, Cohort Studies, Pancreatic Neoplasms, Neuroendocrine Tumors, Japan, Oncology, Lymphatic Metastasis, Humans, Surgery, Registries, Pancreas, Gastrointestinal Neoplasms, Retrospective Studies
Abstract

Background Neuroendocrine neoplasm (NEN) is a comparatively rare tumor that has been considered indolent. Due to these characteristics, detailed epidemiological data have not been analyzed in Japan. To elucidate the present status of NEN diagnosis and treatment in Japan, we started a registry cohort study in January 2015. Methods Patients pathologically diagnosed with NENs of the pancreas, gastrointestinal tract, lungs, bronchi, or thymus after January 2012 were enrolled in this registry after the date of ethics review committee approval in each hospital or institute. Follow-up was continued for enrolled patients. Results During 5 years of enrollment between January 2015 and December 2019, a total of 1526 participants from 63 departments were enrolled in this registry (mean, 305.2 participants/year), covering approximately 5.8% of the annual incidence of NENs in Japan. For pancreatic NEN, 41.9% of patients had metastasis and the dominant metastatic site was the liver, at twice the rate of lymph node metastasis in the current registry. In contrast, the frequency of lymph node metastasis from gastrointestinal (GI)-NEN was similar to that of the liver. The distribution of WHO 2019-based grades varied according to the primary site. Low-to-intermediate grade (G1–G2) was dominant for duodenal, jejunal/ileal, rectal, and pancreatic NENs, whereas high grade (G3 or NEC) was dominant for esophageal, stomach, and colon NENs. For PanNENs, G3 and NEC accounted only for 1.6% and 2.9%, respectively. Conclusions These cohort data provide crucial information for clinical research to clarify the characteristics of NENs in Japan.

Published
2022
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28. Successful lung transplant cases with ex vivo lung perfusion assessment of extended criteria donor lungs

Author

Daisuke Nakajima, Shunichi Nagata, Hidenao Kayawake, Satona Tanaka, Yoshito Yamada, Yojiro Yutaka, Akihiro Ohsumi, Masatsugu Hamaji, Toyofumi F. Chen-Yoshikawa, and Hiroshi Date

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, Extracorporeal Circulation, General Medicine, Middle Aged, Tissue Donors, Perfusion, Humans, Female, Surgery, Cardiology and Cardiovascular Medicine, Lung, Lung Transplantation
Abstract

We report our successful experience in two lung transplant cases in which ex vivo lung perfusion (EVLP) was used to evaluate the function of injured brain-dead donor lungs that were otherwise initially unacceptable. After the donor's lungs were declined for transplantation by all other transplant centers, the lungs were offered to the patients listed for lung transplantation in our hospital. The donor lung function was considered acceptable for transplantation after the 3-h EVLP assessment. In the first case, a 32-year-old man with bronchiolitis obliterans after hematopoietic stem cell transplantation underwent hybrid lung transplantation, that was right brain-dead donor lung transplantation, combined with native-upper lobe sparing living-donor lobar lung transplantation on the left side. In the second case, a 61-year-old woman received the right single lung transplantation for idiopathic pulmonary fibrosis. Both patients are doing well at one and a half years after lung transplantation.

Published
2022
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34. Comparison of living-donor lobar lung transplantation and cadaveric lung transplantation for pulmonary hypertension

Author

Hidenao Kayawake, Satona Tanaka, Yoshito Yamada, Shiro Baba, Hideyuki Kinoshita, Kazuhiro Yamazaki, Tadashi Ikeda, Kenji Minatoya, Yojiro Yutaka, Masatsugu Hamaji, Akihiro Ohsumi, Daisuke Nakajima, and Hiroshi Date

Subjects
Pulmonary and Respiratory Medicine, Surgery, General Medicine, Cardiology and Cardiovascular Medicine
Abstract

OBJECTIVES Living-donor lobar lung transplantation (LDLLT) is a life-saving procedure for critically ill patients with various lung diseases, including pulmonary hypertension (PH). However, there are concerns regarding the development of heart failure with pulmonary oedema after LDLLT in which only 1 or 2 lobes are implanted. This study aimed to compare the preoperative conditions and postoperative outcomes of LDLLT with those of cadaveric lung transplantation (CLT) in PH patients. METHODS Between 2008 and 2021, 34 lung transplants for PH, including 12 LDLLTs (5 single and 7 bilateral) and 22 bilateral CLTs, were performed. Preoperative variables and postoperative outcomes were retrospectively compared between the 2 procedures. RESULTS Based on the preoperative variables of less ambulatory ability (41.7% vs 100%, P 0.99, respectively). Furthermore, the 5-year overall survival rate was similar between the 2 groups (90.0% vs 76.3%, P = 0.489). CONCLUSIONS Although LDLLT patients with PH had worse preoperative conditions and received smaller grafts than CLT patients, LDLLT patients demonstrated similar perioperative outcomes and prognoses as CLT patients. LDLLT is a viable treatment option for patients with PH.

Published
2023
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35. Cover Image

Author

K Terada, A Yoshizawa, S Sumiyoshi, M Rokutan‐Kurata, N Nakajima, M Hamaji, M Sonobe, T Menju, H Date, and H Haga

Subjects
Histology, General Medicine, Pathology and Forensic Medicine
Published
2023
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36. An Analytical Method for Quantifying the Yields of DNA Double-Strand Breaks Coupled with Strand Breaks by γ-H2AX Focus Formation Assay Based on Track-Structure Simulation

Author

Yoshie Yachi, Yusuke Matsuya, Yuji Yoshii, Hisanori Fukunaga, Hiroyuki Date, and Takeshi Kai

Subjects
Monte Carlo track-structure simulation, photon irradiation, gamma-H2AX focus formation assay, Organic Chemistry, complex DSB, γ-H2AX focus formation assay, General Medicine, Catalysis, Computer Science Applications, Inorganic Chemistry, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy
Abstract

Complex DNA double-strand break (DSB), which is defined as a DSB coupled with additional strand breaks within 10 bp in this study, induced after ionizing radiation or X-rays, is recognized as fatal damage which can induce cell death with a certain probability. In general, a DSB site inside the nucleus of live cells can be experimentally detected using the γ-H2AX focus formation assay. DSB complexity is believed to be detected by analyzing the focus size using such an assay. However, the relationship between focus size and DSB complexity remains uncertain. In this study, using Monte Carlo (MC) track-structure simulation codes, i.e., an in-house WLTrack code and a Particle and Heavy Ion Transport code System (PHITS), we developed an analytical method for qualifying the DSB complexity induced by photon irradiation from the microscopic image of γ-H2AX foci. First, assuming that events (i.e., ionization and excitation) potentially induce DNA strand breaks, we scored the number of events in a water cube (5.03 × 5.03 × 5.03 nm3) along electron tracks. Second, we obtained the relationship between the number of events and the foci size experimentally measured by the γ-H2AX focus formation assay. Third, using this relationship, we evaluated the degree of DSB complexity induced after photon irradiation for various X-ray spectra using the foci size, and the experimental DSB complexity was compared to the results estimated by the well-verified DNA damage estimation model in the PHITS code. The number of events in a water cube was found to be proportional to foci size, suggesting that the number of events intrinsically related to DSB complexity at the DNA scale. The developed method was applicable to focus data measured for various X-ray spectral situations (i.e., diagnostic kV X-rays and therapeutic MV X-rays). This method would contribute to a precise understanding of the early biological impacts of photon irradiation by means of the γ-H2AX focus formation assay.

Published
2023
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37. Epidermal growth factor receptor tyrosine kinase inhibitors as first-line treatment for postoperative recurrent EGFR-mutated lung adenocarcinoma: a multi-institutional retrospective study

Author

Ryo Miyata, Masatsugu Hamaji, Atsushi Kawaguchi, Yumeta Shimazu, Masaki Ikeda, Masashi Ishikawa, Hidenao Kayawake, Toshi Menju, Masashi Kobayashi, Norihito Okumura, Yasuto Sakaguchi, Makoto Sonobe, Akira Matsumoto, Tsuyoshi Shoji, Hiromichi Katakura, Ryota Sumitomo, Cheng-Long Huang, Mamoru Takahashi, Akihiro Aoyama, Yusuke Muranishi, Tomoya Kono, Ryo Miyahara, Naoki Date, Takuji Fujinaga, Ei Miyamoto, Tatsuo Nakagawa, Takahisa Fukada, Hiroaki Sakai, and Hiroshi Date

Subjects
Pulmonary and Respiratory Medicine, ErbB Receptors, Lung Neoplasms, Mutation, Humans, Surgery, Adenocarcinoma of Lung, General Medicine, Neoplasm Recurrence, Local, Cardiology and Cardiovascular Medicine, Prognosis, Protein Kinase Inhibitors, Retrospective Studies
Abstract

OBJECTIVES The aim of this study was to analyse the long-term survival outcomes and prognostic factors of patients receiving epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as first-line treatment for postoperative recurrent EGFR-mutated lung adenocarcinoma. METHODS Using a multi-institutional database, we performed a retrospective chart review to identify all patients who had undergone complete resection of stage I–III EGFR-mutated lung adenocarcinoma at 11 acute care hospitals between 2009 and 2016 and had received first-line EGFR-TKI treatment for postoperative recurrence. Adverse events, progression-free survival (PFS) and overall survival (OS) were investigated. Survival outcomes were assessed using Kaplan–Meier analysis. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for PFS and OS. RESULTS The study sample comprised 154 patients with a median age of 69. The total numbers of events were 101 for PFS and 60 for OS. The median PFS and OS were 26.1 and 55.4 months, respectively. In the multivariable analysis, EGFR ex 21 L858R mutation (HR: 1.71, 95% CI: 1.15–2.55) and shorter disease-free intervals (HR: 0.98, 95% CI: 0.96–0.99) were significantly associated with shorter PFS. Age (HR: 1.03, 95% CI: 1.00–1.07), smoking history (HR: 2.31, 95% CI: 1.35–3.94) and pathological N2 disease at the initial surgery (HR: 2.30, 95% CI: 1.32–4.00) were significantly associated with shorter OS. CONCLUSIONS First-line EGFR-TKI treatment was generally associated with favourable survival outcomes in patients with postoperative recurrent EGFR-mutated lung adenocarcinoma. EGFR ex 21 L858R mutation may be an important prognostic factor for shorter PFS.

Published
2022

38. Virtual-assisted lung mapping in sublobar resection of small pulmonary nodules, long-term results

Author

Hiroaki Sakai, Jun Nakajima, Yasuhiro Nakashima, Toyofumi F. Chen-Yoshikawa, Keiko Ueda, Terumoto Koike, Masaru Takenaka, Junko Tokuno, Ryuta Fukai, Fumihiro Tanaka, Fumitsugu Kojima, Masashi Kobayashi, Masaaki Sato, Tomoki Nishida, Shinji Kosaka, Jin Sakamoto, Yoshito Yamada, Hiroshi Date, Nobuyuki Yoshiyasu, Kazumichi Yamamoto, Masahiro Yanagiya, Kenji Misawa, Hirokazu Yamaguchi, and Shinji Shinohara

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung Neoplasms, Ground-glass opacity, Bronchoscopy, medicine, Humans, Prospective Studies, Stage (cooking), Pneumonectomy, Lung cancer, Lung, Neoplasm Staging, Retrospective Studies, medicine.diagnostic_test, business.industry, Cancer, General Medicine, medicine.disease, Sublobar resection, medicine.anatomical_structure, Multiple Pulmonary Nodules, Surgery, Radiology, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Wedge resection (lung)
Abstract

OBJECTIVES The short-term efficacy of virtual-assisted lung mapping (VAL-MAP), a preoperative bronchoscopic multi-spot lung-marking technique, has been confirmed in 2 prospective multicentre studies. The objectives of this study were to analyse the local recurrence and survival of patients enrolled in these studies, long-term. METHODS Of the 663 patients enrolled in the 2 studies, 559 patients’ follow-up data were collected. After excluding those who did not undergo VAL-MAP, whose resection was not for curative intent, who underwent concurrent resection without VAL-MAP, or who eventually underwent lobectomy instead of sublobar resection (i.e. wedge resection or segmentectomy), 422 patients were further analysed. RESULTS Among 264 patients with primary lung cancer, the 5-year local recurrence-free rate was 98.4%, and the 5-year overall survival (OS) rate was 94.5%. Limited to stage IA2 or less (≤2 cm in diameter; n = 238, 90.1%), the 5-year local recurrence-free and OS rates were 98.7% and 94.8%, respectively. Among 102 patients with metastatic lung tumours, the 5-year local recurrence-free rate was 93.8% and the 5-year OS rate was 81.8%. Limited to the most common (colorectal) cancer (n = 53), the 5-year local recurrence-free and OS rates were 94.9% and 82.3%, respectively. CONCLUSIONS VAL-MAP, which is beneficial in localizing small barely palpable pulmonary lesions and determining the appropriate resection lines, was associated with reasonable long-term outcomes. Subj collection 152, 1542

Published
2021
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39. Safety and efficacy of depatuxizumab mafodotin in Japanese patients with malignant glioma: A nonrandomized, phase 1/2 trial

Author

Keisuke Ueki, Masayuki Kanamori, Hao Xiong, Yasuko Nishimura, Motoo Nagane, Yoshihiro Muragaki, Masakazu Yamada, Yoshitaka Narita, Kazuhiko Mishima, Masahide Matsuda, Katsunori Asai, Shota Kasai, Toshihiro Kumabe, Naoki Kagawa, Isao Date, Hiroyuki Kobayashi, Jun-ichiro Kuroda, Christopher Ocampo, and Takaaki Beppu

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, temozolomide, Antibodies, Monoclonal, Humanized, Gastroenterology, Drug Therapy, Japan, Clinical Research, Glioma, Internal medicine, medicine, Clinical endpoint, Anti–epidermal growth factor receptor therapy, Humans, depatuxizumab mafodotin, Adverse effect, Aged, Chemotherapy, Temozolomide, business.industry, Brain Neoplasms, Incidence (epidemiology), Gene Amplification, General Medicine, Original Articles, malignant glioma, Chemoradiotherapy, Middle Aged, medicine.disease, Survival Analysis, ErbB Receptors, Treatment Outcome, Oncology, Concomitant, Original Article, Female, Neoplasm Grading, business, medicine.drug, recurrent glioblastoma
Abstract

INTELLANCE‐J was a phase 1/2 study of a potent antibody‐drug conjugate targeting epidermal growth factor receptor (EGFR), depatuxizumab mafodotin (Depatux‐M), as a second‐ or first‐line therapy, alone or combined with chemotherapy or chemoradiotherapy in 53 Japanese patients with World Health Organization (WHO) grade III/IV glioma. In second‐line arms, patients with EGFR‐amplified recurrent WHO grade III/IV glioma received Depatux‐M plus chemotherapy (temozolomide) or Depatux‐M alone regardless of EGFR status. In first‐line arms, patients with newly diagnosed WHO grade III/IV glioma received Depatux‐M plus chemoradiotherapy. The study was halted following lack of survival benefit with first‐line Depatux‐M in the global trial INTELLANCE‐1. The primary endpoint was 6‐month progression‐free survival (PFS) in patients with EGFR‐amplified tumors receiving second‐line Depatux‐M plus chemotherapy. Common nonocular treatment‐emergent adverse events (TEAEs) with both second‐line and first‐line Depatux‐M included lymphopenia (42%, 33%, respectively), thrombocytopenia (39%, 47%), alanine aminotransferase increase (29%, 47%), and aspartate aminotransferase increase (24%, 60%); incidence of grade ≥3 TEAEs was 66% and 53%, respectively. Ocular side effects (OSEs) occurred in 93% of patients receiving second‐line Depatux‐M plus chemotherapy and all patients receiving second‐line Depatux‐M alone or first‐line Depatux‐M plus chemoradiotherapy. Most OSEs were manageable with dose modifications and concomitant medications. The 6‐month PFS estimate was 25.6% (95% confidence interval [CI] 11.4‒42.6), and median PFS was 2.1 months (95% CI 1.9‒3.9) with second‐line Depatux‐M plus chemotherapy in the EGFR‐amplified subgroup. This study showed acceptable safety profile of Depatux‐M alone or plus chemotherapy/chemoradiotherapy in Japanese patients with WHO grade III/IV glioma. The study was registered at ClinicalTrials.gov (NCT02590263)., INTELLANCE‐J was a phase 1/2 study of a potent antibody‐drug conjugate targeting epidermal growth factor receptor (EGFR), depatuxizumab mafodotin, as a second‐ or first‐line therapy, alone or combined with chemotherapy or chemoradiotherapy in Japanese patients with World Health Organization grade III/IV glioma. The results of this trial demonstrate an acceptable safety profile of depatuxizumab mafodotin, with ocular side effects being the most common adverse events that were mostly reversible. Second‐line depatuxizumab mafodotin in combination with temozolomide resulted in a 6‐month progression‐free survival estimate of 25.6% (95% confidence interval 11.4‒42.6) in patients with EGFR‐amplified tumors and showed encouraging antitumor activity in this subgroup of patients (NCT02590263).

Published
2021

40. An End Point-Specific Framework for Read-Across Analog Selection for Human Health Effects

Author

Holger Moustakas, Mihir S. Date, Manoj Kumar, Terry W. Schultz, Daniel C. Liebler, Trevor M. Penning, Daniel T. Salvito, and Anne Marie Api

Subjects
General Medicine, Toxicology
Abstract

Integrating computational chemistry and toxicology can improve the read-across analog approach to fill data gaps in chemical safety assessment. In read-across, structure-related parameters are compared between a target chemical with insufficient test data and one or more materials with sufficient data. Recent advances have focused on enhancing the grouping or clustering of chemicals to facilitate toxicity prediction via read-across. Analog selection ascertains relevant features, such as physical-chemical properties, toxicokinetic-related properties (bioavailability, metabolism, and degradation pathways), and toxicodynamic properties of chemicals with an emphasis on mechanisms or modes of action. However, each human health end point (genotoxicity, skin sensitization, phototoxicity, repeated dose toxicity, reproductive toxicity, and local respiratory toxicity) provides a different critical context for analog selection. Here six end point-specific, rule-based schemes are described. Each scheme creates an end point-specific workflow for filling the target material data gap by read-across. These schemes are intended to create a transparent rationale that supports the selected read-across analog(s) for the specific end point under study. This framework can systematically drive the selection of read-across analogs for each end point, thereby accelerating the safety assessment process.

Published
2022

41. Electromagnetic navigation bronchoscopy-guided radiofrequency identification marking in wedge resection for fluoroscopically invisible small lung lesions

Author

Yojiro Yutaka, Toshihiko Sato, Yu Hidaka, Takao Kato, Hidenao Kayawake, Satona Tanaka, Yoshito Yamada, Akihiro Ohsumi, Daisuke Nakajima, Masatsugu Hamaji, Toshi Menju, and Hiroshi Date

Subjects
Pulmonary and Respiratory Medicine, Surgery, General Medicine, Cardiology and Cardiovascular Medicine
Abstract

OBJECTIVES We developed a novel wireless localization technique after electromagnetic navigation bronchoscopy-guided radiofrequency identification marker placement for fluoroscopically invisible small lung lesions. We conducted an observational study to investigate the feasibility of this technique and retrospectively compared 2 marking approaches with or without cone-beam computed tomography (CBCT). METHODS Consecutive patients from January 2021 to March 2022 in our institution were enrolled. Markers were placed central to the lesions either in a bronchoscopic suite under intravenous anaesthesia or a hybrid operation theatre with CBCT under general anaesthesia. The efficacy of the 2 marking methods was compared using an inverse probability of treatment weighting adjusted analysis. RESULTS Totally 80 markers were placed (45 under CBCT and 35 under fluoroscopy) for 74 patients with 80 lesions [mean size: 6.9 mm (interquartile range: 5.1–8.4) at a median depth from the pleura of 14.0 mm (interquartile range: 8.5–19.5)]. The median distance from marker to lesion was 9.1 mm, with a pleural depth of 15.5 mm. The tumour resection rate was 97.5% (78/80) with the median surgical margin of 10.0 mm (interquartile range: 8.0–11.0). Although the bronchoscopy time was longer using CBCT because of the need for 2.8 scans per lesion, the distance from the marker to the lesion was shorter for marking using CBCT than marking using fluoroscopy (adjusted difference: −4.56, 95% confidence interval: −6.51 to −2.61, P CONCLUSIONS Electromagnetic navigation bronchoscopy-guided radiofrequency identification marking provided a high tumour resection rate with sufficient surgical margins.

Published
2022
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42. Indocyanine green-enhanced thoracoscopic localization of parasternal lymph node: How to do it

Author

Yojiro Yutaka, Masahiro Kawashima, Menju Toshi, Masakazu Toi, and Hiroshi Date

Subjects
Indocyanine Green, Pulmonary and Respiratory Medicine, Treatment Outcome, Sentinel Lymph Node Biopsy, Mediastinum, Humans, Surgery, Lymph Nodes, General Medicine, Cardiology and Cardiovascular Medicine
Abstract

Small, non-palpable, parasternal lymph nodes can be difficult to locate during minimally invasive thoracoscopy. We here present a simple technique for thoracoscopic localization of small parasternal lymph nodes using echo-guided injection of indocyanine green. This technique rapidly marks the whole chain of enhanced lymph nodes for radical resection, enabling accurate endoscopic resection of small parasternal lymph nodes.

Published
2022
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43. Stroke prevention in patients from Latin American countries with non‐valvular atrial fibrillation: Insights from the GARFIELD‐AF registry

Author

Jerjes-Sanchez C., Corbalan R., Barretto A. C. P., Luciardi H. L., Allu J., Illingworth L., Pieper K. S., Kayani G., Fitzmaurice D. A., Goto S., Hacke W., Mantovani L. G., Turpie A. G. G., Gersh B. J., Gibbs H., Brodmann M., Cools F., Connolly S. J., Spyropoulos A., Eikelboom J., Hu D., Jansky P., Nielsen J. D., Ragy H., Raatikainen P., Le Heuzey J. -Y., Darius H., Keltai M., Kakkar S., Sawhney J. P. S., Agnelli G., Ambrosio G., Koretsune Y., Diaz C. J. S., ten Cate H., Atar D., Stepinska J., Panchenko E., Lim T. W., Jacobson B., Oh S., Vinolas X., Rosenqvist M., Steffel J., Angchaisuksiri P., Parkhomenko A., Al Mahmeed W., Chen K. N., Zhao Y. S., Zhang H. Q., Chen J. Z., Cao S. P., Wang D. W., Yang Y. J., Li W. H., Yin Y. H., Tao G. Z., Yang P., Chen Y. M., He S. H., Wang Y., Fu G. S., Li X., Wu T. G., Cheng X. S., Yan X. W., Zhao R. P., Chen M. S., Xiong L. G., Chen P., Jiao Y., Guo Y., Xue L., Wang F. Z., Li H., Yang Z. M., Bai C. L., Chen J., Chen J. Y., Chen X., Feng S., Fu Q. H., Gao X. J., Guo W. N., He R. H., He X. A., Hu X. S., Huang X. F., Li B., Li J., Li L., Li Y. H., Liu T. T., Liu W. L., Liu Y. Y., Lu Z. C., Luo X. L., Ma T. Y., Peng J. Q., Sheng X., Shi X. J., Sun Y. H., Tian G., Wang K., Wang L., Wu R. N., Xie Q., Xu R. Y., Yang J. S., Yang L. L., Yang Q., Ye Y., Yu H. Y., Yu J. H., Yu T., Zhai H., Zhan Q., Zhang G. S., Zhang Q., Zhang R., Zhang Y., Zheng W. Y., Zhou B., Zhou Z. H., Zhu X. Y., Jadhav P., Durgaprasad R., Ravi Shankar A. G., Rajput R. K., Bhargava K., Sarma R., Srinivas A., Roy D., Nagamalesh U. M., Chopda M., Kishore R., Kulkarni G., Chandwani P., Pothiwala R. A., Padinhare Purayil M., Shah S., Chawla K., Kothiwale V. A., Raghuraman B., Vijayaraghavan G., Vijan V. M., Bantwal G., Bisne V., Khan A., Gupta J. B., Kumar S., Jain D., Abraham S., Adak D., Barai A., Begum H., Bhattacharjee P., Dargude M., Davies D., Deshpande B., Dhakrao P., Dhyani V., Duhan S., Earath M., Ganatra A., Giradkar S., Jain V., Karthikeyan R., Kasala L., Kaur S., Krishnappa S., Lawande A., Lokesh B., Madarkar N., Meena R., More P., Naik D., Prashanth K., Rao M., Rao N. M., Sadhu N., Shah D., Sharma M., Shiva P., Singhal S., Suresh S., Vanajakshamma V., Panse S. G., Kanamori S., Yamamoto K., Kumagai K., Katsuda Y., Sadamatsu K., Toyota F., Mizuno Y., Misumi I., Noguchi H., Ando S., Suetsugu T., Minamoto M., Oda H., Shiraishi K., Adachi S., Chiba K., Norita H., Tsuruta M., Koyanagi T., Ando H., Higashi T., Okada K., Azakami S., Komaki S., Kumeda K., Murayama T., Matsumura J., Oba Y., Sonoda R., Goto K., Minoda K., Haraguchi Y., Suefuji H., Miyagi H., Kato H., Nakamura T., Nandate H., Zaitsu R., Fujiura Y., Yoshimura A., Numata H., Ogawa J., Tatematsu H., Kamogawa Y., Murakami K., Wakasa Y., Yamasawa M., Maekawa H., Abe S., Kihara H., Tsunoda S., Saito K., Fudo T., Obunai K., Tachibana H., Oba I., Kuwahata T., Higa S., Gushiken M., Eto T., Yoshida H., Ikeda D., Ishizawa M., Nakatsuka M., Murata K., Ogurusu C., Shimoyama M., Akutsu M., Takamura I., Hoshino F., Yokota N., Iwao T., Tsuchida K., Takeuchi M., Hatori Y., Kitami Y., Nakamura Y., Oyama R., Ageta M., Go Y., Mishima K., Unoki T., Morii S., Shiga Y., Sumi H., Nagatomo T., Sanno K., Fujisawa K., Atsuchi Y., Nagoshi T., Seto T., Tabuchi T., Kameko M., Nii K., Oshiro K., Takezawa H., Nagano S., Miyamoto N., Iwaki M., Fujii M., Okawa M., Abe M., Saito T., Mito T., Nagao K., Minami J., Mita T., Sakuma I., Taguchi T., Marusaki S., Doi H., Tanaka M., Fujito T., Matsuta M., Kusumoto T., Kakinoki S., Ashida K., Yoshizawa N., Agata J., Arasaki O., Manita M., Ikemura M., Fukuoka S., Murakami H., Matsukawa S., Hata Y., Taniguchi T., Ko T., Kubo H., Imamaki M., Akiyama M., Inagaki M., Odakura H., Ueda T., Katsube Y., Nakata A., Watanabe H., Techigawara M., Igarashi M., Taga K., Kimura T., Tomimoto S., Shibuya M., Nakano M., Ito K., Seo T., Hiramitsu S., Hosokawa H., Hoshiai M., Hibino M., Miyagawa K., Horie H., Sugishita N., Soma A., Neya K., Yoshida T., Mizuguchi M., Ishiguro M., Minagawa T., Wada M., Mukawa H., Okuda F., Nagasaka S., Abe Y., Adachi T., Akahane K., Amano T., Aoki K., Aoyama T., Arai H., Arima S., Arino T., Asano H., Asano T., Azuma J., Baba T., Betsuyaku T., Chibana H., Date H., Doiuchi J., Emura Y., Endo M., Fujii Y., Fujiki R., Fujisawa A., Fujisawa Y., Fukuda T., Fukui T., Furukawa N., Furukawa T., Furumoto W., Goto T., Hamaoka M., Hanazono N., Hasegawa K., Hatsuno T., Hayashi Y., Higuchi K., Hirasawa K., Hirayama H., Hirose M., Hirota S., Honda M., Ido T., Iiji O., Ikeda H., Ikeda K., Ikeoka K., Imaizumi M., Inaba H., Inoue T., Iseki F., Ishihara A., Ishioka N., Ito N., Iwase T., Kakuda H., Kamata J., Kanai H., Kanda H., Kaneko M., Kano H., Kasai T., Kato T., Kato Y., Kawada Y., Kawai K., Kawakami K., Kawakami S., Kawamoto T., Kawano S., Kim J., Kira T., Kitazawa H., Kitazumi H., Kito T., Kobayashi T., Koeda T., Kojima J., Komatsu H., Komatsu I., Koshibu Y., Kotani T., Kozuka T., Kumai Y., Kumazaki T., Maeda I., Maeda K., Maruyama Y., Matsui S., Matsushita K., Matsuura Y., Mineoi K., Mitsuhashi H., Miura N., Miyaguchi S., Miyajima S., Miyamoto H., Miyashita A., Miyata S., Mizuguchi I., Mizuno A., Mori T., Moriai O., Morishita K., Murai O., Nagai S., Nagata E., Nagata H., Nakagomi A., Nakahara S., Nakamura M., Nakamura R., Nakanishi N., Nakayama T., Nakazato R., Nanke T., Nariyama J., Niijima Y., Niinuma H., Nishida Y., Nishihata Y., Nishino K., Nishioka H., Nishizawa K., Niwa I., Nomura K., Nomura S., Nozoe M., Ogawa T., Ohara N., Okada M., Okamoto K., Okita H., Okuyama M., Ono H., Ono T., Pearce Y. O., Oriso S., Ota A., Otaki E., Saito Y., Sakai H., Sakamoto N., Sakamoto Y., Samejima Y., Sasagawa Y., Sasaguri H., Sasaki A., Sasaki T., Sato K., Sawano M., Seki S., Sekine Y., Seta Y., Sezaki K., Shibata N., Shiina Y., Shimono H., Shimoyama Y., Shindo T., Shinohara H., Shinohe R., Shinozuka T., Shirai T., Shiraiwa T., Shozawa Y., Suga T., Sugimoto C., Suzuki K., Suzuki S., Suzuki Y., Tada M., Taguchi A., Takagi T., Takagi Y., Takahashi K., Takahashi S., Takai H., Takanaka C., Take S., Takeda H., Takei K., Takenaka K., Tana T., Tanabe G., Taya K., Teragawa H., Tohyo S., Toru S., Tsuchiya Y., Tsuji T., Tsuzaki K., Uchiyama H., Ueda O., Ueyama Y., Wakaki N., Wakiyama T., Washizuka T., Watanabe M., Yamada T., Yamagishi T., Yamaguchi H., Yamamoto T., Yamaura M., Yamazoe M., Yasui K., Yokoyama Y., Yoshida K., Ching C. K., Foo C. G., Chow J. H., Chen D. D., Jaufeerally F. R., Lee Y. M., Lim G., Lim W. T., Thng S., Yap S. Y., Yeo C., Pak H. N., Kim J. -B., Kim J. H., Jang S. -W., Kim D. H., Ryu D. R., Park S. W., Kim D. -K., Choi D. J., Oh Y. S., Cho M. -C., Kim S. -H., Jeon H. -K., Shin D. -G., Park J. S., Park H. K., Han S. -J., Sung J. H., Cho J. -G., Nam G. -B., On Y. K., Lim H. E., Kwak J. J., Cha T. -J., Hong T. J., Park S. H., Yoon J. H., Kim N. -H., Kim K. -S., Jung B. C., Hwang G. -S., Kim C. -J., Kim D. B., Ahn J. J., An H. J., Bae H., Baek A. L., Chi W. J., Choi E. A., Choi E. H., Choi H. K., Choi H. S., Han S., Heo E. S., Her K. O., Hwang S. W., Jang E. M., Jang H. -S., Jang S., Jeon H. -G., Jeon S. R., Jeon Y. R., Jeong H. K., Jung I. -A., Kim H. J., Kim J. S., Kim J. A., Kim K. T., Kim M. S., Kim S. H., Kim Y. -I., Lee C. S., Lee E. H., Lee G. H., Lee H. Y., Lee H. -Y., Lee K. H., Lee K. R., Lee M. S., Lee M. -Y., Lee R. W., Lee S. E., Lee S. H., Lee S., Lee W. Y., Noh I. K., Park A. R., Park B. R., Park H. N., Park J. H., Park M., Park Y., Seo S. -Y., Shim J., Sim J. H., Sohn Y. M., Son W. S., Son Y. S., Song H. J., Wi H. K., Woo J. J., Ye S., Yim K. H., Yoo K. M., Yoon E. J., Yun S. Y., Chawanadelert S., Mongkolwongroj P., Kanokphatcharakun K., Cheewatanakornkul S., Laksomya T., Pattanaprichakul S., Chantrarat T., Rungaramsin S., Silaruks S., Wongcharoen W., Siriwattana K., Likittanasombat K., Katekangplu P., Boonyapisit W., Cholsaringkarl D., Chatlaong B., Chattranukulchai P., Santanakorn Y., Hutayanon P., Khunrong P., Bunyapipat T., Jai-Aue S., Kaewsuwanna P., Bamungpong P., Gunaparn S., Hongsuppinyo S., Inphontan R., Khattaroek R., Khunkong K., Kitmapawanont U., Kongsin C., Naratreekoon B., Ninwaranon S., Phangyota J., Phrommintikul A., Phunpinyosak P., Pongmorakot K., Poomiphol S., Pornnimitthum N., Pumprueg S., Ratchasikaew S., Sanit K., Sawanyawisuth K., Silaruks B., Sirichai R., Sriwichian A., Suebjaksing W., Sukklad P., Suttana T., Tangsirira A., Thangpet O., Tiyanon W., Vorasettakarnkij Y., Wisaratapong T., Wongtheptien W., Wutthimanop A., Yawila S., Altun A., Ozdogru I., Ozdemir K., Yilmaz O., Aydinlar A., Yilmaz M. B., Yeter E., Ongen Z., Cayli M., Pekdemir H., Ozdemir M., Sucu M., Sayin T., Demir M., Yorgun H., Ersanli M., Okuyan E., Aras D., Abdelrahman H., Aktas O., Alpay D., Aras F., Bireciklioglu M. F., Budeyri S., Buyukpapuc M., Caliskan S., Esen M., Felekoglu M. A., Genc D., Ikitimur B., Karaayvaz E. B., Karatas S. K., Okutucu S., Ozcelik E., Quisi A., Sag H., Sahiner L., Sayin B. Y., Seker T., Alkan D. U., Yildirim E., Yildirim R., Yilmaz F., Yuksekdag V., Vensentini N., Ingaramo A. C., Sambadaro G. A., Caputi V. F., Berman S. G., Dragotto P., Kleiban A. J., Centurion N., Giacomi G., Guerrero R. A. A., Conde D., Zapata G., Di Paola L. A., Ramos J. L., Dran R. D., Egido J., Fernandez A. A., Fosco M. J., Sassone S., Sinisi V. A., Cartasegna L. R., Berli M. A., Vilamajo O. A. G., Ferroni F., Alaguibe E. D., D'Amelio A. A., Arabetti C., Arias L., Belardi J. A., Bergesio L., Berli F., Berli M., Borchowiec S., Buzzetti C., Cabrini R., Campisi V., Cappi A. L., Carrizo R., Berra F. C., Costabel J. P., Costamagna O. J. A., Damonte A. A., De Urquiza I. N., Diez F., Eden M. F., Fanuele M., Voena F. F., Torres M. F., Funosas C., Giacomi M. P., Gimenez C. H., Gurfinkel E. P., Had M. D. L. M., Hansen V., Hrabar A. D., Ingratta M., Lopez A., Maehara G., Maffei L., Martinelli A., Martinelli C., Matkovich J., Mautner B., Meirino A., Munguia R., Navarro A., Novas V., Prados G. P., Pontoriero J., Potito R. N., Ricotti C., Rodriguez M. A., Rolandi F., Palladino M. E. S., Salinger M., Sanziani L. S., Schygiel P. O., Sossich A., Tinto J. F., Tonelli L., Tufare A. L., Vallejo M., Yunis M. E., Zillo M., Zurbrigk F. J., Filho D. C. S., Jaber J., Armaganijan D., Neto J. F., Steffens A., de Souza W. K. S. B., de Souza Neto J. D., Ribeiro J. M., Teixeira M. S., Rossi P. R. F., Pires L., Moreira D., Jorge J. C. M., Filho A. M. L., Bodanese L. C., Montera M. W., Del Carlo C. H., Rodrigues T. D. R., da Costa F. A. A., Lopes A., Lopes R., Araujo G. R., Manenti E. R. F., Saraiva J. F. K., Braga J. C. F., Negri A., Souto L., Moncada C., Precoma D. B., Roquette F., Reis G., Filho R. A. R., Figueiredo E. L., Botelho R. V., Tavares C. M. D. F., Frack C. R. C., Saad J. A., Finimundi H. C., Pisani C., Chemello D., Martins M. P., Franca C. C. B., Alban F., Rosito G. B. A., Moraes Junior J. B. M. X., Tumelero R. T., Maia L. N., de Almeida R. S., do Carmo Borges N. C., Ferreira L. G. G., Agliardi P., Gomes J. A. O., Araujo V., Nakazone M. A., Barbosa T., Barroso S., Falchetto E. B., Lopes H. B., Lemos M. A. B. T., Biazus G., Queiroz L. B., Camazzola F. E., Caporale M., Cardoso Boscato S., Chieza F., Chokr M. O., Mingireanov R. C., Goes N. C., Correa C., Costa M., Ortiz C. C., da Silva L. S., Paulitsch F. D. S., da Silveira J. A., Daros E., de Araujo G. R., Del Monaco M. I., Dias C., Dias M. A., Wainstein A. P. D., Pizzato P. E., Esteves D. C., Fabri P., Fonseca T. F. L., Fernandes E., Fonseca C., Costantini C. R. F., Ferraz R. F., Freire F., Gottardo P., Guanaes D., Guizzardi S., Magedanz E. H., Igansi F., Jannuzzi F., Junior G., Komar D., Lino E. G., Lopes D., Junior O. L. D. S., Lustosa E., Macagnan A. P., Marinho M. C., Mazzoni M., Melo G., Mortari L., Mouco O. M. C. C., Vital C. N., Ormundo C., Emmer S. O., Palmegiani E., Pavani R., Pereira L., Pereira V. L., Perreira R., Poletti S., Fortunato S. C. Q., Queirantes C., Pereira N. R., Rech R. L., Ribeiro S., Rodrigues A., Roesch H., Reichert T. R., Santos D., Santos I., Santos M., Seroqui M. V., Silva S., Soares L., Spolaor L., Stoll C., Duda N. T., Trama L., Unterkircher B., Valois M. V., Vargas T., Viana T., Vicente C., Armaganijan L. V., Homem R. V., Torres L. G. V., Vila L., Filho F. V. G., Eggers G., Gutierrez C. B., Arriagada G., Cardenas S. P., Fernandez B. A. J. S., Conejeros C., Houzvic C., Cuevas P. M., Montecinos H., Forero A., Lanas F., Gomez M. L., Vilches G. C., Rey C., Astudillo C., Aguilar J., Campisto Y., Lara C., Molina E., Oyarzon J. M., Olguin V., Vergara M., Villan C., Diaz J. I., Cantu R. L., Zavala M. G. R., Jardines R. C., Zavaleta N. E., Umana S. V., Rosas E. L., Esperon G. L., Pozas G., Munoz E. C., Hernandez N. M., Rendon A. L., Hernandez N. G., Ibarra M. L. R., Carrillo L. V., Villezca D. L., Herrera C. H., Prieto J. J. L., Rodriguez R. G., Espinosa E. V., Martinez D. F., Barcena J. V., Yong R., Briones I. R., Pons J. L. L., Lopez H. A., Ruiz R. O., de la Vega C. D., Brito C. C., Valenzuela E. C., Reyes-Sanchez R., Ruiz A. B., Flores O. N., Gonzalez M. B., Nava R. A., Cerda J. D. M., Fierro O. F., Campos P. F., Alfaro T. A. A., Bellorin S. A., Avena R., Chavarria M., Espinosa I., Silva F. F., Nava R. H. G., Godoy K., Felix E. J. G., Garcia C. L. G., Salas L. G. G., Guajardo P., Gonzalez S. H., Izquierdo T., Ortiz M. C. M., Vasquez D. M., Mendoza N., Morales J., Nikitina N., Aybar S. O., Ortiz A., Macias P. P., Perez F., Sanchez J. A. P., Toledano S. P., Gonzalez M. R., Ramos C. R., Castro V. R., Cardona G. R., Cornejo M. R., Salinas A., Santana G., Perez P. S., Castaneda A. C. T., Cortes R. T., Lenz K., Drexel H., Foechterle J., Hagn C., Podczeck-Schweighofer A., Huber K., Winkler M., Schneeweiss B., Gegenhuber A., Lang W., Eichinger-Hasenauer S., Kaserer P., Sykora J., Rasch H., Pichler M., Schaflinger E., Strohmer B., Breier R., Ebner K. -M., Eischer L., Freihoff F., Lischka-Lindner A., Mark T., Mirtl A., Said A., Stocklocker C., Vogel B., Vonbank A., Wohrer C., Zanolin D., Paparella G., Vandergoten P., Parque J. -L., Capiau L., Vervoort G., Wollaert B., Desfontaines P., Mairesse G., Boussy T., Godart P., De Wolf A., Voet J., Heyse A., Hollanders G., Anne W., Vercammen J., Purnode P., Blankoff I., Faes D., Balthazar Y., Beutels M., Marechal P., Verstraete S., Xhaet O., Striekwold H., Thoeng J., Hermans K., Alzand B., Ascoop A. -K., Banaeian F., Barbuto A. -M., Billiaux A. C., Blockmans M., Bouvy C., Brike C., Capiau H., Casier T., Bolado A. C. Y., De Cleen D., De Coninck M., de Vos M., de Weerdt N., Delforge M., Delvigne M., Denie D., Derycker K., Deweerd E., Dormal F., Drieghe S., Everaert M., Eykerman T., Feys E., Ghekiere M., Gits F., Hellemans S., Helvasto L., Jacobs C., Lips S., Mestdagh I., Nimmegeers J., Piamonte V., Pollet P., Postolache A., Raepers M., Raymenants E., Richa J., Rombouts H., Salembier J., Scheurwegs C., Semeraro O., Simons N., Smessaert C., Smolders W., Stockman I., Tahon S., Thyssen V., Tincani G., Van Durme F., Van Lier D., Vandekerckhove H., Vandekerckhove Y., Vandenbroeck D., Vandorpe A., Vanhalst E., Vanhauwaert B., Vantomme C., Vergauwen L., Verloove H., Vydt T., Weyn T., Reichert P., Spacek R., Machova V., Zidkova E., Ludka O., Olsr J., Kotik L., Plocova K., Racz B., Ferkl R., Hubac J., Kotik I., Monhart Z., Burianova H., Jerabek O., Pisova J., Petrova I., Dedek V., Honkova M., Podrazil P., Spinar J., Vitovec J., Novak M., Lastuvka J., Durdil V., Antonova P., Bockova L., Bultas J., Chlumsky J., Dastychova L., Drasnar T., Honek J., Horejsi M., Hubacova V., Janska L., Kopeckova I., Kratochvilova R., Krcova E., Labrova R., Lindourkova A., Lipoldova J., Lubanda H., Ludkova A., Mahdalikova L., Majernikova M., Michalik D., Potuznik P., Prochazkova E., Sulc A., Sveceny J., Valtova M., Zidek M., Zika J., Nielsen H., Husted S., Hintze U., Rasmussen S., Bremmelgaard A., Markenvard J., Boerger J., Solgaard J., Simonsen P., Loekkegaard T., Bruun M., Mertz J., Dominguez H., Skagen K., Egstrup K., Ibsen H., Raymond I., Bang-Hansen T., Ellervik C., Eriksen E., Jensen L., Jensen M., Leth M., Nygaard A., Park J., Schou M., Therkelsen A., Tilma J., Vesterager K., Airaksinen J., Arola O., Koistinen J., Nappila H., Peltomaki K., Rasanen V., Vasankari T., Galinier M., Gottwalles Y., Paganelli F., Loiselet P., Muller J. -J., Koujan M. B., Marquand A., Destrac S., Piot O., Delarche N., Cebron J. -P., Boveda S., Guenoun M., Guedj-Meynier D., Galley D., Ohayon J., Assouline S., Zuber M., Amarenco P., Ellie E., Kadouch J., Fournier P. -Y., Huberman J. -P., Lemaire M., Rodier G., Milandre L., Vandamme X., Sibon I., Neau J. -P., Mahagne M. H., Mielot A., Bonnefoy M., Churet J. -B., Navarre V., Sellem F., Monniot G., Boyes J. -P., Doucet B., Martelet M., Obadia D., Crousillat B., Mouallem J., Bearez E., Nazeyrollas P., Brugnaux J. 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C., Sabir A., Choudhary F., Khalaque S., Wilson A., Peters S., Coulson W., Roberts N., Heer A., Coates S., Ward B., Jackson D., Walton S., Shepherd D., Sterry M., Wong T., Boon M., Bunney R., Haria-Shah R., Baron R. T., Davies S., Schatzberger T., Hargreaves N., Stephenson T., Choi H., Batson R., Lucraft L., Myhill T., Estifano S., Geatch D., Wilkinson J., Veale R., Forshaw K., Davies T., Zaman K., Vinson P., Liley C., Bandrapalli M., McGinty P., Wastling R., McEleny P., Beattie A., Cooke P., Wong M., Gunasegaram J., Pugsley M., Ahmad S., A'Court C., Ayers J., Bennett J., Cartwright S., Dobson S., Dooldeniya C., Flynn A., Fox R., Goram J., Halpin A., Hay A., Jacobs P., Jeffers L., Lomax L., Munro I., Muvva R., Nadaph M., Powell K., Randfield S., Redpath D., Reed R., Rickenbach M., Rogers G., Saunders P. 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M., Singh R., Naguib A., Abu-Mahfouz M., Al Omairi M., Al Naeemi A., Maruthanayagam R., Bazargani N., Wassef A., Gupta R., Khan M., Subbaraman B., Abdul A., Al Mulla A., El Bardisy S., Haridas P., Jadhav S., Magdaluyo K., Makdad M., Maqsood I., Mohamed R., Sharma N., Sharma R., Thanzeel M., Canosa R., Rama P., Blumberg E., Garcia J., Mullen P., Wilson V., Quick A., Ferrick K., Kutayli W. M., Cox M., Franco M., Falkowski S., Mendelson R., Williams M., Miller S., Beach S., Alfieri A., Gutowski T., Haque I., Reddy R., Ahmed W., Delafontaine P., Diercks D., Theodoro D., Remmel K., Alberts M., Ison R., Noveck H., Duffy P., Pitta S., Nishijima D., Treasure C., Asafu-Adjaye N., Ball K., Bartlett M., Bentley M., Bowers S., Brown A., Browne A., Cameron-Watts J., Canova M., Cassidy D., Cervellione K., Congal S., DePauw J., Dickerson A., Eley M., Evans L., Felpel S., Ferdinand K., Fielder D., Gentry P., Haideri A., Hakimi F., Harbour T., Hartranft E., Hawkins B., Headlee M., Henson L., Herrick C., Hicks T., Jasinski S., Jones A., Jones L., Jones P., Karl S., Keeling M., Kerr J., Knowles P., Langdon J., Lay M., Lee J. A., Lincoln T., Malone E., Merliss A., Merritt D., Minardo J., Mooso B., Orosco C., Palumbo V., Parker M., Parrott T., Paserchia S., Pearl G., Peterson J., Pickelsimer N., Purcell T., Raynor J., Raziano S., Richard C., Richardson T., Robertson C., Sage A., Sanghera T., Shaw P., Shoemaker J., Smith K., Stephanie B., Thatcher A., Theobald H., Thompson N., Treasure L., Tripti T., Verdi C., Worthy V., Jerjes-Sanchez, C, Corbalan, R, Barretto, A, Luciardi, H, Allu, J, Illingworth, L, Pieper, K, Kayani, G, Fitzmaurice, D, Goto, S, Hacke, W, Mantovani, L, Turpie, A, Gersh, B, Gibbs, H, Brodmann, M, Cools, F, Connolly, S, Spyropoulos, A, Eikelboom, J, Hu, D, Jansky, P, Nielsen, J, Ragy, H, Raatikainen, P, Le Heuzey, J, Darius, H, Keltai, M, Kakkar, S, Sawhney, J, Agnelli, G, Ambrosio, G, Koretsune, Y, Diaz, C, ten Cate, H, Atar, D, Stepinska, J, Panchenko, E, Lim, T, Jacobson, B, Oh, S, Vinolas, X, Rosenqvist, M, Steffel, J, Angchaisuksiri, P, Parkhomenko, A, Al Mahmeed, W, Chen, K, Zhao, Y, Zhang, H, Chen, J, Cao, S, Wang, D, Yang, Y, Li, W, Yin, Y, Tao, G, Yang, P, Chen, Y, He, S, Wang, Y, Fu, G, Li, X, Wu, T, Cheng, X, Yan, X, Zhao, R, Chen, M, Xiong, L, Chen, P, Jiao, Y, Guo, Y, Xue, L, Wang, F, Li, H, Yang, Z, Bai, C, Chen, X, Feng, S, Fu, Q, Gao, X, Guo, W, He, R, He, X, Hu, X, Huang, X, Li, B, Li, J, Li, L, Li, Y, Liu, T, Liu, W, Liu, Y, Lu, Z, Luo, X, Ma, T, Peng, J, Sheng, X, Shi, X, Sun, Y, Tian, G, Wang, K, Wang, L, Wu, R, Xie, Q, Xu, R, Yang, J, Yang, L, Yang, Q, Ye, Y, Yu, H, Yu, J, Yu, T, Zhai, H, Zhan, Q, Zhang, G, Zhang, Q, Zhang, R, Zhang, Y, Zheng, W, Zhou, B, Zhou, Z, Zhu, X, Jadhav, P, Durgaprasad, R, Ravi Shankar, A, Rajput, R, Bhargava, K, Sarma, R, Srinivas, A, Roy, D, Nagamalesh, U, Chopda, M, Kishore, R, Kulkarni, G, Chandwani, P, Pothiwala, R, Padinhare Purayil, M, Shah, S, Chawla, K, Kothiwale, V, Raghuraman, B, Vijayaraghavan, G, Vijan, V, Bantwal, G, Bisne, V, Khan, A, Gupta, J, Kumar, S, Jain, D, Abraham, S, Adak, D, Barai, A, Begum, H, Bhattacharjee, P, Dargude, M, Davies, D, Deshpande, B, Dhakrao, P, Dhyani, V, Duhan, S, Earath, M, Ganatra, A, Giradkar, S, Jain, V, Karthikeyan, R, Kasala, L, Kaur, S, Krishnappa, S, Lawande, A, Lokesh, B, Madarkar, N, Meena, R, More, P, Naik, D, Prashanth, K, Rao, M, Rao, N, Sadhu, N, Shah, D, Sharma, M, Shiva, P, Singhal, S, Suresh, S, Vanajakshamma, V, Panse, S, Kanamori, S, Yamamoto, K, Kumagai, K, Katsuda, Y, Sadamatsu, K, Toyota, F, Mizuno, Y, Misumi, I, Noguchi, H, Ando, S, Suetsugu, T, Minamoto, M, Oda, H, Shiraishi, K, Adachi, S, Chiba, K, Norita, H, Tsuruta, M, Koyanagi, T, Ando, H, Higashi, T, Okada, K, Azakami, S, Komaki, S, Kumeda, K, Murayama, T, Matsumura, J, Oba, Y, Sonoda, R, Goto, K, Minoda, K, Haraguchi, Y, Suefuji, H, Miyagi, H, Kato, H, Nakamura, T, Nandate, H, Zaitsu, R, Fujiura, Y, Yoshimura, A, Numata, H, Ogawa, J, Tatematsu, H, Kamogawa, Y, Murakami, K, Wakasa, Y, Yamasawa, M, Maekawa, H, Abe, S, Kihara, H, Tsunoda, S, Saito, K, Fudo, T, Obunai, K, Tachibana, H, Oba, I, Kuwahata, T, Higa, S, Gushiken, M, Eto, T, Yoshida, H, Ikeda, D, Ishizawa, M, Nakatsuka, M, Murata, K, Ogurusu, C, Shimoyama, M, Akutsu, M, Takamura, I, Hoshino, F, Yokota, N, Iwao, T, Tsuchida, K, Takeuchi, M, Hatori, Y, Kitami, Y, Nakamura, Y, Oyama, R, Ageta, M, Go, Y, Mishima, K, Unoki, T, Morii, S, Shiga, Y, Sumi, H, Nagatomo, T, Sanno, K, Fujisawa, K, Atsuchi, Y, Nagoshi, T, Seto, T, Tabuchi, T, Kameko, M, Nii, K, Oshiro, K, Takezawa, H, Nagano, S, Miyamoto, N, Iwaki, M, Fujii, M, Okawa, M, Abe, M, Saito, T, Mito, T, Nagao, K, Minami, J, Mita, T, Sakuma, I, Taguchi, T, Marusaki, S, Doi, H, Tanaka, M, Fujito, T, Matsuta, M, Kusumoto, T, Kakinoki, S, Ashida, K, Yoshizawa, N, Agata, J, Arasaki, O, Manita, M, Ikemura, M, Fukuoka, S, Murakami, H, Matsukawa, S, Hata, Y, Taniguchi, T, Ko, T, Kubo, H, Imamaki, M, Akiyama, M, Inagaki, M, Odakura, H, Ueda, T, Katsube, Y, Nakata, A, Watanabe, H, Techigawara, M, Igarashi, M, Taga, K, Kimura, T, Tomimoto, S, Shibuya, M, Nakano, M, Ito, K, Seo, T, Hiramitsu, S, Hosokawa, H, Hoshiai, M, Hibino, M, Miyagawa, K, Horie, H, Sugishita, N, Soma, A, Neya, K, Yoshida, T, Mizuguchi, M, Ishiguro, M, Minagawa, T, Wada, M, Mukawa, H, Okuda, F, Nagasaka, S, Abe, Y, Adachi, T, Akahane, K, Amano, T, Aoki, K, Aoyama, T, Arai, H, Arima, S, Arino, T, Asano, H, Asano, T, Azuma, J, Baba, T, Betsuyaku, T, Chibana, H, Date, H, Doiuchi, J, Emura, Y, Endo, M, Fujii, Y, Fujiki, R, Fujisawa, A, Fujisawa, Y, Fukuda, T, Fukui, T, Furukawa, N, Furukawa, T, Furumoto, W, Goto, T, Hamaoka, M, Hanazono, N, Hasegawa, K, Hatsuno, T, Hayashi, Y, Higuchi, K, Hirasawa, K, Hirayama, H, Hirose, M, Hirota, S, Honda, M, Ido, T, Iiji, O, Ikeda, H, Ikeda, K, Ikeoka, K, Imaizumi, M, Inaba, H, Inoue, T, Iseki, F, Ishihara, A, Ishioka, N, Ito, N, Iwase, T, Kakuda, H, Kamata, J, Kanai, H, Kanda, H, Kaneko, M, Kano, H, Kasai, T, Kato, T, Kato, Y, Kawada, Y, Kawai, K, Kawakami, K, Kawakami, S, Kawamoto, T, Kawano, S, Kim, J, Kira, T, Kitazawa, H, Kitazumi, H, Kito, T, Kobayashi, T, Koeda, T, Kojima, J, Komatsu, H, Komatsu, I, Koshibu, Y, Kotani, T, Kozuka, T, Kumai, Y, Kumazaki, T, Maeda, I, Maeda, K, Maruyama, Y, Matsui, S, Matsushita, K, Matsuura, Y, Mineoi, K, Mitsuhashi, H, Miura, N, Miyaguchi, S, Miyajima, S, Miyamoto, H, Miyashita, A, Miyata, S, Mizuguchi, I, Mizuno, A, Mori, T, Moriai, O, Morishita, K, Murai, O, Nagai, S, Nagata, E, Nagata, H, Nakagomi, A, Nakahara, S, Nakamura, M, Nakamura, R, Nakanishi, N, Nakayama, T, Nakazato, R, Nanke, T, Nariyama, J, Niijima, Y, Niinuma, H, Nishida, Y, Nishihata, Y, Nishino, K, Nishioka, H, Nishizawa, K, Niwa, I, Nomura, K, Nomura, S, Nozoe, M, Ogawa, T, Ohara, N, Okada, M, Okamoto, K, Okita, H, Okuyama, M, Ono, H, Ono, T, Pearce, Y, Oriso, S, Ota, A, Otaki, E, Saito, Y, Sakai, H, Sakamoto, N, Sakamoto, Y, Samejima, Y, Sasagawa, Y, Sasaguri, H, Sasaki, A, Sasaki, T, Sato, K, Sawano, M, Seki, S, Sekine, Y, Seta, Y, Sezaki, K, Shibata, N, Shiina, Y, Shimono, H, Shimoyama, Y, Shindo, T, Shinohara, 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Subjects
Registrie, Male, Latin Americans, 030204 cardiovascular system & hematology, outcomes, 0302 clinical medicine, Drug Prescription, Retrospective Studie, Risk Factors, Atrial Fibrillation, Antithrombotic, Prospective Studies, Registries, 030212 general & internal medicine, Practice Patterns, Physicians', Stroke, Anticoagulant, Atrial fibrillation, General Medicine, Middle Aged, Treatment Outcome, Stroke prevention, outcome, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, Human, medicine.medical_specialty, medicine.drug_class, Clinical Investigations, Hemorrhage, antithrombotic treatment, Drug Prescriptions, 03 medical and health sciences, Internal medicine, medicine, Humans, Mexico, Aged, Retrospective Studies, Fibrillation, business.industry, Risk Factor, Anticoagulants, South America, medicine.disease, Drug Utilization, Clinical trial, Prospective Studie, Latin American, antithrombotic treatment, atrial fibrillation, Latin American, outcomes, business
Abstract

Author(s): Jerjes-Sanchez, Carlos; Corbalan, Ramon; Barretto, Antonio CP; Luciardi, Hector L; Allu, Jagan; Illingworth, Laura; Pieper, Karen S; Kayani, Gloria; GARFIELD-AF Investigators | Abstract: BackgroundAtrial fibrillation (AF) is an important preventable cause of stroke. Anticoagulation (AC) therapy can reduce this risk. However, prescribing patterns and outcomes in patients with non-valvular AF (NVAF) from Latin American countries are poorly described.MethodsUsing data from the Global Anticoagulant Registry in the FIELD-AF (GARFIELD-AF), we examined the stroke prevention strategies and the 1-year outcomes in patients from four Latin American countries: Argentina, Brazil, Chile, and Mexico.ResultsA total of 4162 patients (2010-2014) were included in this analysis. At the time of AF diagnosis, 39.9% of patients were prescribed vitamin K antagonists (VKA) ± antiplatelet (AP) therapy, 21.8% non-VKA oral anticoagulant (NOAC) ± AP, 24.1% AP only and 14.1% no antithrombotic treatment. The proportion of moderate-high risk patients receiving no AC therapy at participating centers was highest in Mexico (46.4%) and lowest in Chile (14.3%). During 1-year follow-up, the rates of all-cause mortality, stroke/SE and major bleeding were: 5.77 (95% CI) (5.06-6.56), 1.58 (1.23-2.02), and 0.99 (0.72-1.36) and per 100 person-years, respectively, which are higher than the global rates across all countries in GARFIELD-AF. Unadjusted rates of all-cause mortality were highest in Argentina, 6.95 (5.43-8.90), and lowest in Chile, 4.01 (2.92-5.52).ConclusionsGARFIELD-AF results describes the marked variation in the baseline characteristics and patterns of antithrombotic treatments in patients with NVAF in four Latin American countries. Over one-third of patients with a moderate-to-high risk of stroke received no AC therapy, highlighting the need for improved management of patients according to national guideline. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.

Published
2019
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44. A primary thymic adenocarcinoma with two components that traced distinct evolutionary trajectories

Author

Yoshihiro Ishida, Hironori Haga, Yosuke Yamada, Ayami Ishida, Akihiko Yoshizawa, Alexander Marx, Daisuke Nakajima, and Hiroshi Date

Subjects
thymic adenocarcinoma, Mutation, Pathology, medicine.medical_specialty, whole-genome doubling, Microsatellite instability, General Medicine, Biology, medicine.disease, medicine.disease_cause, Pathology and Forensic Medicine, Lesion, CDKN2A, medicine, thymic cysts, Adenocarcinoma, Microsatellite, microsatellite instability, KRAS, medicine.symptom, Thymic Adenocarcinoma
Abstract

Even though it is a rare subtype, identifying the genetic features of thymic adenocarcinoma is valuable for a multifaceted understanding of thymic epithelial tumors. We experienced a female patient with thymic adenocarcinoma associated with thymic cysts. The tumor consisted of a solid whitish lesion (lesion-1) and a large cystic lesion with small papillary nodules (lesion-2). Microscopically, lesion-1 exhibited poorly differentiated adenocarcinoma accompanying numerous inflammatory cell infiltrates, and lesion-2 (the nodules within the cystic lesion) exhibited enteric-type adenocarcinoma. Consistent with the histological difference, whole-exome sequencing revealed that these two components exhibited distinct genetic features, except for only a few shared mutations, including CDKN2A truncation. Lesion-1 exhibited microsatellite instability-high signature with high mutation burden, for which immune checkpoint inhibitors might apply; and lesion-2 exhibited whole-genome doubling with KRAS hotspot mutation. Our case presents novel genetic features of thymic adenocarcinoma and demonstrates that distinct mutational processes can be operative within a single tumor.

Published
2021
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45. Effect of Organic Fertilizer on Tomato Growth and Production under Soil-less System

Author

Mateus De Freitas Ramos, Osvaldo Kiyoshi Yamanishi, Shuichi Date, Andre Freire Cruz, and Kiyotaka Murakami

Subjects
chemistry.chemical_compound, chemistry, Agronomy, Phosphorus, Chlorophyll, fungi, Fulvic acid, food and beverages, chemistry.chemical_element, Production (economics), General Medicine, Organic fertilizer
Abstract

Soil-less system constitutes an efficient approach for the cultivation of tomato; however, organic liquid amendments are very limited under such systems. The current experiment aimed to evaluate the effects of Kurojiru (K), an organic liquid fertilizer and fulvic acid (FA) on the growth and production of tomato, Solanum lycopersicum L. cv. ‘Momotaro’. Recently, it is desirable to reduce the environmental impact and fertilizer cost by lowering the concentration of inorganic components in the culture medium. Therefore, we explored the effect of adding these organic fertilizers on the yield and quality of tomatoes by gradually reducing the phosphoric acid concentration in the culture medium (87, 58 and 29 mmol・pot-1・week-1). The whole experiment was conducted for 20 weeks (from seeding until harvesting). The plant biomass, tomato fruit weight and chlorophyll content were measured. The fresh weight (FW) of both root and shoot indicated a progress response according to phosphorus concentration in liquid media, in FA treatments. Total fresh weight was significantly higher in the treatment with K+FA than in the control. Additionally, the yield responded to the all treatments within the 58 mmol P. Especially, in this level of P the relative fruit weight was higher only under K application. The chlorophyll content responded K+FA treatment under a low P content (29 mmol), and to all of those in 58 mmol. These results indicate that Kurojiru has some positive effects on tomato growth in soil-less systems.

Published
2021
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46. Microemulsion-based gel for the transdermal delivery of rasagiline mesylate: In vitro and in vivo assessment for Parkinson’s therapy

Author

Yogeshvar N. Kalia, Vandana B. Patravale, Dhaval R. Kalaria, Anuradha Pol, Pratikkumar Patel, and Abhijit A. Date

Subjects
Male, Monoamine Oxidase Inhibitors, Administration, Oral, Biological Availability, Pharmaceutical Science, 02 engineering and technology, Pharmacology, Administration, Cutaneous, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, In vivo, Rotenone, medicine, Animals, Humans, Parkinson Disease, Secondary, Skin, Skin Tests, Transdermal, business.industry, Parkinsonism, Transdermal route, Hydrogels, General Medicine, Permeation, 021001 nanoscience & nanotechnology, medicine.disease, Rats, Bioavailability, Disease Models, Animal, Biopharmaceutical, Indans, Feasibility Studies, Emulsions, Rabbits, Monoamine oxidase B, 0210 nano-technology, business, Locomotion, Biotechnology
Abstract

Rasagiline mesylate (RSM) is a selective and irreversible monoamine oxidase B inhibitor used for the treatment of Parkinson’s disease (PD). However, its unfavorable biopharmaceutical properties, such as extensive degradation in the gastrointestinal tract and first-pass metabolism are responsible for its low oral bioavailability and suboptimal therapeutic efficacy. Here, we report the feasibility of delivering RSM via the transdermal route using RSM containing microemulsion-based gel (RSM-MEG) to achieve effective management of PD. Our in vitro skin permeation studies of RSM-MEG showed significantly higher (at least ~1.5-fold) permeation across rat skin compared to the conventional RSM hydrogel. Our skin irritation studies in rabbits showed that RSM-MEG is safe for transdermal application. Finally, using the rat model of rotenone-induced Parkinsonism, we demonstrated that the topical application of RSM-MEG was equally effective in reversing PD symptoms when compared to oral RSM therapy. Thus, our study confirmed the feasibility and potential of transdermal delivery of RSM via simple topical application of RSM-MEG, and this approach could be an alternative therapeutic intervention for the treatment of Parkinson’s disease.

Published
2021
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47. CRVO IN PEDIATRIC AGE GROUP: A RARE MANIFESTATION IN KIKUCHI DISEASE

Author

Shah Neha Hemendra, Purva Date, and Anamika Agrawal

Subjects
Cultural Studies, History, Literature and Literary Theory, Process Chemistry and Technology, General Arts and Humanities, Ocean Engineering, Transportation, General Medicine, Education, Gender Studies, General Earth and Planetary Sciences, Engineering (miscellaneous), Social Sciences (miscellaneous), Water Science and Technology, General Environmental Science
Abstract

Introduction: Kikuchi Fujimoto is a rare necrotizing lymphadenitis disease. We report a case of a 17-year-old boy, known case of Kikuchi Fujimoto disease (KFD), who developed left eye central retinal vein occlusion (CRVO). A 17-year-old boy presented with left Case Presentation: eye sudden diminution of vision. He was diagnosed with Kikuchi Fujimoto necrotizing lymphadenitis disease 2 years back. He had left eye central retinal vein occlusion with disc and macular edema. Optical coherence tomography (OCT) showed subretinal uid, cystoid macular edema along with disc elevation. He was on s Hydroxychloroquine since 6 months. After systemic evaluation he was started on oral prednisolone 40mg on weekly 10mg tapering dose. After a month his macular edema as well as disc edema had signicantly resolved. KFD is itself is a rare Conclusion: entity and additional manifestation of CRVO in them, makes it rarest of rare presentation. If not diagnosed on time and treated can lead to permanent vision loss

Published
2023
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48. RIFM fragrance ingredient safety assessment, allyl phenoxyacetate, CAS Registry Number 7493-74-5

Author

A.M. Api, D. Belsito, D. Botelho, M. Bruze, G.A. Burton, null Cancellieri, H. Chon, M.L. Dagli, M. Date, W. Dekant, C. Deodhar, A.D. Fryer, L. Jones, K. Joshi, M. Kumar, A. Lapczynski, M. Lavelle, I. Lee, D.C. Liebler, H. Moustakas, M. Na, T.M. Penning, G. Ritacco, J. Romine, N. Sadekar, T.W. Schultz, D. Selechnik, F. Siddiqi, I.G. Sipes, G. Sullivan, Y. Thakkar, and Y. Tokura

Subjects
Odorants, TOXICOLOGIA AMBIENTAL, General Medicine, Registries, Toxicology, Food Science, Perfume, Glycolates
Published
2022

49. Wnt2b and Wnt5a expression is highly associated with M2 TAMs in non‑small cell lung cancer

Author

Ryota, Sumitomo, Cheng-Long, Huang, Hidenori, Ando, Tatsuhiro, Ishida, Hiroyuki, Cho, and Hiroshi, Date

Subjects
Wnt Proteins, Cancer Research, Ki-67 Antigen, Lung Neoplasms, Oncology, Carcinoma, Non-Small-Cell Lung, Tumor-Associated Macrophages, Humans, General Medicine, Immunohistochemistry, Wnt-5a Protein, Glycoproteins
Abstract

Tumor‑associated macrophages (TAMs), particularly M2 macrophages, promote tumor progression, while

Published
2022
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50. Age is a major determinant for poor prognosis in patients with pilocytic astrocytoma: a SEER population study

Author

Yusuke Tomita, Elizabeth A. Hibler, Yasuki Suruga, Joji Ishida, Kentaro Fujii, Kaishi Satomi, Koichi Ichimura, Nobuyuki Hirotsune, Isao Date, Yoshihiro Tanaka, and Yoshihiro Otani

Subjects
General Medicine, General Biochemistry, Genetics and Molecular Biology
Abstract

Background Pilocytic astrocytomas (PAs) are central nervous system tumors with variable prognosis and poorly understood risk factors. Little evidence exists regarding the effect of age on mortality in PA. Therefore, we conducted a thorough characterization of PA in the US. Methods We queried the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2018 to extract age-adjusted incidence rate (AAIR), age-adjusted mortality rate (AAMR), and survival data on PA. The age group comparisons for each measure varied depending on available SEER data. We compared trends in AAIR and AAMR by two age groups (children, 0-19 years; adults, 20 + years) and by sex. The cumulative incidence function and the Fine-Gray competing risk model were applied by 0-19, 20-39, 40-59, and 60 + years of age groups. Results This study included 5211 incident PA and 462 PA-specific deaths between 2000 and 2018. Trends in AAIRs and AAMRs were almost constant between 2000 and 2018. Average AAIRs had a sharp peak in 1-4 years of age groups, whereas AAMRs had a gradual peak in 80-84 years of age groups. Age groups, tumor location, and race/ethnicity were significantly associated with PA-specific death, whereas only age was associated with other cause of deaths. Conclusions Trends in AAIRs and AAMRs were constant regardless of age. PAs in older populations, especially over 60 years old, have higher incidence of death than those in younger populations.

Published
2022
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