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1. Super-enhancer switching drives a burst in gene expression at the mitosis-to-meiosis transition

Author

Maezawa, So, Sakashita, Akihiko, Yukawa, Masashi, Chen, Xiaoting, Takahashi, Kazuki, Alavattam, Kris G, Nakata, Ippo, Weirauch, Matthew T, Barski, Artem, and Namekawa, Satoshi H

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Genetics, Contraception/Reproduction, Human Genome, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Animals, Cell Differentiation, Enhancer Elements, Genetic, Gene Expression Regulation, Male, Meiosis, Mice, Inbred C57BL, Mice, Transgenic, Mitosis, Mutation, Polycomb-Group Proteins, Proto-Oncogene Proteins c-myb, Spermatogenesis, Spermatogonia, Trans-Activators, X Chromosome, Chemical Sciences, Medical and Health Sciences, Biophysics, Developmental Biology, Biological sciences, Biomedical and clinical sciences, Chemical sciences
Abstract

Owing to bursts in the expression of thousands of germline-specific genes, the testis has the most diverse and complex transcriptome of all organs. By analyzing the male germline of mice, we demonstrate that the genome-wide reorganization of super-enhancers (SEs) drives bursts in germline gene expression after the mitosis-to-meiosis transition. SE reorganization is regulated by two molecular events: the establishment of meiosis-specific SEs via A-MYB (MYBL1), a key transcription factor for germline genes, and the resolution of SEs in mitotically proliferating cells via SCML2, a germline-specific Polycomb protein required for spermatogenesis-specific gene expression. Before entry into meiosis, meiotic SEs are preprogrammed in mitotic spermatogonia to ensure the unidirectional differentiation of spermatogenesis. We identify key regulatory factors for both mitotic and meiotic enhancers, revealing a molecular logic for the concurrent activation of mitotic enhancers and suppression of meiotic enhancers in the somatic and/or mitotic proliferation phases.

Published
2020

2. Dialysis Provider and Outcomes among United States Veterans Who Transition to Dialysis.

Author

Streja, Elani, Kovesdy, Csaba Pal, Soohoo, Melissa, Obi, Yoshitsugu, Rhee, Connie M, Park, Christina, Chen, Joline LT, Nakata, Tracy, Nguyen, Danh V, Amin, Alpesh N, Jacobsen, Steven J, Sim, John J, and Kalantar-Zadeh, Kamyar

Subjects
Humans, Kidney Failure, Chronic, Treatment Outcome, Hospitalization, Patient Transfer, Renal Dialysis, Retrospective Studies, United States Department of Veterans Affairs, Aged, United States, Female, Male, Veterans Health, Comorbidity, Dialysis Initiation, Dialysis Provider, Incidence, Odds Ratio, Risk, Veterans, glomerular filtration rate, hospitalization, mortality, renal dialysis, Kidney Failure, Chronic, Urology & Nephrology, Clinical Sciences
Abstract

Background and objectivesVeterans with ESKD initiate dialysis under the Veterans Health Administration (VHA), an integrated health system, or are outsourced to non-VHA providers. It is unknown whether outcomes differ according to their dialysis provider at initiation. We sought to evaluate the association between dialysis provider and mortality and hospitalization among United States veterans initiating dialysis.Design, setting, participants, & measurementsAmong 68,727 United States veterans who initiated dialysis in 2007-2014, we examined the association of dialysis provider (VHA versus non-VHA) at initiation with mortality and hospitalization rates in the first 12 months post-initiation. Associations were examined across adjusted models, accounting for demographics and comorbidities.ResultsPatients were 72±11 years, 5% were women, 24% were black, and 10% (n=7584) initiated at VHA dialysis centers. VHA dialysis center patients were younger, more likely to be black, had fewer cardiovascular comorbidities, and lower eGFR at dialysis initiation. VHA provider patients were more likely to be hospitalized in the first 12 months (adjusted incidence rate ratio, 1.10; 95% confidence interval, 1.07 to 1.14), but had lower all-cause mortality risk (adjusted hazard ratio, 0.87; 95% confidence interval, 0.83 to 0.93) in fully adjusted models.ConclusionsVeteran patients initiating dialysis with a VHA dialysis provider appear to have a lower mortality risk but higher hospitalization rates than veterans initiating dialysis at non-VHA dialysis units.

Published
2018

3. Dialysate Potassium and Mortality in a Prospective Hemodialysis Cohort

Author

Ferrey, Antoney, You, Amy S, Kovesdy, Csaba P, Nakata, Tracy, Veliz, Mary, Nguyen, Danh V, Kalantar-Zadeh, Kamyar, and Rhee, Connie M

Subjects
Kidney Disease, Bioengineering, Clinical Research, Assistive Technology, Zero Hunger, Good Health and Well Being, Dialysis Solutions, Female, Humans, Kidney Failure, Chronic, Male, Middle Aged, Potassium, Prospective Studies, Renal Dialysis, Dialysate potassium, Serum potassium, Gradient, Hemodialysis, Mortality, Clinical Sciences, Urology & Nephrology
Abstract

BackgroundStudies examining the association of dialysate potassium concentration and mortality in hemodialysis patients show conflicting findings. We hypothesized that low dialysate potassium concentrations are associated with higher mortality, particularly in patients with high pre-dialysis serum potassium concentrations.MethodsWe evaluated 624 hemodialysis patients from the prospective Malnutrition, Diet, and Racial Disparities in Kidney Disease study recruited from 16 outpatient dialysis facilities over 2011-2015 who underwent protocolized collection of dialysis treatment characteristics every 6 months. We examined the association of dialysate potassium concentration, categorized as 1, 2, and 3 mEq/L, with all-cause mortality risk in the -overall cohort, and stratified by pre-dialysis serum potassium (< 5 vs. ≥5 mEq/L) using case-mix adjusted Cox models.ResultsIn baseline analyses, dialysate potassium concentrations of 1 mEq/L were associated with higher mortality, whereas concentrations of 3 mEq/L were associated with similar mortality in the overall cohort (reference: 2 mEq/L): adjusted hazard ratios (aHRs; 95% CI) 1.70 (1.01-2.88) and 0.95 (0.64-1.39), respectively. In analyses stratified by serum potassium, baseline dialysate potassium concentrations of 1 mEq/L were associated with higher mortality in patients with serum potassium ≥5 mEq/L but not in those with serum potassium < 5 mEq/L: aHRs (95% CI) 2.87 (1.51-5.46) and 0.74 (0.27-2.07), respectively (p interaction = 0.04). These findings were robust with incremental adjustment for serum potassium, potassium-binding resins, and potassium-modifying medications.ConclusionLow (1 mEq/L) dialysate potassium -concentrations were associated with higher mortality, particularly in hemodialysis patients with high pre-dialysis serum potassium. Further studies are needed to identify therapeutic strategies that mitigate inter-dialytic serum potassium accumulation and subsequent high dialysate serum potassium gradients in this population.

Published
2018

4. Intravascular large B-cell lymphoma causing hypopituitarism and respiratory failure due to infiltration into pulmonary capillaries

Author

Tatsuaki Kosaka, Yuki Honda, Yoichiro Homma, and Masanobu Nakata

Subjects
Male, Humans, General Medicine, Lymphoma, Large B-Cell, Diffuse, Respiratory Insufficiency, Lung, Hypopituitarism, Capillaries
Abstract

We report a rare case of intravascular large B-cell lymphoma (IVLBCL) with hypopituitarism and respiratory failure. A man in his 80s presented with hypotension and respiratory failure but was unsuccessfully treated for septic shock. Biological investigations were performed, and he was diagnosed with hypopituitarism due to insufficient secretion of anterior pituitary hormone. Although his condition temporarily improved following hormone replacement therapy, he eventually died of progressive respiratory failure. The lymphoma was only discovered during the autopsy, where it was observed to have spread to the pituitary gland and lung capillaries. Therefore, we concluded that the lymphoma had caused respiratory failure and hypopituitarism. The patient was thus diagnosed with IVLBCL posthumously. In conclusion, IVLBCL can cause hypopituitarism and respiratory failure due to pituitary and pulmonary capillary invasion by lymphoma cells.

Published
2024

5. Thyroid Status and Mortality in a Prospective Hemodialysis Cohort.

Author

Rhee, Connie M, You, Amy S, Nguyen, Danh V, Brunelli, Steven M, Budoff, Matthew J, Streja, Elani, Nakata, Tracy, Kovesdy, Csaba P, Brent, Gregory A, and Kalantar-Zadeh, Kamyar

Subjects
Humans, Kidney Failure, Chronic, Cardiovascular Diseases, Hypothyroidism, Thyrotropin, Renal Dialysis, Mortality, Cause of Death, Logistic Models, Proportional Hazards Models, Risk Factors, Prospective Studies, Adult, Aged, Middle Aged, California, Female, Male, Prevention, Kidney Disease, Clinical Research, Cardiovascular, Metabolic and endocrine, Good Health and Well Being, Clinical Sciences, Paediatrics and Reproductive Medicine, Endocrinology & Metabolism
Abstract

Context and objectiveCompared with the general population, hemodialysis patients have a substantially higher risk of hypothyroidism, as defined by an elevated serum thyrotropin (TSH) level, and cardiovascular mortality. Whereas an elevated TSH is associated with cardiovascular disease and death in the general population, associations among dialysis patients have been inconsistent.Design, setting, participants, and main outcomeWe examined 541 hemodialysis patients from 17 southern California dialysis centers in the prospective Hypothyroidism, Cardiovascular Health, and Survival study who underwent protocolized measurement of repeated serum TSH levels every 6 months from 2013 to 2015. Associations between TSH tertiles (

Published
2017

6. Workplace psychosocial and organizational factors for neck pain in workers in the United States

Author

Yang, Haiou, Hitchcock, Edward, Haldeman, Scott, Swanson, Naomi, Lu, Ming-Lun, Choi, BongKyoo, Nakata, Akinori, and Baker, Dean

Subjects
Allied Health and Rehabilitation Science, Commerce, Management, Tourism and Services, Human Resources and Industrial Relations, Health Sciences, Pain Research, Clinical Research, Chronic Pain, Dental/Oral and Craniofacial Disease, Prevention, Musculoskeletal, Adult, Female, Health Surveys, Humans, Male, Middle Aged, Neck Pain, Occupational Diseases, Occupational Health, Occupations, Risk Factors, United States, Work-Life Balance, Workload, Workplace, Young Adult, neck pain, occupational health, psychosocial risk factors, work organization, epidemiology, Public Health and Health Services, Environmental & Occupational Health, Human resources and industrial relations, Epidemiology, Public health
Abstract

BackgroundNeck pain is a prevalent musculoskeletal condition among workers in the United States. This study explores a set of workplace psychosocial and organization-related factors for neck pain.MethodsData used for this study come from the 2010 National Health Interview Survey which provides a representative sample of the US population. To account for the complex sampling design, the Taylor linearized variance estimation method was used. Logistic regression models were constructed to measure the associations.ResultsThis study demonstrated significant associations between neck pain and a set of workplace risk factors, including work-family imbalance, exposure to a hostile work environment and job insecurity, non-standard work arrangements, multiple jobs, and long work hours.ConclusionWorkers with neck pain may benefit from intervention programs that address issues related to these workplace risk factors. Future studies exploring both psychosocial risk factors and physical risk factors with a longitudinal design will be important. Am. J. Ind. Med. 59:549-560, 2016. © 2016 Wiley Periodicals, Inc.

Published
2016

7. Angioscopic findings 1 year after percutaneous coronary intervention for chronic total occlusion

Author

Isamu, Fukuizumi, Yukichi, Tokita, Reiko, Shiomura, Satsuki, Noma, Junya, Matsuda, Hideto, Sangen, Yoshiaki, Kubota, Hidenori, Komiyama, Jun, Nakata, Hideki, Miyachi, Shuhei, Tara, Wataru, Shimizu, Takeshi, Yamamoto, and Hitoshi, Takano

Subjects
Male, Coronary Thrombosis, Middle Aged, Angioscopy, Coronary Angiography, Percutaneous Coronary Intervention, Treatment Outcome, Coronary Occlusion, Neointima, Chronic Disease, Humans, Female, Cardiology and Cardiovascular Medicine, Aged, Retrospective Studies
Abstract

Chronic total occlusion (CTO) is a high-risk factor for stent thrombosis, but little is known about the difference in neointimal healing between CTO and non-CTO lesions regarding implanted stents. We investigated factors affecting neointimal healing after stent implantation for CTO and non-CTO lesions using angioscopy.We retrospectively evaluated 106 stents in 85 consecutive patients between March 2016 and July 2020. Their average age was 68 ± 11 years, and participants (73 male and 12 female) underwent follow-up angiography and angioscopy 1 year after percutaneous coronary intervention (PCI). The stents (n = 106) were divided into three groups according to the lesion status at the previous PCI: CTO (n = 17), acute coronary syndrome (ACS) (n = 35), and stable coronary artery disease without CTO or non-CTO (n = 54).The neointimal stent coverage grade was significantly lower in the CTO and ACS groups than in the non-CTO group (0.4 ± 0.5, 0.9 ± 0.8, and 1.4 ± 0.8, respectively, p 0.001). Thrombi were significantly more frequent in CTO and ACS than in non-CTO (71 %, 51 %, and 15 %, respectively, p 0.001). The yellow grade in CTO was comparable to that in ACS but significantly higher in CTO than in non-CTO (CTO vs. ACS vs. non-CTO 1.5 ± 0.7, 1.4 ± 0.6, and 0.9 ± 0.7, respectively, p = 0.007).Delayed healing occurs in stents implanted for CTO lesions. Longer dual-antithrombotic therapy may be beneficial.

Published
2023

8. Genetic variants on chromosome 1q41 influence ocular axial length and high myopia.

Author

Fan, Qiao, Barathi, Veluchamy, Cheng, Ching-Yu, Zhou, Xin, Meguro, Akira, Nakata, Isao, Khor, Chiea-Chuen, Goh, Liang-Kee, Li, Yi-Ju, Lim, Wane, Ho, Candice, Hawthorne, Felicia, Zheng, Yingfeng, Chua, Daniel, Inoko, Hidetoshi, Yamashiro, Kenji, Ohno-Matsui, Kyoko, Matsuo, Keitaro, Matsuda, Fumihiko, Vithana, Eranga, Mizuki, Nobuhisa, Beuerman, Roger, Tai, E-Shyong, Yoshimura, Nagahisa, Aung, Tin, Young, Terri, Wong, Tien-Yin, Teo, Yik-Ying, Saw, Seang-Mei, and Seielstad, Mark

Subjects
Adult, Animals, Carrier Proteins, Cation Transport Proteins, Child, China, Chromosomes, Human, Pair 1, Disease Models, Animal, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Lysophospholipase, Male, Mice, Middle Aged, Myopia, Nuclear Proteins, Polymorphism, Single Nucleotide, RNA-Binding Proteins, Retina, Retinal Pigment Epithelium, Sclera, Zinc Transporter 8
Abstract

As one of the leading causes of visual impairment and blindness, myopia poses a significant public health burden in Asia. The primary determinant of myopia is an elongated ocular axial length (AL). Here we report a meta-analysis of three genome-wide association studies on AL conducted in 1,860 Chinese adults, 929 Chinese children, and 2,155 Malay adults. We identified a genetic locus on chromosome 1q41 harboring the zinc-finger 11B pseudogene ZC3H11B showing genome-wide significant association with AL variation (rs4373767, β = -0.16 mm per minor allele, P(meta) =2.69 × 10(-10)). The minor C allele of rs4373767 was also observed to significantly associate with decreased susceptibility to high myopia (per-allele odds ratio (OR) =0.75, 95% CI: 0.68-0.84, P(meta) =4.38 × 10(-7)) in 1,118 highly myopic cases and 5,433 controls. ZC3H11B and two neighboring genes SLC30A10 and LYPLAL1 were expressed in the human neural retina, retinal pigment epithelium, and sclera. In an experimental myopia mouse model, we observed significant alterations to gene and protein expression in the retina and sclera of the unilateral induced myopic eyes for the murine genes ZC3H11A, SLC30A10, and LYPLAL1. This supports the likely role of genetic variants at chromosome 1q41 in influencing AL variation and high myopia.

Published
2012

9. Imaging characteristics of hypertrophic pachymeningitis due to ANCA-associated vasculitis

Author

Taro Takagi, Masahiro Okada, Masashi Nakamura, Takahiro Hanari, Takahiro Nakata, Masato Teraoka, and Naohito Hato

Subjects
Male, Otorhinolaryngology, Facial Paralysis, Humans, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Female, Meningitis, Surgery, Hypertrophy, General Medicine, Mastoiditis, Antibodies, Antineutrophil Cytoplasmic, Retrospective Studies
Abstract

Hypertrophic pachymeningitis (HP) is a rare disorder that causes localized or diffuse inflammatory fibrosis and thickening of the dura mater. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)-related HP is the most frequent form of HP. Otitis media with AAV (OMAAV) patients with HP are associated with higher rates of both ANCA-negative phenotypes and disease-related mortality. However, few studies have reported the imaging characteristics of HP due to AAV/OMAAV. Therefore, we investigated this issue in the present study.This retrospective study included patients diagnosed with HP between 2011 and 2020 at our hospital. Age, sex, causative disease, serum C-reactive protein (CRP) level, and MRI data were collected from medical records. We compared the locations of MRI enhancement depending on the causative diseases.Of the 18 included patients with HP (mean age, 64.1 ± 2.6 years; range, 33-77 years), 10 (55.6%) were female, 12 (66.7%) were diagnosed with AAV/OMAAV, four (22.2%) were diagnosed as idiopathic, two (11.1%) were diagnosed with invasive Aspergillus mastoiditis. Eleven (61.1%) had cranial neuropathies. Facial nerve paralysis was common in AAV/OMAAV, while abducent nerve paralysis was common in idiopathic HP. Cranial fossa enhancement was most common presentation in patients with HP, whereas inner acoustic canal (IAC) enhancement was seen only in patients with AAV/OMAAV, while HP involving the cavernous sinus was seen only in patients with idiopathic and mastoiditis.HP involving the IAC may be a key factor in diagnosing AAV/OMAAV.

Published
2022

10. The counteracting effect of the friction moment against the tibial rotational moment driven by the ground reaction force in an early stance phase of cutting maneuver among healthy male athletes

Author

Issei Ogasawara, Megumi Nambo, Yuki Uno, Gajanan S. Revankar, Kaho Umegaki, Haotian Cheng, Shoji Konda, Tomoyuki Matsuo, Tatsuo Mae, Ken Hashizume, and Ken Nakata

Subjects
Male, Knee Joint, Friction, Tibia, Athletes, Anterior Cruciate Ligament Injuries, Humans, Physical Therapy, Sports Therapy and Rehabilitation, Orthopedics and Sports Medicine, Anterior Cruciate Ligament, Biomechanical Phenomena
Abstract

The ground reaction force (GRF) is known to produce tibial internal rotation loading associated with the stress in the anterior cruciate ligament (ACL). However, it is unclear whether the friction moment (FM; the moment due to horizontal shoe-floor friction, acting around the vertical axis at the GRF acting point) facilitates or restrains the effect of GRF-driven tibial rotation loading during cutting. The 45° cutting motions with forefoot/rearfoot strikes were captured simultaneously with GRF and FM data from 23 healthy males. The FM- and GRF-driven tibial rotation moments were calculated. Time-series correlation between FM- and GRF-driven tibial rotation moments and the orientation relationship among those moment vectors was investigated. The FM-driven tibial rotation moment negatively correlated with the GRF-driven one within the first 10% of stance phase. The peak regression slope value was -0.34 [SD 0.33] for forefoot and -1.64 [SD 1.76] for rearfoot strikes, showing significant difference from zero (SPM one-sample t-test, p0.05). The FM-driven tibial "external" rotation moment counteracted the GRF-driven tibial "internal" rotation moment within first 10% of the stance phase in most trials, suggesting that the FM-driven tibial rotation moment potentially diminishes the effect of GRF-driven one and may reduce ACL injury risk during cutting.

Published
2022

11. Spontaneous intranasal tumours in degus ( Octodon degus ): 20 cases (2007‐2020)

Author

M, Nakata, Miwa, C C, Wu, J K, Chambers, K, Uchida, Shiga, H, Nakayama, and Sasaki

Subjects
Male, Diagnosis, Differential, Rodent Diseases, Neoplasms, Animals, Female, Nasal Cavity, Small Animals, Octodon, Retrospective Studies
Abstract

The objective of this retrospective study was to describe the clinical and histopathological findings associated with intranasal tumours in degus.Medical records of degus diagnosed with intranasal neoplasms on histopathological examination between the years 2007 and 2020 at one hospital were included in the study.Twenty degus (10 males and 10 females) were eligible for inclusion. Initial clinical signs included sneezing, abnormal nasal sounds, and nasal discharge, followed by anorexia and frequent nose rubbing. On radiography, 15 out of 20 animals showed space-occupying lesions in the nasal cavity. CT was performed in 16 animals and revealed various degrees of changes, including abnormal radiopacity within the nasal cavity and damaged nasal septum. Rhinostomy and excisional biopsy was performed in all 20 animals. Six out of 20 patients died during the perioperative period. Six and seven degus survived for 3 months and 1 year, respectively. One animal was lost to follow-up. In 16 cases the histological diagnosis was consistent with fibromas, while in 4 cases with osteomas.Intranasal neoplasms in degus are mostly benign mesenchymal tumours with various degrees of bone formation, which is unique to this animal species. This occurrence should be considered as an important differential diagnosis for upper respiratory tract disease in degus.

Published
2022

12. Treatment of atrial tachycardia arising after superior transseptal approach mitral valve surgery: Insights from ultra‐high‐density mapping to prevent atrioventricular block

Author

Satoshi Hara, Shigeki Kusa, Naoyuki Miwa, Hidenori Hirano, Tadanori Nakata, Junichi Doi, Yun Teng, Yoshikazu Satoh, Kazuya Yamao, and Hitoshi Hachiya

Subjects
Male, Arrhythmias, Cardiac, General Medicine, Treatment Outcome, Tachycardia, Catheter Ablation, Tachycardia, Supraventricular, Humans, Mitral Valve, Atrioventricular Block, Electrophysiologic Techniques, Cardiac, Cardiology and Cardiovascular Medicine, Aged, Retrospective Studies
Abstract

Mitral valve surgery employing a superior transseptal approach (STA) is associated with arrhythmogenicity and intra-atrial conduction delay, despite being optimal for visualization of the surgical field. It is sometimes difficult to treat atrial tachycardias (AT) that arise after STA. To investigate AT circuits that arise after STA in detail in order to identify the optimal ablation line, using ultra-high-resolution mapping (UHRM).We retrospectively analyzed 12 AT from 10 patients (median age 70 years, nine males) who had undergone STA surgery. The tachycardias were mapped using the Rhythmia mapping system (Boston Scientific, Natick, Massachusetts).The 12 STA-related AT (STA-AT) circuits were classifiable as follows according to location of the optimal ablation line: (1) peri-septal incision STA-AT (n = 3), (2) cavotricuspid isthmus (CTI) dependent STA-AT (n = 7), and (3) biatrial tachycardia (n = 2). Radiofrequency (RF) application terminated 11 of the 12 STA-AT. We found that difference in STA-AT circuit type was due to characteristics of the septal incision line made for STA. UHRM was important in identifying optimal ablation sites that did not create additional conduction disturbances in the right atrium (RA).ATs after STA involve complex arrhythmia circuits due to multiple and long incision lines in the RA. Accurate understanding of the arrhythmia circuit and sinus conduction in the RA after STA is recommended for treating post-surgical tachycardia in a minimally invasive manner.

Published
2022

13. Three-dimensional analysis and in vivo imaging for sperm release and transport in the murine seminiferous tubule

Author

Yuta Kanazawa, Takuya Omotehara, Hiroki Nakata, Tsuyoshi Hirashima, and Masahiro Itoh

Subjects
Male, Microscopy, Embryology, Rete Testis, Sertoli Cells, Microfluidics, Obstetrics and Gynecology, Cell Biology, Seminiferous Tubules, Spermatozoa, Mice, Imaging, Three-Dimensional, Seminiferous Epithelium, Endocrinology, Reproductive Medicine, Testis, Animals, Rheology
Abstract

In Brief Spermatozoa are released from Sertoli cells and flow in the seminiferous tubule to the rete testis. Our results suggest that the luminal flow in the tubules is repeatedly reversed and that this physical force helps spermatozoa release from the Sertoli cells. Abstract Spermatozoa released from Sertoli cells must be transported to the epididymis. However, the mechanism of the luminal flow in seminiferous tubules has remained unclear to date. Therefore, in this study, we investigated luminal flow and movements in the seminiferous tubules by three-dimensional analysis and in vivo imaging. Serial 5-μm-thick mouse testicular sections at 50-µm-intervals were prepared and stained by Periodic Acid-Schiff-hematoxylin. After three-dimensional reconstruction of the seminiferous tubules, the localization of the released spermatozoa and the stages observed in the sections were recorded in each reconstructed tubule. Luminal movements in the seminiferous tubules were observed by in vivo imaging using a fluorescent-reporter mouse and two-photon excitation microscopy system. Spermatozoa without contact to the seminiferous epithelium were not accumulated toward the rete testis. Additionally, such spermatozoa were found on their way not only to the most proximal rete testis but also a more distant rete testis from any stage VIII seminiferous epithelia. In vivo imaging demonstrated that the direction of the flagella of spermatozoa attached to the seminiferous epithelium was repeatedly reversed. The epithelium at the inner curve of the seminiferous tubule was shaken more actively and had fewer spermatozoa attached compared with the epithelium at the outer curve. Our results hence suggest that the luminal flow in the seminiferous tubules is repeatedly reversed and that this physical force helps spermatozoa to be released from Sertoli cells.

Published
2022

14. Acute encephalopathy with biphasic seizures and late reduced diffusion: Predictive EEG findings

Author

Atsuko Ohno, Akihisa Okumura, Tatsuya Fukasawa, Tomohiko Nakata, Motomasa Suzuki, Masaharu Tanaka, Yu Okai, Yuji Ito, Hiroyuki Yamamoto, Takeshi Tsuji, Hiroyuki Kidokoro, Shinji Saitoh, and Jun Natsume

Subjects
Male, Epilepsy, Infant, Electroencephalography, General Medicine, Prognosis, Brain Waves, Seizures, Febrile, Diagnosis, Differential, Status Epilepticus, Developmental Neuroscience, Child, Preschool, Acute Disease, Pediatrics, Perinatology and Child Health, Humans, Female, Neurology (clinical)
Abstract

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a common type of acute encephalopathy in Japan; the condition is clinically characterized by prolonged seizures as the initial neurological symptom, followed by late seizures 4-6 days later. It is difficult to differentiate AESD from prolonged febrile seizures (PFSs). Here, we explored the use of electroencephalography to differentiate AESD from PFSs.We studied the electroencephalograms (EEGs) of children6 years of age diagnosed with AESD or PFSs; all EEGs were recorded within 48 h of seizure onset (i.e., before the late seizures of AESD). Two pediatric neurologists evaluated all EEGs, focusing on the basic rhythm, slowing during wakefulness/arousal by stimuli, spindles, fast waves, and slowing during sleep.The EEGs of 14 children with AESD and 31 children with PFSs were evaluated. Spindles were more commonly reduced or absent in children with AESD than in those with PFSs (71% vs. 31%, p = 0.021). Fast waves were also more commonly reduced or absent in children with AESD (21% vs. 0%, p = 0.030). The rates of all types of slowing did not differ between children with AESD and those with PFSs, but continuous or frequent slowing during sleep was more common in the former (50% vs. 17%, p = 0.035).EEG findings may usefully differentiate AESD from PFSs. Reduced or absent spindles/fast waves and continuous or frequent slowing during sleep are suggestive of AESD in children with prolonged seizures associated with fever.

Published
2022

15. Extensive (subtotal) distal pancreatectomy for pancreatic ductal adenocarcinoma: a propensity score matched cohort study of short- and long-term outcomes compared with those of conventional distal pancreatectomy

Author

Yusuke, Watanabe, Kohei, Nakata, Yasuhisa, Mori, Noboru, Ideno, Naoki, Ikenaga, Takao, Ohtsuka, and Masafumi, Nakamura

Subjects
Cohort Studies, Male, Pancreatic Neoplasms, Pancreatectomy, Treatment Outcome, Humans, Female, Laparoscopy, Surgery, Propensity Score, Carcinoma, Pancreatic Ductal, Retrospective Studies
Abstract

Extensive distal pancreatectomy (ExDP) can transect the pancreatic parenchyma more from the right side than conventional distal pancreatectomy (CDP) can. This study aimed to evaluate the short- and long-term outcomes of ExDP for pancreatic ductal adenocarcinoma (PDAC) of the pancreatic body, located adjacent to the portal vein (PV).Medical records of 98 patients who underwent ExDP (n = 15) or CDP (n = 83) for PDAC were retrospectively reviewed. Short- and long-term outcomes of the two groups were compared. Propensity score matched analysis was additionally performed to minimize the impact of treatment allocation bias.In the total cohort, the CDP group had a significantly higher proportion of pancreatic tail lesions (P 0.01), higher proportion of males, and larger tumor size. Of the 15 patients who underwent ExDP, 11 could be matched. These differences of patients' characteristics were not observed after matching. Before and after matching, the duration of surgery, blood loss, rate of morbidity including pancreatic fistula, and postoperative course were comparable between the groups. The rate of recurrence and recurrence pattern were also not significantly different between the groups. ExDP for PDAC of the pancreatic body near the PV did not increase local or lymph node recurrence. The disease-free and overall survival did not differ between the groups.Surgical and oncological outcomes after ExDP for PDAC were acceptable and comparable to those after CDP. ExDP is a feasible procedure, and could be an option for the treatment of PDAC of the pancreatic body near PV.

Published
2022

16. Endoscopic tissue shielding with polyglycolic acid sheet, fibrin glue, and endoclip for perforation during balloon dilation for esophageal stricture after endoscopic submucosal dissection

Author

Kengo Kasuga, Hiroko Hosaka, Keigo Sato, Yuki Itoi, Ko Nakata, Yu Hashimoto, Hirohito Tanaka, Shiko Kuribayashi, and Toshio Uraoka

Subjects
Male, Treatment Outcome, Endoscopic Mucosal Resection, Esophageal Neoplasms, Esophageal Stenosis, Gastroenterology, Humans, Fibrin Tissue Adhesive, General Medicine, Dilatation, Polyglycolic Acid, Aged
Abstract

Esophageal endoscopic submucosal dissection can cause esophageal strictures. Endoscopic balloon dilation is the standard treatment for esophageal strictures, but has complications, including perforation, and sometimes requires surgery. We report a case of perforation during endoscopic balloon dilation for esophageal stricture secondary to esophageal submucosal dissection that was successfully treated conservatively. A 66-year-old man with superficial carcinoma in the upper thoracic esophagus underwent circumferential endoscopic submucosal dissection with local steroid injections. Endoscopic balloon dilation was performed weekly for esophageal stricture. However, during the sixth procedure, an attempt to increase the size of the balloon to 13.5 mm resulted in perforation. The patient was treated conservatively using polyglycolic acid sheet with fibrin glue at the perforation site, which was fixed using an endoclip. However, the esophageal stricture persisted after the perforation was closed and Endoscopic balloon dilation was carefully repeated twice weekly up to a maximum of 17 mm, and the endoscope was able to pass through, and associated symptoms improved. This report indicates that endoscopic tissue shielding using polyglycolic acid sheet with fibrin glue and endoclip to correct perforation, followed by additional endoscopic balloon dilation, is an alternative to surgery.

Published
2022

17. Autoimmune-mediated thrombocytopenia after allogeneic hematopoietic stem cell transplantation: significance of detecting reticulated platelets and glycoprotein-specific platelet autoantibodies

Author

Keigo Akuta, Kentaro Fukushima, Keiichi Nakata, Satoru Hayashi, Jun Toda, Yasuhiro Shingai, Kazuhito Tsutsumi, Tomohisa Machida, Akihisa Hino, Shinsuke Kusakabe, Yukiko Doi, Jiro Fujita, Hisashi Kato, Tetsuo Maeda, Takafumi Yokota, Yoshiaki Tomiyama, Naoki Hosen, and Hirokazu Kashiwagi

Subjects
Adult, Blood Platelets, Male, Purpura, Thrombocytopenic, Idiopathic, Adolescent, Platelet Count, Hematopoietic Stem Cell Transplantation, Platelet Membrane Glycoproteins, Hematology, Middle Aged, Postoperative Complications, Adrenal Cortex Hormones, Immunoglobulin G, Humans, Transplantation, Homologous, Female, Biomarkers, Autoantibodies
Abstract

Autoimmune hematological disorders are rare complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Diagnosis of immune thrombocytopenia (ITP) is challenging, especially after allo-HSCT, because various complications such as graft-versus-host disease, disease relapse, viral infection, thrombotic microangiopathy, and drug side effects can also cause thrombocytopenia. Assessment of reticulated platelets (RP) and plasma thrombopoietin (TPO) levels may be useful to distinguish between ITP and hypoplastic thrombocytopenia. ITP is generally characterized by an increased percentage of RP, and a normal or slightly increased plasma TPO level. We now report three cases of thrombocytopenia after allo-HSCT. RP% was elevated in these patients, as it is in primary ITP. However, in contrast to primary ITP, plasma TPO levels were high in two of three patients. Anti-αIIbβ3 and anti-GPIb/IX-specific direct IgG antibodies were detected as well, suggesting occurrence of immune-mediated platelet destruction in addition to bone marrow suppression in two patients. All three patients were successfully treated with corticosteroids and/or thrombopoietin receptor agonists (TPO-RAs). These results suggest that increased RP% and detection of glycoprotein-specific platelet autoantibodies are useful for the diagnosis of ITP after HSCT.

Published
2022

18. Surgical volume threshold to improve 3‐year survival in designated cancer care hospitals in 2004‐2012 in Japan

Author

Sumiyo Okawa, Takahiro Tabuchi, Kayo Nakata, Toshitaka Morishima, Shihoko Koyama, Satomi Odani, and Isao Miyashiro

Subjects
Adult, Aged, 80 and over, Male, Cancer Research, Hospitals, Low-Volume, Adolescent, General Medicine, Cancer Care Facilities, Middle Aged, Survival Rate, Young Adult, Japan, Oncology, Neoplasms, Odds Ratio, Humans, Female, Registries, Hospitals, High-Volume, Aged, Probability, Retrospective Studies
Abstract

In Japan, cancer care hospitals designated by the national government have a surgical volume requirement of 400 annually, which is not necessarily defined based on patient outcomes. This study aimed to estimate surgical volume thresholds that ensure optimal 3-year survival for three periods. In total, 186 965 patients who had undergone surgery for solid cancers in 66 designated cancer care hospitals in Osaka between 2004 and 2012 were examined using data from a population-based cancer registry. These hospitals were categorized by the annual surgical volume of each 50 surgeries (eg, 0-49, 50-99, and so on). Using multivariable Cox proportional hazard regression, we estimated the adjusted 3-year survival probability per surgical volume category for 2004-2006, 2007-2009, and 2010-2012. Using the joinpoint regression model that computes inflection points in a linear relationship, we estimated the points at which the trend of the association between surgical volume and survival probability changes, defining them as surgical volume thresholds. The adjusted 3-year survival ranges were 71.7%-90.0%, 68.2%-90.0%, and 79.2%-90.3% in 2004-2006, 2007-2009, and 2010-2012, respectively. The surgical volume thresholds were identified at 100-149 in 2004-2006 and 2007-2009 and 200-249 in 2010-2012. The extents of change in the adjusted 3-year survival probability per increase of 50 surgical volumes were +4.00%, +6.88%, and +1.79% points until the threshold and +0.41%, +0.30%, and +0.11% points after the threshold in 2004-2006, 2007-2009, and 2010-2012, respectively. The existing surgical volume requirements met our estimated thresholds. Surgical volume thresholds based on the association with patient survival may be used as a reference to validate the surgical volume requirement.

Published
2022

19. Verification of Effectiveness of Gonad Shielding in Female Hip Joint Radiography

Author

Saki, Nozoe, Kei, Terazaki, and Manabu, Nakata

Subjects
Male, Radiography, Radiation Protection, Ovary, Humans, Female, Hip Joint, General Medicine, Gonads
Abstract

It has been reported that the placement of protective equipment in female pelvic radiography is predominantly inadequate compared with that of male. We analyzed the actual situation of ovarian shielding by protective devices using X-ray, CT, and MR images obtained in the past, and evaluated the effectiveness of gonadal protection in female hip radiography.The ovaries were contoured in MR images and the pelvic bone was extracted by CT images. The MR/CT fusion images were created using a 3D workstation. The amount of physiological fluctuation in the ovarian location was measured. The fusion images in the ray-summation display were manually superimposed with the X-ray image, and the percentage of ovaries that could be shielded by the protective device was classified into four categories: (a) complete protection, (b) partial protection, (c) failure of protection, and (d) image retaking.The mean and maximum ovarian fluctuations were 1.1 cm and 3.9 cm in the superior and inferior directions, respectively, and 0.7 cm and 2.0 cm in the left and right directions, respectively. The percentage of ovaries shielded was 18.9% for complete protection, 58.5% for partial protection, 15.1% for inadequate protection, and 7.5% for image retaking.The effectiveness of gonadal protection is low because the protective device could not cover the entire ovary in about 80% of the female hip radiographs.

Published
2022

20. Negative-pressure wound therapy is effective for peritoneal dialysis catheter exit-site management in the early postoperative period

Author

Junichiro Nakata, Takuya Maeda, Nao Nohara, Yuki Shimizu, Shuko Nojiri, Yuka Shirotani, Toshiki Kano, Yusuke Suzuki, Hiroaki Io, and Haruna Fukuzaki

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, Period (gene), medicine.medical_treatment, Science, Peritonitis, Article, Medical research, Catheters, Indwelling, Negative-pressure wound therapy, medicine, Peritoneal dialysis catheter, Humans, Tokyo, Aged, Aged, 80 and over, Exit site, Multidisciplinary, business.industry, Middle Aged, Surgery, Treatment Outcome, Nephrology, Catheter-Related Infections, Kidney Failure, Chronic, Medicine, Female, business, Peritoneal Dialysis, Negative-Pressure Wound Therapy
Abstract

Peritoneal dialysis (PD) catheter exit-site care is critically important for the prevention of catheter-related infections (CRIs) and subsequent peritonitis. The postoperative management of the site is particularly essential because it has an open wound that is always adjacent to a PD catheter tube. This study aimed to examine the effectiveness of negative-pressure wound therapy (NPWT) for postoperative PD catheter exit sites. Thirty patients with end-stage renal disease who underwent simultaneous PD catheter insertion and exit-site formation were randomly assigned to receive NPWT (NPWT group) or conventional dressing (non-NPWT group) for the first seven postoperative days. The exit-site scores on the seventh postoperative day was lower in the NPWT group than in the non-NPWT group (p = 0.0049). Analysis of variance F statistic for the effect of NPWT over 180 days was highly significant (11.482595, p = 0.007). There were no statistically significant differences between the time to first CRI and PD-related peritonitis between the two groups. There was one case of CRI with relapsing peritonitis and catheter loss in the non-NPWT group. These findings demonstrate the association between NPWT and low exit-site score. NPWT can be recommended for the management of PD catheter exit sites in the early postoperative period.

Published
2022

21. Incidence and relative risk of metachronous second primary cancers for 16 cancer sites, Osaka, Japan, 2000–2015: Population‐based analysis

Author

Isao Miyashiro, Haruka Kudo, Satomi Odani, Yoshihiro Kuwabara, Toshitaka Morishima, Kayo Nakata, Takahiro Tabuchi, Shihoko Koyama, and Mizuki Kato

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Adolescent, Population, cumulative risk, Young Adult, Age Distribution, Japan, Risk Factors, Internal medicine, Epidemiology, medicine, Humans, Radiology, Nuclear Medicine and imaging, Registries, Sex Distribution, education, multiple primary cancers, Research Articles, RC254-282, Aged, Retrospective Studies, alcohol‐related cancer, education.field_of_study, business.industry, Incidence, Incidence (epidemiology), incidence rate, Absolute risk reduction, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cancer, Neoplasms, Second Primary, Middle Aged, medicine.disease, Cancer registry, Standardized mortality ratio, Oncology, Relative risk, Female, epidemiology, smoking‐related cancer, standardized incidence ratio, business, Cancer Prevention, Research Article
Abstract

Background An increasing number of cancer survivors have developed multiple primaries. This study aims to describe the incidence and risk patterns of metachronous second primary cancers (SPCs) in Osaka, Japan. Methods Data were obtained from the Osaka Cancer Registry, a population‐based database of all cancers diagnosed in Osaka. The study subjects were individuals who were first diagnosed with invasive cancers in 16 major cancer sites during 2000–2014, aged 15–79 years, survived at least 3 months, and were followed up for 10 years. We measured incidence rates, cumulative risks, and standardized incidence ratios (SIRs: with the Osaka general population as the referent) of developing SPCs during 3 months to 10 years after the first diagnosis. Results During 2000–2015, among 418,791 cancer survivors, 24,368 (5.8%) developed SPCs within 10 years of first diagnosis. Males had higher incidence rates than females except among young‐onset survivors (aged 15–39 years). 10‐year cumulative risks among survivors aged 70–79 years (the most dominant age group) were 24.0% (male) and 11.8% (female). 10‐year SIRs were 1.38 (95% CI, 1.36–1.40; male) and 1.44 (95% CI, 1.41–1.48; female) with higher estimates among younger survivors in both sexes. Strong bidirectional associations were observed between oral/pharyngeal, esophageal, and laryngeal cancers. Survivors of any smoking‐related cancers had elevated SIRs of developing smoking‐related SPCs. Similar results were observed for alcohol‐related cancers. Conclusions Cancer survivors are at excess risk of developing SPCs compared to the general population. Continued surveillance is warranted to inform survivorship care through risk‐based long‐term care planning and lifestyle‐changing efforts to prevent new cancers., During 2000–2015, 5.8% of cancer survivors in Osaka, Japan, developed metachronous second primary cancers (SPCs) within 10 years of first diagnosis. Cancer survivors were at 1.38 times (male) and 1.44 times (female) higher risks of developing SPCs compared to the general population. Coordinated efforts of survivorship care through risk‐based care planning, surveillance, and lifestyle‐changing interventions are warranted.

Published
2021

22. Human papillomavirus detected in sperm of Japanese infertile males affects reproductive parameters

Author

Masashi Iijima, Yoshifumi Kadono, Kouji Izumi, Shohei Kawaguchi, Yuki Kato, Hiroki Nakata, Kazuyoshi Shigehara, Kazufumi Nakashima, Tomomi Nakagawa, and Atsushi Mizokami

Subjects
Microbiology (medical), Male, HPV, Sperm infection, Prevalence, Semen, Infectious and parasitic diseases, RC109-216, Alphapapillomavirus, Infertile men, law.invention, Superoxide dismutase, Andrology, Japan, law, medicine, Humans, Papillomaviridae, Sperm motility, Polymerase chain reaction, biology, urogenital system, Papillomavirus Infections, HPV infection, virus diseases, General Medicine, medicine.disease, Sperm, Spermatozoa, female genital diseases and pregnancy complications, Sperm concentration, Infectious Diseases, biology.protein, Reproductive parameters, Nested polymerase chain reaction
Abstract

Objectives The effects of human papillomavirus (HPV) infection on male reproductive parameters are currently a matter of controversy. In order to clarify the issue in Japanese infertile men, the prevalence and localization of HPV in semen, sperm parameters, and superoxide dismutase (SOD) activity in seminal plasma were examined in 216 Japanese infertile men. Methods DNA was extracted from liquid-based cytological semen samples. The β-globin gene was amplified by polymerase chain reaction (PCR), and HPV-DNA was amplified using nested PCR with MY09/MY11 as outer primers and GP5+/GP6+ as inner primers. HPV genotyping was performed in the HPV-positive samples. In addition, SOD levels in seminal plasma were analysed quantitatively. In-situ hybridization (ISH) was performed to localize HPV-DNA in sperm from HPV-positive samples. Results Any-risk and high-risk prevalence rates of HPV in semen were 12.5% and 6.9%, respectively. No significant difference in the prevalence of HPV was observed between azoospermic and non-azoospermic subjects. Among non-azoospermic patients, those with HPV detected in semen had significantly lower sperm motility and concentration compared with subjects without HPV detected in semen. SOD levels in seminal plasma were significantly higher in HPV-positive patients compared with HPV-negative patients. ISH analysis of HPV-positive samples revealed that HPV-DNA was localized to the head and mid-piece of sperm. HPV-DNA was present in the sperm of young infertile men. Conclusion HPV infection of sperm was associated with reduced sperm motility and concentration, and resulted in an increase in seminal SOD activity.

Published
2021

23. Three-dimensional morphological analysis of spermatogenesis in aged mouse testes

Author

Kazuyoshi Shigehara, Hiroaki Iwamoto, Shohei Kawaguchi, Takahiro Nohara, Yoshifumi Kadono, Suguru Kadomoto, Hiroshi Yaegashi, Kouji Izumi, Masashi Iijima, Atsushi Mizokami, Taito Nakano, and Hiroki Nakata

Subjects
Male, Aging, Urology, Science, Vacuole, Biology, Article, Male infertility, Andrology, Mice, Rete testis, Testis, medicine, Animals, Spermatogenesis, Multidisciplinary, Seminiferous Tubules, Sertoli cell, medicine.disease, Epithelium, Spermatogonia, Mice, Inbred C57BL, medicine.anatomical_structure, Tubule, Seminiferous Epithelium, Morphological analysis, Medicine, Anatomy
Abstract

Spermatogenesis, which is a continuous process from undifferentiated spermatogonia to spermatozoa in the seminiferous tubules, declines with age. To investigate changes in spermatogenesis with aging, we reconstructed the seminiferous tubules of 12 mice aged 12 to 30 months from serial sections and examined age-related and region-specific alterations in the seminiferous epithelium and spermatogenic waves in three dimensions. The basic structure of the seminiferous tubules, including the numbers of tubules, terminating points, branching points, and total tubule length, did not change with age. Age-related alterations in spermatogenesis, primarily assessed by the formation of vacuoles in Sertoli cells, were detected in the seminiferous tubules at 12 months. The proportion of altered tubule segments with impaired spermatogenesis further increased by 24 months, but remained unchanged thereafter. Altered tubule segments were preferentially distributed in tubule areas close to the rete testis and those in the center of the testis. Spermatogenic waves became shorter in length with age. These results provide a basis for examining the decline of spermatogenesis not only with aging, but also in male infertility.

Published
2021

24. Loss of GSTO2 contributes to cell growth and mitochondria function via the p38 signaling in lung squamous cell carcinoma

Author

Toru Igari, Kazuaki Nakata, Hideki T. Miyazaki, Ryusuke Sumiya, Satoshi Nagasaka, Masayoshi Terayama, Yuki I. Kawamura, Kazuhiko Yamada, Teruki Hagiwara, and Keigo Sekihara

Subjects
Male, Cancer Research, Lung Neoplasms, MAP Kinase Signaling System, LSCC, cancer metabolism, Down-Regulation, Mice, Nude, p38, Mitochondrion, Decitabine, Oxidative Phosphorylation, Epigenesis, Genetic, Alveolar cells, Mice, Downregulation and upregulation, Cell, Molecular, and Stem Cell Biology, Cell Line, Tumor, medicine, Animals, Humans, Glutathione Transferase, Chemistry, Cell growth, Liver Neoplasms, General Medicine, Original Articles, DNA Methylation, In vitro, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Oncology, Cell culture, DNA methylation, Cancer research, Carcinoma, Squamous Cell, β‐catenin, Original Article, Signal transduction, Glycolysis, Neoplasm Transplantation, GSTO2
Abstract

Glutathione S‐transferase omega 2 (GSTO2) lacks any appreciable GST activity, but it exhibits thioltransferase activity. The significance of GSTO2 in lung function has been reported; however, the precise expression and molecular function of GSTO2 in the lungs remain unclear. In the present study, we found that GSTO2 is expressed in airway basal cells, non–ciliated, columnar Clara cells, and type II alveolar cells, which have self‐renewal capacity in the lungs. Contrastingly, no GSTO2 expression was observed in 94 lung squamous cell carcinoma (LSCC) samples. When human LSCC cell lines were treated with 5‐aza‐2′‐deoxycytidine, a DNA‐methyltransferase inhibitor, GSTO2 transcription was induced, suggesting that aberrant GSTO2 hypermethylation in LSCC is the cause of its downregulation. Forced GSTO2 expression in LSCC cell lines inhibited cell growth and colony formation in vitro. In a subcutaneous xenograft model, GSTO2‐transfected cells formed smaller tumors in nude mice than mock‐transfected cells. Upon intravenous injection into nude mice, the incidence of liver metastasis was lower in mice injected with GSTO2‐transfected cells than in those injected with mock‐transfected cells. In addition, GSTO2 induction suppressed the expression of β‐catenin and the oxygen consumption rate, but it did not affect the extracellular acidification rate. Furthermore, GSTO2‐transfected cells displayed lower mitochondrial membrane potential than mock‐transfected cells. When GSTO2‐transfected cells were treated with a p38 inhibitor, β‐catenin expression and mitochondrial membrane potential were recovered. Our study indicated that the loss of GSTO2 via DNA hypermethylation contributes to the growth and progression of LSCC, probably by modulating cancer metabolism via the p38/β‐catenin signaling pathway., Glutathione S‐transferase omega 2 (GSTO2) is expressed in the stem cells of the bronchial and alveolar epithelium. Loss of GSTO2 might contribute to lung squamous cell carcinoma growth by modulating cancer metabolism via the p38/β‐catenin signaling pathway.

Published
2021

25. Trajectory of the incidence of brushes on preterm electroencephalogram and its association with neurodevelopment in extremely low birth weight infants

Author

Tetsuo Kubota, Hiroyuki Kidokoro, Akihisa Okumura, Jun Natsume, Takashi Maeda, Toru Kato, Tomohiko Nakata, Takashi Tachibana, Masahiro Hayakawa, Anna Shiraki, Yoshiaki Sato, Hiroyuki Yamamoto, and Tatsuya Fukasawa

Subjects
Male, Pediatrics, medicine.medical_specialty, Developmental Disabilities, Developmental Neuroscience, medicine, Humans, Active sleep, Developmental quotient, Brain Diseases, business.industry, Incidence (epidemiology), Infant, Newborn, Electroencephalography, General Medicine, Magnetic Resonance Imaging, White Matter, White matter abnormality, Low birth weight, Quiet sleep, Infant, Extremely Low Birth Weight, Pediatrics, Perinatology and Child Health, White matter abnormalities, Brain lesions, Female, Neurology (clinical), medicine.symptom, business, Infant, Premature
Abstract

Brush or delta brush is a well-known characteristic waveform in preterm electroencephalograms. However, the longitudinal trajectory of brushes and its association with neurodevelopment remain uncertain.We analyzed the longitudinal incidence of brushes in 36 extremely low birth weight infants without severe brain lesions and its association with neurodevelopment and white matter abnormality. Conventional eight-channel electroencephalograms were recorded at 30, 32, 36, and 40 postmenstrual weeks (PMW). Incidence of brushes was calculated as the sum of brushes from each channel separated by active sleep and quiet sleep. A developmental delay was defined as a developmental quotient of85 assessed at corrected age of 18 months. White matter abnormalities were evaluated with term-equivalent magnetic resonance imaging.The median incidence of brushes (per minute) in 36 infants at PMW 30, 32, 36, and 40 was 16.4, 20.4, 22.5, and 1.8 during active sleep and 7.5, 10.3, 11.5, and 1.7 during quiet sleep, respectively. Among the 36 infants, 14 infants were diagnosed with developmental delay. Longitudinal trajectories of the incidence of brushes were different between the normal and the delayed development groups. Brushes were observed most frequently at 36 PMW in the delayed development group. The incidence of brushes at 36 PMW was significantly correlated with the severity of white matter abnormalities and negatively correlated with the developmental quotient.The incidence of brushes at 36 PMW can be a unique predictor of early neurodevelopment in extremely low birth weight infants without severe brain lesions.

Published
2021

26. Tumor PD-L1 and VEGF Expression, and CD8 T Cell Infiltration Predict Clinical Response to Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer

Author

Katsuhiko Shimizu, Yuji Nojima, Takeshi Kurosaki, Shinsuke Saisho, Mikio Oka, Toru Oga, Koji Kurose, Masao Nakata, and Ai Maeda

Subjects
Adult, Male, Vascular Endothelial Growth Factor A, Cancer Research, Lung Neoplasms, CD8-Positive T-Lymphocytes, B7-H1 Antigen, chemistry.chemical_compound, Lymphocytes, Tumor-Infiltrating, Carcinoma, Non-Small-Cell Lung, PD-L1, Tumor Microenvironment, Humans, Medicine, Cytotoxic T cell, Lung cancer, Receptor, Immune Checkpoint Inhibitors, Aged, Aged, 80 and over, biology, business.industry, General Medicine, Middle Aged, medicine.disease, Progression-Free Survival, Vascular endothelial growth factor, Oncology, chemistry, Disease Progression, biology.protein, Cancer research, Biomarker (medicine), Immunohistochemistry, Female, business, CD8
Abstract

Background/aim We evaluated the efficacy of "the tumor immune microenvironment (TIME) classification" for predicting clinical response to immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC). In addition, we aimed to evaluate the "modified TIME classification", which adds the vascular endothelial growth factor (VEGF) status to TIME. Materials and methods Programmed cell death receptor ligand-1 (PD-L1), CD8 T cell tumor-infiltrating lymphocytes (CD8+TILs) count and VEGF expression analyses were performed using immuno - histochemistry in 44 patients who had undergone ICI monotherapy. Results Regarding TIME classification, type-I (PD-L1 high and CD8+TILs high) had a significantly higher response than the other types. Using the modified TIME classification, type-IA (PD-L1 high, CD8+TILs high, and VEGF low) had a significantly higher response than the other types. Conclusion The modified TIME classification, which adds tumor VEGF expression to "the TIME classification", could be useful in predicting clinical response to ICI monotherapy.

Published
2021

27. [Stanford Type A Acute Aortic Dissection with Myonephropathic Mrtabolic Syndrome]

Author

Koji, Okamoto, Yusuke, Nakata, Yoshiyuki, Yamashita, Kunihiko, Joo, Yoshie, Ochiai, and Shigehito, Tokunaga

Subjects
Male, Aortic Dissection, Aortic Aneurysm, Thoracic, Ischemia, Humans, Aorta, Abdominal, Syndrome, Middle Aged, Kidney, Vascular Surgical Procedures
Abstract

A 57-year-old man was transferred with sudden onset chest pain and evolving paralysis and numbness in the left leg. Contrast computed tomography (CT) revealed Stanford type A acute aortic dissection from the ascending aorta to bilateral internal and external iliac arteries with blood flow obstruction to the left kidney and left lower limb. Surgery was initiated 10 hours after onset of ischemic symptoms in the leg. Femoro-femoral bypass was carried out first, and we ensured sufficient phlebotomy from the ischemic limb during reperfusion and continuous hemodiafiltration to prevent myonephropathic metabolic syndrome. Total aortic arch replacement was then performed. Our treatment strategy was effective in this case of Stanford type A aortic dissection with prolonged lower limb ischemia. Although left hip disarticulation was subsequently required due to intractable infection, the patient became able to walk with an artificial limb after post-rehabilitation.

Published
2022

28. Effects of Longitudinal Changes in Lifestyle-Related Risk Factors on the Incidence of Major Adverse Cardiac and Cerebrovascular Disease in Young Adults

Author

Mitsuko, Nakata, Keitaro, Senoo, Miyoko, Yamaoka, Muneaki, Kumagai, Hiromi, Nishimura, Satoaki, Matoba, and Satoshi, Teramukai

Subjects
Male, Metabolic Syndrome, Young Adult, Cerebrovascular Disorders, Risk Factors, Incidence, Humans, Female, Middle Aged, Life Style
Abstract

Metabolic syndrome (MetS) is one focus of healthcare system reform in Japan. We examined the effects of changes in individual risk factors over time on the incidence of major adverse cardio-cerebrovascular events (MACCE) in adults under the age of 50 years. Study participants under the age of 50 with neither hypertension nor hyperglycemia at baseline were analyzed. We used a parametric proportional hazard model to determine the effect of changes in abdominal circumference, blood pressure, serum lipids, and blood glucose on the incidence of MACCE.A total of 6,125 women and 6,403 men were subject to the analyses. The incidence rate of MACCE per 1,000 person-years was 1.17 for women and 2.42 for men. In men under the age of 50, an increase in abdominal circumference was associated with an increase in MACCE incidence (hazard ratio per 1 cm increase: 1.10; 95% confidence interval [CI], 1.04-1.17), whereas no statistically significant association was observed in women. Compared with Visit 1, if the abdominal circumference increased by 4 cm at Visit 3, the hazard ratio for developing MACCE was approximately 1.5 (hazard ratio 1.48; 95% CI, 1.18-1.86). In men under the age of 50, increases in abdominal circumference and systolic blood pressure were associated with an increased risk of developing MACCE, regardless of the degree of obesity at baseline. Therefore, encouraging young adults to improve their health before developing MetS may reduce the risk of MACCE.

Published
2022

29. Perception of yips among professional Japanese golfers: perspectives from a network modelled approach

Author

Ken Nakata, Sadahito Kawamura, Issei Ogasawara, Noriaki Hattori, Yuta Kajiyama, Gajanan S. Revankar, Yasufumi Gon, Hideki Mochizuki, Tomohito Nakano, and Yoshikazu Ugawa

Subjects
Adult, Male, Adolescent, media_common.quotation_subject, Science, Psychological intervention, Logistic regression, Article, Odds, Young Adult, Japan, Perception, Surveys and Questionnaires, Health care, medicine, Prevalence, Humans, media_common, Aged, Multidisciplinary, High prevalence, Movement Disorders, business.industry, Middle Aged, Anxiety Disorders, Musculoskeletal problems, Neurology, Dystonic Disorders, Anxiety, Golf, Medicine, Female, Neural Networks, Computer, Self Report, medicine.symptom, business, Psychology, Health occupations, Stress, Psychological, Clinical psychology
Abstract

‘Yips’ in golf is a complex spectrum of anxiety and movement-disorder that affects competitive sporting performance. With unclear etiology and high prevalence documented in western literature, the perception and management of this psycho-neuromuscular problem among Japanese elite golfers is unknown. The objective of this study was to explore factors associated with yips, investigate the performance deficits and the strategies implemented to prevent yips. We surveyed approx. 1300 professional golfers on their golfing habits, anxiety and musculoskeletal problems, kinematic deficits, changes in training and their outcomes. Statistical procedures included multiple logistic regression and network analysis. 35% of the respondents had experienced yips in their career, their odds increasing proportionally to their golfing experience. Regardless of musculoskeletal symptoms, about 57% of all yips-golfers attributed their symptoms to psychological causes. Network analysis highlighted characteristic movement patterns, i.e. slowing, forceful or freezing of movement for putting, approach and teeing shots respectively. Golfers’ self-administered strategies to relieve yips were mostly inconsequential. Within the limits of our self-reported survey, most golfers perceived yips as a psychological phenomenon despite evidence pointing to a movement-disorder. While self-administered interventions were satisfactory at best, it may be imperative to sensitize golfers from a movement-disorder standpoint for early management of the problem.

Published
2021

30. Long-term Outcomes of Extracardiac Total Cavopulmonary Connection for Apicocaval Juxtaposition

Author

Takaya Hoashi, Tomohiro Nakata, Motoki Komori, Kenichi Kurosaki, Kenta Imai, Hajime Ichikawa, and Masatoshi Shimada

Subjects
Heart Defects, Congenital, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Time Factors, Extracardiac conduit, Total cavopulmonary connection, Superior vena, 030204 cardiovascular system & hematology, Fontan Procedure, Univentricular Heart, Inferior vena cava, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Superior vena cava, Long term outcomes, Humans, Medicine, Cineangiography, cardiovascular diseases, Retrospective Studies, business.industry, Infant, Surgery, Apex (geometry), Treatment Outcome, 030228 respiratory system, medicine.vein, Child, Preschool, cardiovascular system, Female, Cardiology and Cardiovascular Medicine, business
Abstract

The long-term outcomes of a total cavopulmonary connection (TCPC) with an extracardiac conduit (ECC) for patients with apicocaval juxtaposition (ACJ) remain unclear.A total of 38 patients with ACJ who underwent TCPC with ECC between 1998 and 2014 were enrolled in this study. For 19 patients with a superior vena cava - inferior vena cava contralateral position, a long-curved route rounding the opposite side of the apex was selected (CC group). For 11 patients with a superior vena cava-inferior vena cava ipsilateral position, a long-curved route was principally selected (IC group); however, a short, straight route was selected for 8 patients because there was sufficient space behind the ventricular apex (IS group).Follow-up was completed in all patients, with a mean follow-up duration of 13.2 ± 4.9 years. The angles of the caudal conduit anastomosis site measured from the frontal view of cineangiography had significantly straightened in the CC group from 1 year to 15 years (P.05) and in the IC group from 1 year to 10 years (P.05). There were 2 late mortalities and 6 reoperations during follow-up. Overall survival and freedom from reoperation rates at 15 years were 95% and 82%, respectively. There were no conduit-related or route-related complications such as death, reoperations, pulmonary venous obstructions, conduit obstructions, or pulmonary arteriovenous malformations in any of the groups.Even though chronologic geometric changes of curved ECCs were observed, TCPC with ECC for patients with ACJ can be safely applied without conduit- or route-related complications in long-term follow-up.

Published
2021

31. Long-term trends in the clinical outcomes of patients with acute myeloid leukemia: a population-based real-world data analysis using the Osaka Cancer Registry

Author

Isao Miyashiro, Kayo Nakata, Jun Ishikawa, Toshitaka Morishima, Shuhei Kida, and Shigeo Fuji

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Kaplan-Meier Estimate, Population based, Young Adult, Japan, Long period, Internal medicine, Humans, Medicine, Registries, Age of Onset, Mortality, Child, Aged, Aged, 80 and over, Hematology, business.industry, Infant, Newborn, Infant, Myeloid leukemia, Treatment options, General Medicine, Middle Aged, medicine.disease, Cancer registry, Leukemia, Myeloid, Acute, Leukemia, Treatment Outcome, Child, Preschool, Female, business, Real world data
Abstract

We evaluated the survival patterns for acute myeloid leukemia (AML) patients registered in the Osaka Cancer Registry from 1975 to 2017. During this period, 9706 patients were diagnosed with AML, with a median age of 60 years (range, 0–100). Patients were grouped by age (≤ 20, 21–40, 41–60, 61–70, and ≥ 71) and the year of their diagnosis (1975–1989, 1990–2001, 2002–2010, and 2011–2017). The overall survival (OS) rates of patients of ≤ 60 years of age improved significantly from the period 1975–1989 up to 1990–2001. However, there was a stagnation from 2002–2010 to 2011–2017. In terms of non-acute promyelocytic leukemia patients of > 60 years of age, the improvement of OS was limited during a very long period. In conclusion, the clinical outcome of patients with AML dramatically improved from 1975 to 2001. However, our dataset revealed stagnation in the improvement since 2002. Novel treatment options are needed to further improve the survival of elderly patients.

Published
2021

32. Analysis of nocturnal desaturation waveforms using algorithms in patients with idiopathic pulmonary fibrosis

Author

Kyosuke Nakata, Yuichiro Yasuda, Kiyonobu Takatsuki, Kayoko Okamura, Yasuhiro Funada, Yoshihiro Nishimura, Kazuyuki Kobayashi, Mina Yasuda, Masatsugu Yamamoto, Shintaro Izumi, Teruaki Nishiuma, Kosuke Tsuruno, Tatsuya Nagano, Hisashi Ohnishi, and Kazunori Tobino

Subjects
Male, medicine.medical_specialty, Neurology, Polysomnography, Percutaneous oxygen saturation, Home sleep apnea test, Idiopathic pulmonary fibrosis, Nocturnal, Hypoxemia, Sleep Apnea Syndromes, medicine, Humans, Hypoxia, business.industry, Nocturnal hypoxemia, Correction, Sleep apnea, medicine.disease, Comorbidity, Oxygen, Obstructive sleep apnea, Otorhinolaryngology, Breathing, Neurology (clinical), medicine.symptom, business, Algorithm, Algorithms
Abstract

Purpose Sleep-disordered breathing is recognized as a comorbidity in patients with idiopathic pulmonary fibrosis (IPF). Among them, nocturnal hypoxemia has been reported to be associated with poor prognosis and disease progression. We developed a diagnostic algorithm to classify nocturnal desaturation from percutaneous oxygen saturation (SpO2) waveform patterns: sustained pattern, periodic pattern, and intermittent pattern. We then investigated the prevalence of nocturnal desaturation and the association between the waveform patterns of nocturnal desaturation and clinical findings of patients with IPF. Methods We prospectively enrolled patients with IPF from seven general hospitals between April 2017 and March 2020 and measured nocturnal SpO2 and nasal airflow by using a home sleep apnea test. An algorithm was used to classify the types of nocturnal desaturation. We evaluated the association between sleep or clinical parameters and each waveform pattern of nocturnal desaturation. Results Among 60 patients (47 men) who met the eligibility criteria, there were 3 cases with the sustained pattern, 49 cases with the periodic pattern, and 41 cases with the intermittent pattern. Lowest SpO2 during sleep and total sleep time spent with SpO2 Conclusion We demonstrated the prevalence of each waveform and association between each waveform and sleep parameters in patients with IPF. This classification algorithm may be useful to predict the degree of hypoxemia or the complication of obstructive sleep apnea.

Published
2021

33. Three‐dimensional analysis of mesonephric tubules remodeling into efferent tubules in the male mouse embryo

Author

Hiroki Nakata, Masahiro Itoh, and Takuya Omotehara

Subjects
Epididymis, Male, Mesonephric tubules, endocrine system, Rete Testis, Sex Differentiation, Efferent, Efferent ducts, Embryo, Anatomy, Biology, Embryo, Mammalian, Spermatozoa, Mesonephric duct, Mice, medicine.anatomical_structure, Rete testis, Testis, medicine, Animals, Duct (anatomy), Process (anatomy), Developmental Biology
Abstract

Background Spermatozoa are transported to the epididymal duct through efferent tubules. Although the origin of the efferent tubules is thought to be mesonephric tubules, their detailed developmental process, for example, where the rete testis and efferent tubules are connected, is unclear. We investigated the structural changes of the mesonephric tubules in the male mouse embryo using a three-dimensional reconstruction method. Results Three-six mesonephric tubules were connected to the Wolffian duct, and some of them branched, resulting in five-nine tips. Rete cells contacted the three-six tips. The mesonephric tubules showed a folded shape when the gonadal fate was determined. After the testis development started, they became short and straight but emerged as long and twisting by birth. Before birth, the efferent duct was composed of mesonephric tubules and a cranial portion of the folded Wolffian duct. Conclusions The contact between the rete testis and efferent tubules is possibly established at the tip of each mesonephric tubule. The mesonephric tubules regress after gonadal fate is determined but is remodeled to the twisting efferent tubules by birth. The efferent tubules are composed of the MTs but also a cranial portion of the folded Wolffian duct in the mouse. This article is protected by copyright. All rights reserved.

Published
2021

34. Productivity Change of Surgeons During the Coronavirus Disease 2019 Pandemic in Japan

Author

Yoshinori Nakata, Yuichi Watanabe, and Akihiko Ozaki

Subjects
Male, Surgeons, Japan, Health Policy, COVID-19, Humans, Female, Efficiency, Organizational, Pandemics
Abstract

The purpose of this study is to compute surgical total factor productivity before and during the pandemic with Malmquist index, and to evaluate the effect of coronavirus disease 2019 (COVID-19) on its productivity change. The COVID-19 pandemic has significantly shifted healthcare resources allocation; more healthcare resources have focused on measures against the COVID-19 pandemic. The authors collected data from all the surgical procedures performed in Teikyo University Hospital from April 1 through September 30 in 2019 and in 2020. Non-radial and non-oriented Malmquist model under the constant return-to-scale assumptions was employed. The decision-making unit was defined as a surgeon with the highest academic rank in surgery. Inputs were defined as (1) the number of medical doctors who assisted surgery and (2) the duration of surgical operation from skin incision to closure. The output was defined as the surgical fee for each surgery. The study period was divided into four 3-month periods. We added all the inputs and outputs of the surgical procedures for each decision-making unit during these study periods, and computed his/her Malmquist index, efficiency change, and technical change. Four thousand six hundred and two surgical procedures performed by 75 surgeons were analyzed. The productivity progressed significantly during 2019 ( P = .008) while the productivity changes in 2020 were not significantly different from 0. On year-on-year comparisons, the productivity change was not significantly different from 0. The COVID-19 pandemic had a negative impact on the productivity progress of surgery that was unrelated to its countermeasures.

Published
2022

35. Auditory sensory range of male mosquitoes for the detection of female flight sound

Author

Toshiyuki Nakata, Patrício Simões, Simon M. Walker, Ian J. Russell, and Richard J. Bomphrey

Subjects
Male, Biomaterials, Culex, Culicidae, Sound, Flight, Animal, Biomedical Engineering, Biophysics, Animals, Female, Bioengineering, Biochemistry, Biotechnology
Abstract

Male mosquitoes detect and localize conspecific females by their flight-tones using the Johnston's organ (JO), which detects antennal deflections under the influence of local particle motion. Acoustic behaviours of mosquitoes and their JO physiology have been investigated extensively within the frequency domain, yet the auditory sensory range and the behaviour of males at the initiation of phonotactic flights are not well known. In this study, we predict a maximum spatial sensory envelope for flying Culex quinquefasciatus by integrating the physiological tuning response of the male JO with female aeroacoustic signatures derived from numerical simulations. Our sensory envelope predictions were tested with a behavioural assay of free-flying males responding to a female-like artificial pure tone. The minimum detectable particle velocity observed during flight tests was in good agreement with our theoretical prediction formed by the peak JO sensitivity measured in previous studies. The iso-surface describing the minimal detectable particle velocity represents the quantitative auditory sensory range of males and is directional with respect to the female body orientation. Our results illuminate the intricacy of the mating behaviour and point to the importance of observing the body orientation of flying mosquitoes to understand fully the sensory ecology of conspecific communication.

Published
2022

36. 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. 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K., Kremis E., Kruczyk D., Krzesiak-Lodyga A., Krzyzanowski M., Kurdzielewicz W., Kustrzycka-Kratochwil D., Lesniewska-Krynska D., Leszczynski J., Lewicka E., Lichota E., Lip K., Loboz-Rudnicka M., Luka J., Lysek-Jozefowicz A., Machnikowska M., Majewska K., Mariankowski R., Markiewicz A., Mazur M., Metzgier-Gumiela A., Miedlar E., Mielcarek M., Neubauer-Geryk J., Niedek J., Niemirycz-Makurat A., Nowak A., Nowak S., Opielowska-Nowak B., Ozgowicz M., Pawelska-Buczen A., Pawlik-Rak E., Piotrowicz R., Ptaszynski P., Raczynska A., Rogowski W., Romanek J., Romaszkiewicz R., Rostoff P., Roszczyk N., Rozewska-Furmanek D., Rychta J., Rzyczkowska B., Sidor A., Skalska J., Smichura M., Splawski M., Staneta P., Staniszewska E., Starak-Marciniak J., Stopyra-Poczatek M., Sukiennik-Kujawa M., Szafranski J., Szalecki P., Szczepanska A., Szkrobka W., Szuchnik E., Szulowska A., Szumczyk-Muszytowska G., Szwoch M., Traczyk T., Troszczynska M., Trzcinski G., Tybura S., Walasik P., Wegrzynowska M., Wesolowska K., Wieczorek W., Wierzbicka A., Wilczewski P., Wilgat-Szecowka M., Wojewoda P., Wojnowski L., Wrobel M., Zakutynska-Kowalczyk K., Zyczynska-Szmon M., Eltishcheva V., Libis R., Tereshchenko S., Popov S., Kamalov G., Belenky D., Zateyshchikova A., Kropacheva E., Kolesnikova A., Nikolaev K., Egorova L., Khokhlov A., Yakupov E., Poltavskaya M., Zateyshchikov D., Drapkina O., Vishnevsky A., Barbarash O., Miller O., Aleksandrova E., Chizhov P., Sergeev M., Shutemova E., Mazur E., Zrazhevskiy K., Novikova T., Kostenko V., Moiseeva Y., Polkanova E., Sobolev K., Rossovskaya M., Zubeeva G., Shapovalova Y., Nagibovich O., Edin A., Agakhanyan A., Batalov R., Belenkova Y., Bitakova F., Chugunnaya S., Dumikyan A., Erofeeva S., Gorbunova E., Gorshkova T., Gubanov A., Gurmach M., Ivanova Y., Kolesova T., Konyushenko D., Korneeva O., Kropova O., Kuchuk P., Kungurtseva O., Kupriyanova T., Kurylo B., Kuvanova M., Lebedeva O., Lileeva E., Machilskaya O., Medvedeva T., Monako G., Motylev I., Nagibovich G., Novikova E., Orlov Y., Osmolovskaya Y., Ovsannikova A., Platonov D., Rachkova S., Sinitsina O., Speshilova S., Suslova O., Ushakov A., Volodicheva O., Zemlianskaia O., Zhirov I., Zhuravleva E., Zotova I., Garcia P. 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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. B., Seamark C., Shewring J., Simmons P., Simper H., Stoddart H., Sword A., Thomas N., Thomson A., Blenkhorn A., Singh B., Van Gaal W., Abhayaratna W., Lehman R., Roberts-Thomson P., Kilian J., Coulshed D., Catanchin A., Colquhoun D., Kiat H., Eccleston D., French J., Zimmett L., Ayres B., Phan T., Blombery P., Crimmins D., O'Donnell D., Choi A., Astridge P., Arstall M., Jepson N., Binnekamp M., Lee A., Rogers J., Starmer G., Carroll P., Faunt J., Aggarwala A., Barry L., Batta C., Beveridge R., Black A., Bonner M., Boys J., Buckley E., Campo M., Carlton L., Connelly A., Conway B., Cresp D., Dimitri H., Dixon S., Dolman M., Duroux M., Eskandari M., Eslick R., Ferreira-Jardim A., Fetahovic T., Fitzpatrick D., Geraghty R., Gibbs J., Grabek T., Modi M. H., Hayes K., Hegde M. P., Hesketh L., Hoffmann B., Johnson K., Juergens C., Kassam I., Lawlor V., Lehman M., Lehman S., Leung D., Mackay S., MacKenzie M., McCarthy C., McIntosh C., McKeon L., Morrison H., Mussap C., Myers J. -D., Nagalingam V., Oldfield G., O'May V., Palmer J., Parsons L., Patching K., Patching T., Paul V., Plotz M., Preston S., Rashad H., Ratcliffe M., Raynes S., Rose J., Sanders L., Seremetkoska M., Setio H., Shone S., Shrestha P., Singh C., Singleton C., Stoyanov N., Sutcliffe S., Swaraj K., Tarrant J., Thompson S., Tsay I. M., Vorster M., Waldman A., Wallis L., Wilford E., Wong K., Luton R., Gupta M., Pandey A. S., Cheung S., Leader R., Beaudry P., Ayala-Paredes F., Berlingieri J., Heath J., Poirier G., Du Preez M., Nadeau R., Dresser G., Dhillon R., Hruczkowski T., Schweitzer B., Coutu B., Angaran P., MacDonald P., Vizel S., Fikry S., Parkash R., Lavoie A., Cha J., Ramjattan B., Bonet J., Ahmad K., Aro L., Aves T., Beaudry K., Bergeron C., Bigcanoe J., Bignell N., Breakwell L., Burke E., Carroll L., Clarke B., Cleveland T., Daheb S., Dehghani P., Denis I., Djaidani Z., Dorian P., Douglass S., Dunnigan J., Ewert A., Farquhar D., Fearon A., Ferleyko L., Fournier D., Fox B., Grenier M. -C., Gulliver W., Haveman K., Hines C., Hines K., Jackson A. M., Jean C., Jethoo G., Kahlon R., Kelly S., Kim R., Korley V., Kornder J., Kwan L., Largy J., Lewis C., Lewis S., Mangat I., Moor R., Navratil J., Neas I., Otis J., Otis R., Pandey M., Petrie F., Pinter A., Raines M., Roberts P., Robinson M., Sas G., Schulman S., Snell L., Spearson S., Stevenson J., Trahey T., Wong S., Wright D., El-Aziz A. A., Seif S. K. A., El Din M. G., El Etriby S., Elbahry A., El-Etreby A., Elkhadem M., Katta A., Khairy T., Mowafy A., Nawar M., Ohanissian A., Reda A., Reda M., Salem H., Sami N., Samir S., Setiha M., Sobhy M., Soliman A., Taha N., Tawfik M., Zaatout E., Kettles D., Bayat J., Siebert H., Horak A., Kelfkens Y., Garda R., Pillay T., Guerra M., van Zyl L., Theron H., Murray A., Louw R., Greyling D., Mntla P., Ueckermann V., Loghdey R., Ismail S., Ahmed F., Engelbrecht J., Ramdass A., Maharajh S., Oosthuysen W., Angel G., Bester C., Booysen M., Boshoff C., Cannon C., Cassimjee S., Chami C., Conway G., Davids A., de Meyer L., Du Plessis G., Ellis T., Henley L., Karsten M., Loyd E., Marks J., Mavhusa L., Mostert M., Page A., Rikhotso L., Salie M., Sasto J., Shaik F., Skein A., Smith L., Tarr G., Tau T., van Zyl F., Yousef G., Agrawal A., Nathani M., Ibrahim M., Esheiba E. 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, 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P., Prieto, I., Quintern, V., Renom, R., Diaz, L. M. R., Rios, V., Sola, L. R., Rivera, R., Robiro, X. R., Roca, M., Saumell, C. R., Rodrigo, C., Rodriguez, E., Garcia, M. R., Jimenez, S. S., Calderon, P. S., Mendez, L. S., Parra, S. S., Santolaya, C., Sanz, M. R. S., Blanco, A. S., Serralvo, E., Sierra, N., Valero, C. S., Lopez, J. S., Fontanillas, M. T., Riera, M. T., Tobajas, G., Torres, C., Marques, J. T., Pastor, M. U., Wirdby, A., Linden, J., Henriksson, K., Elmersson, M., Egilsson, A., Borjesson, U., Svard, G., Liu, B., Lindh, A., Olsson, L. -B., Gustavsson, M., Andersson, L., Benson, L., Bothin, C., Hajimirsadeghi, A., Kadir, K., Ericsson, M., Ohlsson, A., Lindvall, H., Svensson, P., Thorne, K., Handel, H., Platonov, P., Eriksson, B., Timberg, I., Romberg, K., Crisby, M., Karlsson, J. -E., Jensen, S. A., Andersson, A., Malmqvist, L., Martinsson, B., Bernsten, F., Engdahl, J., Thulin, J., Hot-Bjelac, A., Stalby, P., Aaroe, H., Ahbeck, E., Ahlmark, H., Al-Khalili, F., Bonkowski, G., Dzeletovic, S., Ekstrand, A. -B., Eriksson, G. -B., Floren, K., Grassjo, C., Hahn, S., Jaensson, P., Jansson, B., Jansson, J. -H., Kangert, R. -M., Koch, A., Kusiak, D., Lettenstrom, A., Lindberg, A., Lindholm, C. -J., Mannermyr, A., Mansson, K., Millborg, M., Nilsson, C., Ohlin, A. -M., Olofsson, A., Osberg, A., Pedersen, A., Risbecker, K., Rosenberg, K., Samuelsson, J., Shayesteh, M., Skoglund, K., Stjernberg, M., Thorsen, C., Beer, J. 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S., Pickavance, G., Mcdonnell, J., Williams, A., Gooding, T., Wagner, H., Suryani, S., Singal, A., Sircar, S., Bilas, R., Hutchinson, P., Wakeman, A., Stokes, M., Paul, N., Aziz, M., Ramesh, C., Wilson, P., Franklin, S., Fairhead, S., Thompson, J., St Joseph, V., Taylor, G., Tragen, D., Seamark, D., Paul, C., Richardson, M., Jefferies, A., Sharp, H., Jones, H., Giles, C., Page, M., Oginni, O., Aldegather, J., Wetherwell, S., Lumb, W., Evans, P., Scouller, F., Macey, N., Stipp, Y., West, R., Thurston, S., Wadeson, P., Matthews, J., Pandya, P., Gallagher, A., Railton, T., Sinha, B., Russell, D., Davies, J. A., Ainsworth, P., Jones, C. P., Weeks, P., Eden, J., Kernick, D., Murdoch, W., Lumley, L., Patel, R. P., Wong, S. W., Saigol, M., Ladha, K., Douglas, K., Cumberlidge, D. F., Bradshaw, C., Van Zon, G., Jones, K. P., Thomas, M. J., Watson, E., Sarai, B., Ahmad, N., Willcock, W., Cairns, J., Sathananthan, S., de Kare-Silver, N., Gilliland, A., Strieder, E., Howitt, A., Vishwanathan, B., Bird, N., Gray, D., Clark, M., Bisatt, J., Litchfield, J., Fisher, E., Fooks, T., Kelsall, A. R., Alborough, E., Wakeling, J., Parfitt, M., Milne, K., Rogers, S., Priyadharshan, R., Oliver, J. L., Davies, E., Abushal, S., Jacobs, M., Hutton, C., Walls, N. I., Thompson, R., Chigbo, C., Zaidi, S. M. A., Howard, M., Butter, K. C., Barrow, S., Little, H., Haq, I. U., Gibbons, L., Glencross, S., Mcleod, A. J., Poland, K., Mulholland, C., Warke, A., Conn, P., Burns, G., Smith, R. N., Lowe, S., Kamath, R., Dau, H. S., Webster, J., Hodgins, I., Vercoe, S., Roome, P. C., Pinnock, H., Patel, J. R. A., Ali, A., Hart, N., Davies, R., Stuart, E., Neden, C. A., Danielsen, M., Heath, R., Sharma, P., Galloway, S., Hawkins, C., Oliver, R., Aylward, M., Mannion, S., Braddick, M., Edwards, D., Rothwell, A. 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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P., Hesketh, L., Hoffmann, B., Johnson, K., Juergens, C., Kassam, I., Lawlor, V., Lehman, M., Lehman, S., Leung, D., Mackay, S., Mackenzie, M., Mccarthy, C., Mcintosh, C., Mckeon, L., Morrison, H., Mussap, C., Myers, J. -D., Nagalingam, V., Oldfield, G., O'May, V., Palmer, J., Parsons, L., Patching, K., Patching, T., Paul, V., Plotz, M., Preston, S., Rashad, H., Ratcliffe, M., Raynes, S., Rose, J., Sanders, L., Seremetkoska, M., Setio, H., Shone, S., Shrestha, P., Singh, C., Singleton, C., Stoyanov, N., Sutcliffe, S., Swaraj, K., Tarrant, J., Thompson, S., Tsay, I. M., Vorster, M., Waldman, A., Wallis, L., Wilford, E., Wong, K., Luton, R., Gupta, M., Pandey, A. S., Cheung, S., Leader, R., Beaudry, P., Ayala-Paredes, F., Berlingieri, J., Heath, J., Poirier, G., Du Preez, M., Nadeau, R., Dresser, G., Dhillon, R., Hruczkowski, T., Schweitzer, B., Coutu, B., Angaran, P., Macdonald, P., Vizel, S., Fikry, S., Parkash, R., Lavoie, A., Cha, J., Ramjattan, B., Bonet, J., Ahmad, K., Aro, L., Aves, T., Beaudry, K., Bergeron, C., Bigcanoe, J., Bignell, N., Breakwell, L., Burke, E., Carroll, L., Clarke, B., Cleveland, T., Daheb, S., Dehghani, P., Denis, I., Djaidani, Z., Dorian, P., Douglass, S., Dunnigan, J., Ewert, A., Farquhar, D., Fearon, A., Ferleyko, L., Fournier, D., Fox, B., Grenier, M. -C., Gulliver, W., Haveman, K., Hines, C., Hines, K., Jackson, A. M., Jean, C., Jethoo, G., Kahlon, R., Kelly, S., Kim, R., Korley, V., Kornder, J., Kwan, L., Largy, J., Lewis, C., Lewis, S., Mangat, I., Moor, R., Navratil, J., Neas, I., Otis, J., Otis, R., Pandey, M., Petrie, F., Pinter, A., Raines, M., Roberts, P., Robinson, M., Sas, G., Schulman, S., Snell, L., Spearson, S., Stevenson, J., Trahey, T., Wong, S., Wright, D., El-Aziz, A. A., Seif, S. K. A., El Din, M. G., El Etriby, S., Elbahry, A., El-Etreby, A., Elkhadem, M., Katta, A., Khairy, T., Mowafy, A., Nawar, M., Ohanissian, A., Reda, A., Reda, M., Salem, H., Sami, N., Samir, S., Setiha, M., Sobhy, M., Soliman, A., Taha, N., Tawfik, M., Zaatout, E., Kettles, D., Bayat, J., Siebert, H., Horak, A., Kelfkens, Y., Garda, R., Pillay, T., Guerra, M., van Zyl, L., Theron, H., Murray, A., Louw, R., Greyling, D., Mntla, P., Ueckermann, V., Loghdey, R., Ismail, S., Ahmed, F., Engelbrecht, J., Ramdass, A., Maharajh, S., Oosthuysen, W., Angel, G., Bester, C., Booysen, M., Boshoff, C., Cannon, C., Cassimjee, S., Chami, C., Conway, G., Davids, A., de Meyer, L., Du Plessis, G., Ellis, T., Henley, L., Karsten, M., Loyd, E., Marks, J., Mavhusa, L., Mostert, M., Page, A., Rikhotso, L., Salie, M., Sasto, J., Shaik, F., Skein, A., Smith, L., Tarr, G., Tau, T., van Zyl, F., Yousef, G., Agrawal, A., Nathani, M., Ibrahim, M., Esheiba, E. 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., and Worthy, V.

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

37. Empagliflozin in the treatment of heart failure with reduced ejection fraction in addition to background therapies and therapeutic combinations (EMPEROR-Reduced): a post-hoc analysis of a randomised, double-blind trial

Author

Subodh Verma, Nitish K Dhingra, Javed Butler, Stefan D Anker, Joao Pedro Ferreira, Gerasimos Filippatos, James L Januzzi, Carolyn S P Lam, Naveed Sattar, Barbara Peil, Matias Nordaby, Martina Brueckmann, Stuart J Pocock, Faiez Zannad, Milton Packer, M Packer, S Anker, J Butler, G Filippatos, S Pocock, F Zannad, JP Ferreira, M Brueckmann, J George, W Jamal, FK Welty, M Palmer, T Clayton, KG Parhofer, TR Pedersen, B Greenberg, MA Konstam, KR Lees, P Carson, W Doehner, A Miller, M Haas, S Pehrson, M Komajda, I Anand, J Teerlink, A Rabinstein, T Steiner, H Kamel, G Tsivgoulis, J Lewis, J Freston, N Kaplowitz, J Mann, J Petrie, S Perrone, S Nicholls, S Janssens, E Bocchi, N Giannetti, S Verma, J Zhang, J Spinar, M-F Seronde, M Boehm, B Merkely, V Chopra, M Senni, S Taddi, H Tsutsui, D-J Choi, E Chuquiure, HPB La Rocca, P Ponikowski, JRG Juanatey, I Squire, J Januzzi, I Pina, R Bernstein, A Cheung, J Green, S Kaul, C Lam, G Lip, N Marx, P McCullough, C Mehta, J Rosenstock, N Sattar, B 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Potu, R, Sai-Sudhakar, C, Saltzberg, M, Sauer, A, Shah, P, Skopicki, H, Bui, H, Carr, K, Stevens, G, Tahirkheli, N, Tallaj, J, Yousuf, K, Trichon, B, Welker, J, Tolerico, P, Vest, A, Vivo, R, Wang, X, Abadier, R, Dunlap, S, Weintraub, N, Malik, A, Kotha, P, Zaha, V, Kim, G, Uriel, N, Greene, T, Salacata, A, Arora, R, Gazmuri, R, Kobayashi, J, Iteld, B, Vijayakrishnan, R, Dab, R, Mirza, Z, Marques, V, Nallasivan, M, Bensimhon, D, Peart, B, Saint-Jacques, H, Barringhaus, K, Contreras, J, Gupta, A, Koneru, S, Nguyen, V, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
Male, medicine.medical_specialty, Angiotensin receptor, Glucoside, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Adrenergic beta-Antagonists, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Placebo, 03 medical and health sciences, Angiotensin Receptor Antagonists, 0302 clinical medicine, Endocrinology, Mineralocorticoid receptor, Glucosides, Double-Blind Method, Internal medicine, Post-hoc analysis, Internal Medicine, medicine, Empagliflozin, Humans, 030212 general & internal medicine, Benzhydryl Compounds, ComputingMilieux_MISCELLANEOUS, Aged, Benzhydryl Compound, Heart Failure, Ejection fraction, business.industry, Angiotensin Receptor Antagonist, Adrenergic beta-Antagonist, Angiotensin-Converting Enzyme Inhibitor, Stroke Volume, medicine.disease, 3. Good health, Heart failure, ACE inhibitor, Female, Hypotension, business, medicine.drug, Human
Abstract

Contains fulltext : 249977.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as β blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; p(interaction)=0·18). A similar result was seen for β blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; p(interaction)=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus β blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; p(interaction)=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.

Published
2022

38. Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry

Author

Jitendra PS. Sawhney, Veerappa A. Kothiwale, Vikas Bisne, Rajashekhar Durgaprasad, Praveen Jadhav, Manoj Chopda, Velam Vanajakshamma, Ramdhan Meena, Govindan Vijayaraghavan, Kamaldeep Chawla, Jagan Allu, Karen S. Pieper, A. John Camm, Ajay K. Kakkar, Jean-Pierre Bassand, David A. Fitzmaurice, Samuel Z. Goldhaber, Shinya Goto, Sylvia Haas, Werner Hacke, Lorenzo G. Mantovani, Frank Misselwitz, Alexander G.G. Turpie, Martin van Eickels, Freek W.A. Verheugt, Gloria Kayani, Keith A.A. Fox, Bernard J. Gersh, Hector Lucas Luciardi, Harry Gibbs, Marianne Brodmann, Frank Cools, Antonio Carlos Pereira Barretto, Stuart J. Connolly, Alex Spyropoulos, John Eikelboom, Ramon Corbalan, Dayi Hu, Petr Jansky, Jørn Dalsgaard Nielsen, Hany Ragy, Pekka Raatikainen, Jean-Yves Le Heuzey, Harald Darius, Matyas Keltai, Sanjay Kakkar, Jitendra Pal Singh Sawhney, Giancarlo Agnelli, Giuseppe Ambrosio, Yukihiro Koretsune, Carlos Jerjes Sánchez Díaz, Hugo Ten Cate, Dan Atar, Janina Stepinska, Elizaveta Panchenko, Toon Wei Lim, Barry Jacobson, Seil Oh, Xavier Viñolas, Marten Rosenqvist, Jan Steffel, Pantep Angchaisuksiri, Ali Oto, Alex Parkhomenko, Wael Al Mahmeed, David Fitzmaurice, D.Y. Hu, K.N. Chen, Y.S. Zhao, H.Q. Zhang, J.Z. Chen, S.P. Cao, D.W. Wang, Y.J. Yang, W.H. Li, Y.H. Yin, G.Z. Tao, P. Yang, Y.M. Chen, S.H. He, Ying Wang, Yong Wang, G.S. Fu, X. Li, T.G. Wu, X.S. Cheng, X.W. Yan, R.P. Zhao, M.S. Chen, L.G. Xiong, P. Chen, Y. Jiao, Y. Guo, L. Xue, F.Z. Wang, H. Li, Z.M. Yang, C.L. Bai, J. Chen, J.Y. Chen, X. Chen, S. Feng, Q.H. Fu, X.J. Gao, W.N. Guo, R.H. He, X.A. He, X.S. Hu, X.F. Huang, B. Li, J. Li, L. Li, Y.H. Li, T.T. Liu, W.L. Liu, Y.Y. Liu, Z.C. Lu, X.L. Luo, T.Y. Ma, J.Q. Peng, X. Sheng, X.J. Shi, Y.H. Sun, G. Tian, K. Wang, L. Wang, R.N. Wu, Q. Xie, R.Y. Xu, J.S. Yang, L.L. Yang, Q. Yang, Y. Ye, H.Y. Yu, J.H. Yu, T. Yu, H. Zhai, Q. Zhan, G.S. Zhang, Q. Zhang, R. Zhang, Y. Zhang, W.Y. Zheng, B. Zhou, Z.H. Zhou, X.Y. Zhu, S. Kakkar, J.P.S. Sawhney, P. Jadhav, R. Durgaprasad, A.G. Ravi Shankar, R.K. Rajput, K. Bhargava, R. Sarma, A. Srinivas, D. Roy, U.M. Nagamalesh, M. Chopda, R. Kishore, G. Kulkarni, P. Chandwani, R.A. Pothiwala, M. Padinhare Purayil, S. Shah, K. Chawla, V.A. Kothiwale, B. Raghuraman, G. Vijayaraghavan, V.M. Vijan, G. Bantwal, V. Bisne, A. Khan, J.B. Gupta, S. Kumar, D. Jain, S. Abraham, D. Adak, A. Barai, H. Begum, P. Bhattacharjee, M. Dargude, D. Davies, B. Deshpande, P. Dhakrao, V. Dhyani, S. Duhan, M. Earath, A. Ganatra, S. Giradkar, V. Jain, R. Karthikeyan, L. Kasala, S. Kaur, S. Krishnappa, A. Lawande, B. Lokesh, N. Madarkar, R. Meena, P. More, D. Naik, K. Prashanth, M. Rao, N.M. Rao, N. Sadhu, D. Shah, M. Sharma, P. Shiva, S. Singhal, S. Suresh, V. Vanajakshamma, S.G. Panse, Y. Koretsune, S. Kanamori, K. Yamamoto, K. Kumagai, Y. Katsuda, K. Sadamatsu, F. Toyota, Y. Mizuno, I. Misumi, H. Noguchi, S. Ando, T. Suetsugu, M. Minamoto, Hiroshi Oda, K. Shiraishi, S. Adachi, K. Chiba, H. Norita, M. Tsuruta, T. Koyanagi, H. Ando, T. Higashi, K. Okada, S. Azakami, S. Komaki, K. Kumeda, T. Murayama, J. Matsumura, Y. Oba, R. Sonoda, K. Goto, K. Minoda, Y. Haraguchi, H. Suefuji, H. Miyagi, H. Kato, Tadashi Nakamura, Tsugihiro Nakamura, H. Nandate, R. Zaitsu, Yoshihisa Fujiura, A. Yoshimura, H. Numata, J. Ogawa, H. Tatematsu, Y. Kamogawa, K. Murakami, Y. Wakasa, M. Yamasawa, H. Maekawa, S. Abe, H. Kihara, S. Tsunoda, Katsumi Saito, Kazuyuki Saito, T. Fudo, K. Obunai, H. Tachibana, I. Oba, T. Kuwahata, S. Higa, M. Gushiken, T. Eto, H. Yoshida, D. Ikeda, Yoshitake Fujiura, M. Ishizawa, M. Nakatsuka, K. Murata, C. Ogurusu, M. Shimoyama, M. Akutsu, I. Takamura, F. Hoshino, N. Yokota, T. Iwao, K. Tsuchida, M. Takeuchi, Y. Hatori, Y. Kitami, Yoichi Nakamura, R. Oyama, M. Ageta, Hiroyuki Oda, Y. Go, K. Mishima, T. Unoki, S. Morii, Yuhei Shiga, H. Sumi, T. Nagatomo, K. Sanno, K. Fujisawa, Y. Atsuchi, T. Nagoshi, T. Seto, T. Tabuchi, M. Kameko, K. Nii, K. Oshiro, H. Takezawa, S. Nagano, N. Miyamoto, M. Iwaki, Yuichiro Nakamura, M. Fujii, M. Okawa, Masahiko Abe, Masatake Abe, Mitsunori Abe, T. Saito, T. Mito, K. Nagao, J. Minami, T. Mita, I. Sakuma, T. Taguchi, S. Marusaki, H. Doi, M. Tanaka, T. Fujito, M. Matsuta, T. Kusumoto, S. Kakinoki, K. Ashida, N. Yoshizawa, J. Agata, O. Arasaki, M. Manita, M. Ikemura, S. Fukuoka, H. Murakami, S. Matsukawa, Y. Hata, T. Taniguchi, T. Ko, H. Kubo, M. Imamaki, M. Akiyama, M. Inagaki, H. Odakura, T. Ueda, Y. Katsube, A. Nakata, H. Watanabe, M. Techigawara, M. Igarashi, K. Taga, T. Kimura, S. Tomimoto, M. Shibuya, M. Nakano, K. Ito, T. Seo, S. Hiramitsu, H. Hosokawa, M. Hoshiai, M. Hibino, K. Miyagawa, Hajime Horie, N. Sugishita, Yukio Shiga, A. Soma, K. Neya, Tetsuro Yoshida, Tomoki Yoshida, M. Mizuguchi, M. Ishiguro, T. Minagawa, M. Wada, H. Mukawa, F. Okuda, S. Nagasaka, Y. Abe, Sen Adachi, Susumu Adachi, T. Adachi, K. Akahane, T. Amano, K. Aoki, T. Aoyama, H. Arai, S. Arima, T. Arino, H. Asano, T. Asano, J. Azuma, T. Baba, T. Betsuyaku, H. Chibana, H. Date, J. Doiuchi, Y. Emura, M. Endo, Y. Fujii, R. Fujiki, A. Fujisawa, Y. Fujisawa, T. Fukuda, T. Fukui, N. Furukawa, T. Furukawa, W. Furumoto, T. Goto, M. Hamaoka, N. Hanazono, K. Hasegawa, T. Hatsuno, Y. Hayashi, K. Higuchi, K. Hirasawa, H. Hirayama, M. Hirose, S. Hirota, M. Honda, Hideki Horie, T. Ido, O. Iiji, H. Ikeda, K. Ikeda, K. Ikeoka, M. Imaizumi, H. Inaba, T. Inoue, F. Iseki, A. Ishihara, N. Ishioka, N. Ito, T. Iwase, H. Kakuda, J. Kamata, H. Kanai, H. Kanda, M. Kaneko, H. Kano, T. Kasai, T. Kato, Y. Kato, Y. Kawada, K. Kawai, K. Kawakami, S. Kawakami, T. Kawamoto, S. Kawano, J. Kim, T. Kira, H. Kitazawa, H. Kitazumi, T. Kito, T. Kobayashi, T. Koeda, J. Kojima, H. Komatsu, I. Komatsu, Y. Koshibu, T. Kotani, T. Kozuka, Y. Kumai, T. Kumazaki, I. Maeda, K. Maeda, Y. Maruyama, S. Matsui, K. Matsushita, Y. Matsuura, K. Mineoi, H. Mitsuhashi, N. Miura, S. Miyaguchi, S. Miyajima, H. Miyamoto, A. Miyashita, S. Miyata, I. Mizuguchi, A. Mizuno, T. Mori, O. Moriai, K. Morishita, O. Murai, Sho Nagai, Shunichi Nagai, E. Nagata, H. Nagata, A. Nakagomi, S. Nakahara, M. Nakamura, R. Nakamura, N. Nakanishi, T. Nakayama, R. Nakazato, T. Nanke, J. Nariyama, Y. Niijima, H. Niinuma, Y. Nishida, Y. Nishihata, K. Nishino, H. Nishioka, K. Nishizawa, I. Niwa, K. Nomura, S. Nomura, M. Nozoe, T. Ogawa, N. Ohara, M. Okada, K. Okamoto, H. Okita, M. Okuyama, H. Ono, T. Ono, Y. Onuki Pearce, S. Oriso, A. Ota, E. Otaki, Y. Saito, H. Sakai, N. Sakamoto, Y. Sakamoto, Y. Samejima, Y. Sasagawa, H. Sasaguri, A. Sasaki, T. Sasaki, Kazuki Sato, Kiyoharu Sato, M. Sawano, S. Seki, Y. Sekine, Y. Seta, K. Sezaki, N. Shibata, Y. Shiina, H. Shimono, Y. Shimoyama, T. Shindo, H. Shinohara, R. Shinohe, T. Shinozuka, T. Shirai, T. Shiraiwa, Y. Shozawa, T. Suga, C. Sugimoto, Kazuo Suzuki, Keita Suzuki, Shu Suzuki, Shunji Suzuki, Susumu Suzuki, Y. Suzuki, M. Tada, A. Taguchi, T. Takagi, Y. Takagi, K. Takahashi, S. Takahashi, H. Takai, C. Takanaka, S. Take, H. Takeda, K. Takei, K. Takenaka, T. Tana, G. Tanabe, K. Taya, H. Teragawa, S. Tohyo, S. Toru, Y. Tsuchiya, T. Tsuji, K. Tsuzaki, H. Uchiyama, O. Ueda, Y. Ueyama, N. Wakaki, T. Wakiyama, T. Washizuka, M. Watanabe, T. Yamada, T. Yamagishi, H. Yamaguchi, Kenichi Yamamoto, Kentaro Yamamoto, Kunihiko Yamamoto, T. Yamamoto, M. Yamaura, M. Yamazoe, K. Yasui, Y. Yokoyama, K. Yoshida, T.W. Lim, C.K. Ching, C.G. Foo, J.H. Chow, D.D. Chen, F.R. Jaufeerally, Y.M. Lee, G. Lim, W.T. Lim, S. Thng, S.Y. Yap, C. Yeo, S. Oh, H.N. Pak, J.-B. Kim, J.H. Kim, S.-W. Jang, D.H. Kim, D.R. Ryu, S.W. Park, D.-K. Kim, D.J. Choi, Y.S. Oh, M.-C. Cho, S.-H. Kim, H.-K. Jeon, D.-G. 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Y., Angchaisuksiri, P., 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., Oto, A., Altun, A., Ozdogru, I., Ozdemir, K., Yilmaz, O., Aydinlar, A., Yilmaz, M. 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A., Bergesio, L., Berli, F., Berli, M., Borchowiec, S., Buzzetti, C., Cabrini, R., Campisi, V., Cappi, A. L., Carrizo, R., Colombo Berra, F., Costabel, J. P., Costamagna, O. J. A., Damonte, A. A., De Urquiza, I. N., Diez, F., Edén, M. F., Fanuele, M., Fernandez Voena, F., Foa Torres, M., Funosas, C., Giacomi, M. P., Gimenez, C. H., Gurfinkel, E. P., de L. M. Had, 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., Perez Prados, G., Pontoriero, J., Potito, R. N., Ricotti, C., Rodriguez, M. A., Rolandi, F., Said Palladino, M. E., 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., Barretto, A. C. P., Sobral Filho, D. C., Jaber, J., Armaganijan, D., Faria Neto, J., Steffens, A., Kunz Sebba Barroso de Souza, W., de Souza Neto, J. D., Ribeiro, J. M., Silveira Teixeira, M., Ferreira Rossi, P. R., Pires, L., Moreira, D., Moura Jorge, J. C., Menezes Lorga Filho, A., Bodanese, L. C., Westerlund Montera, M., Del Carlo, C. H., Da Rocha Rodrigues, T., Alves da Costa, F. A., Lopes, A., Lopes, R., Araújo, G. R., Fernandes Manenti, E. R., Kerr Saraiva, J. F., Ferreira Braga, J. C., Negri, A., Souto, L., Moncada, C., Bertolim Precoma, D., Roquette, F., Reis, G., Ramos Filho, R. A., Lanna Figueiredo, E., Vieira Botelho, R., Munhoz da Fontoura Tavares, C., Costantini Frack, C. R., Abdalla Saad, J., Finimundi, H. C., Pisani, C., Chemello, D., Pereira Martins, M., Broilo França, C. C., Alban, F., Aranha Rosito, G. B., de Moura Xavier Moraes Junior, J. B., Tumelero, R. T., Nigro Maia, L., Simões de Almeida, R., do Carmo Borges, N. C., Gomes Ferreira, L. G., Agliardi, P., Alves de Oliveira Gomes, J., Araujo, V., Arruda Nakazone, M., Barbosa, T., Barroso, S., Belisario Falchetto, E., Bellotti Lopes, H., Benez Teixeira Lemos, M. A., Biazus, G., Borges Queiroz, L., Camazzola, F. E., Caporale, M., Cardoso Boscato, S., Chieza, F., Chokr, M. O., Clemente Mingireanov, R., Codonho Góes, N., Correa, C., Costa, M., Costantini Ortiz, C., da Silva, L. S., da Silva Paulitsch, F., da Silveira, J. A., Daros, E., de Araújo, G. R., Del Monaco, M. I., Dias, C., Dias, M. A., Drummond Wainstein, A. P., Ely Pizzato, P., Esteves, D. C., Fabri, P., Félix Lorenzato Fonseca, T., Fernandes, E., Fonseca, C., Frack Costantini, C. R., Franchin Ferraz, R., Freire, F., Gottardo, P., Guanaes, D., Guizzardi, S., Hettwer Magedanz, E., Igansi, F., Jannuzzi, F., Junior, G., Komar, D., Lino, E. G., Lopes, D., Lourenço da Silva Júnior, O., Lustosa, E., Macagnan, A. P., Marinho, M. C., Mazzoni, M., Melo, G., Mortari, L., Mouco, O. M. C. C., Nanzer Vital, C., Ormundo, C., Oss Emmer, S., Palmegiani, E., Pavani, R., Pereira, L., Pereira, V. L., Perreira, R., Poletti, S., Quaia Fortunato, S. C., Queirantes, C., Ramos Pereira, N., Rech, R. L., Ribeiro, S., Rodrigues, A., Roesch, H., Ruaro Reichert, T., Santos, D., Santos, I., Santos, M., Seroqui, M. V., Silva, S., Soares, L., Spolaor, L., Stoll, C., Toazza Duda, N., Trama, L., Unterkircher, B., Valois, M. V., Vargas, T., Viana, T., Vicente, C., Vidal Armaganijan, L., Vieira Homem, R., Vieira Torres, L. G., Vila Boas, L., Villaça Guimarães Filho, F., Corbalan, R., Eggers, G., Bugueño Gutiérrez, C., Arriagada, G., Potthoff Cardenas, S., Stockins Fernandez, B. A. J., Conejeros, C., Houzvic, C., Marin Cuevas, P., Montecinos, H., Forero, A., Lanas, F., Larico Gómez, M., Charme Vilches, G., Rey, C., Astudillo, C., Aguilar, J., Campisto, Y., Lara, C., Molina, E., Munoz Oyarzon, J., Olguin, V., Vergara, M., Villan, C., Sánchez Díaz, C. J., Illescas Diaz, J., Leal Cantú, R., Ramos Zavala, M. G., Cabrera Jardines, R., Espinola Zavaleta, N., Villarreal Umaña, S., López Rosas, E., Llamas Esperón, G., Pozas, G., Cardona Muñoz, E., Matadamas Hernández, N., Leyva Rendón, A., García Hernández, N., de los Ríos Ibarra, M., Virgen Carrillo, L., López Villezca, D., Hernández Herrera, C., López Prieto, J. J., Gaona Rodríguez, R., Villeda Espinosa, E., Flores Martínez, D., Velasco Barcena, J., Yong, R., Rodríguez Briones, I., Leiva Pons, J. L., Álvarez López, H., Olvera Ruiz, R., Díaz de la Vega, C., Cantú Brito, C., Chuquiure Valenzuela, E., Reyes-Sanchez, R., Bazzoni Ruiz, A., Nandayapa Flores, O., Benavides Gonzalez, M., Arriaga Nava, R., Morales Cerda, J. D., Fierro Fierro, O., Fajardo Campos, P., Alfaro, T. A. A., Altamirano Bellorin, S., Avena, R., Chavarria, M., Espinosa, I., Flores Silva, F., Garcia Nava, R. H., Godoy, K., Gonzalez Felix, E. J., Gonzalez Garcia, C. L., Gonzalez Salas, L. G., Guajardo, P., Hernandez Gonzalez, S., Izquierdo, T., Mancilla Ortiz, M. C., Martinez Vasquez, D., Mendoza, N., Morales, J., Nikitina, N., Ochoa Aybar, S., Ortiz, A., Padilla Macias, P., Perez, F., Perez Sanchez, J. A., Piña Toledano, S., Ramos Gonzalez, M., Rivera Ramos, C., Roa Castro, V., Romero Cardona, G., Ruiz Cornejo, M., Salinas, A., Santana, G., Sida Perez, P., Tovar Castaneda, A. C., Trujillo Cortes, R., Brodmann, M., 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., Stöcklöcker, C., Vogel, B., Vonbank, A., Wöhrer, C., Zanolin, D., Cools, F., Paparella, G., Vandergoten, P., Parqué, 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., Anné, W., Vercammen, J., Purnode, P., Blankoff, I., Faes, D., Balthazar, Y., Beutels, M., Maréchal, 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., Conde Y Bolado, A., 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., Jansky, P., 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., Majerníkova, M., Michalik, D., Potuznik, P., Prochazkova, E., Sulc, A., Sveceny, J., Valtova, M., Zidek, M., Zika, J., Nielsen, 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., Domínguez, 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., Raatikainen, P., Airaksinen, J., Arola, O., Koistinen, J., Nappila, H., Peltomäki, K., Rasanen, V., Vasankari, T., Le Heuzey, J. -Y., 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. P., Fedorowsky, A., Casassus, F., Berneau, J. -B., Chemin, F., Falvo, N., Perron, J. -M., Poulard, J. -E., Barreau, A., Beltra, C., Corrihons, E., Decarsin, N., Dubois, B., Ducasse, E., Giry, X., Kemmel, A., Ledure, S., Lemaire, N., Robin, F., Rosolin, N., Sanchez, D., Suissa, A., Darius, H., Königer, G., Purr, J., Gerbaulet, U., Kellner, B. -T., Kopf, A., Schäfer, T., Zauzig, H., Riegel, P., Hohensee, H., Eißfeller, E., Eder, W., Rehling, G., Glatzel, D., Zutz, S., Heinz, G. -U., Menke, H., Pustelnik, A., Sandow, P., Ludwig, N., Wiswedel, H., Wildenauer, W., Axthelm, C., Schwarz, T., Babyesiza, A., Stuchlik, G., Zimny, H. -H., Kropp, M., Kahl, F., Caspar, A., Omankowsky, S., Läßig, T., Hartmann, H. -J., Lehmann, G., Bindig, H. -W., Hergdt, G., Reimer, D., Hauk, J., Dorsch, W., Dshabrailov, J., Michel, H., Rapp, K. -A., Vormann, R., Mayer, P., Horstmeier, U., Eissing, V., Hey, H., Leuchtgens, H., Lilienweiß, V., Kolitsch, K., Schubert, C., Lauer, H., Buchner, T., Brauer, G., Kamin, S., Müller, K., Abdel-Qader, M., Baumbach, S., Ebert, H. -H., Schwencke, C., Schellong, S., Bernhardt, P., Karolyi, L., Sievers, B., Haverkamp, W., Salbach, P., Röhnisch, J. -U., Schoen, S., Erdle, W., Mueller, T., Mueller, H., Mitrovic, V., Babjakova, Z., Bergner, K., Boehme, S., Bonin, K., Buckert, D., Busch, F., Dichristin, U., Diez, S., Fleck, A., Flint, K., Floegel, H., Fritz, C., Frommhold, R., Gehre, J., Geyer, J., Grytzmann, A., Hahn, M., Helgert, K., Hubert, K., Kirchner-Volker, K., Klein, V., Kroll, D., Krueger, A., Lehmann, R., Mann, L., Maselli, A., Menken, G., Mikes, K., Mortan, H., Nasser, N., Nicolaus, D., Plauskat, A., Pomper, L., Quietzsch, A., Ravenhorst, C., Reichelt, C., Reimer, C., Schaefer, B., Scharrer, S., Schirmer, K., Schmidt, K., Schoene, R., Schulze, J., Schuppe, M., Simon, S., Sommer, S., Spranger, K., Talkenberger, A., Tauber, K., Tetlak, A., Toennishoff, T., Voelkel-Babyesiza, R., Voigts, B., Weiser, U., Wesendorf, S., Wildenauer, S., Wolf, T., Wurziger, J., Zak, J., Zauzig, H. -D., Ziefle, S., Zincke, S., Keltai, M., Vangel, S., Szalai, G., Merkely, B., Kancz, S., Boda, Z., Nagy, A., Laszlo, Z., Matoltsy, A., Gaszner, B., Polgar, P., Habon, T., Noori, E., Juhasz, G., Kanakaridisz, N., Szentpeteri, I., Juhasz, F., Vertes, A., Papp, A., May, Z., Ferenczi, J., Egyutt, M., Kis, E., Engelthaler, G., Szantai, G., Fulop, E., Gombos, P., Gulyas, D., Jen, P., Kiralyhazine Gyorke, E., Kovacs, M., Kovacsne Levang, S., Marianna, S., Radics, Z., Sydó, N., Szalo, R., Szilagyi, A., Sztanyik, F., Vandrus, B., Agnelli, G., Ambrosio, G., Tiraferri, E., Santoro, R., Testa, S., Di Minno, G., Moia, M., Caimi, T. M., Martini, G., Tessitori, M., Cappelli, R., Poli, D., Quintavalla, R., Melone, F., Cosmi, F., Pizzini, A., Piseddu, G., Fanelli, R., Latella, C., Santi, R., Pancaldi, L., De Cristofaro, R., Palareti, G., De Blasio, A., Salerno Uriarte, J., Minetti, F., Pogliani, E. M., Lonati, L. M., Accogli, M., Ciampani, N., Malengo, S., Feola, M., Raisaro, A., Fattore, L., Grilli, P., Germini, F., Settimi, M., Alunni, M., Duranti, G., Tedeschi, L., Baglioni, G., Avanzino, G., Berardi, M., Pannacci, V., Giombolini, A., Nicoli, S., Scarponi, T., Allasia, B., Ricciarini, P., Nasorri, R., Argena, A., Bossolasco, P., Ronchini, P., Filippi, A., Tradati, F., Bulla, C., Donzelli, L., Foppa, L., Bottarelli, M. L., Tomasello, A., Mauric, A., Femiano, C., Reggio, R., Lillo, F., Mariani, A., Forcignanò, F., Volpe, M., D'Avino, M., Bongiorni, M. G., Severi, S., Capucci, A., Lodigiani, C., Salomone, E., Serviddio, G., Tondo, C., Golino, P., Mazzone, C., Iacopino, S., Pengo, V., Galvani, M., Moretti, L., Ambrosino, P., Banfi, E., Biagioli, V., Bianchi, A., Boggian, G., Breschi, M., Brusorio, S., Calcagnoli, F., Campagna, G., Carpenedo, M., Ciabatta, C., Ciliberti, G., Cimmino, G., D'Arienzo, C., Di Gennaro, L., Fedele, M., Ferrini, P. M., Granzow, K., Guazzaloca, G., Guerra, F., Lo Buglio, A., Longo, S., Macellari, F., Mesolella, E., Mollica Poeta, E., Occhilupo, P., Oriana, V., Rangel, G., Salomone, L., Scaccianoce, A., Scarone, C., Segreti, L., Sottilota, G., Villani, R., Zecca, C., ten Cate, H., Ruiter, J. H., Klomps, H., Bongaerts, M., Pieterse, M. G. C., Guldener, C., Herrman, J. -P., Lochorn, G., Lucassen, A., Adriaansen, H., The, S. H. K., Nierop, P. R., Hoogslag, P. A. M., Hermans, W., Groenemeijer, B. E., Terpstra, W., Buiks, C., Boersma, L. V. 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Subjects
Registrie, Male, Time Factors, Anticoagulant therapy, Arrhythmia, Atrial fibrillation, GARFIELD-AF, 030204 cardiovascular system & hematology, Electrocardiography, 0302 clinical medicine, Risk Factors, Anticoagulant therapy, Arrhythmia, Atrial fibrillation, GARFIELD-AF, Aged, Atrial Fibrillation, Female, Follow-Up Studies, Humans, Incidence, India, Prevalence, Prognosis, Prospective Studies, Survival Rate, Thromboembolism, Registries, Risk Assessment, Medicine, 030212 general & internal medicine, Prospective cohort study, Incidence (epidemiology), cardiovascular system, medicine.symptom, Cardiology and Cardiovascular Medicine, Risk assessment, Human, medicine.medical_specialty, Time Factor, RD1-811, Prognosi, Follow-Up Studie, 03 medical and health sciences, Internal medicine, Diseases of the circulatory (Cardiovascular) system, cardiovascular diseases, Risk factor, Survival rate, Fibrillation, business.industry, Risk Factor, ta3121, medicine.disease, Clinical trial, Prospective Studie, RC666-701, Surgery, Clinical and Preventive Cardiology, business
Abstract

Background: The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. Methods and results: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012–2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P

Published
2018

39. Management of postoperative pancreatic fistula after pancreatoduodenectomy: Analysis of 600 cases of pancreatoduodenectomy patients over a 10-year period at a single institution

Author

Yusuke Watanabe, Yasuhisa Mori, Naoki Ikenaga, Takao Ohtsuka, Yoshihiro Miyasaka, Noboru Ideno, Masafumi Nakamura, and Kohei Nakata

Subjects
Adult, Male, Reoperation, medicine.medical_specialty, Percutaneous, Postoperative Hemorrhage, 030230 surgery, Pancreaticoduodenectomy, Pancreatic Fistula, Young Adult, 03 medical and health sciences, Pseudoaneurysm, 0302 clinical medicine, medicine, Humans, Local anesthesia, Hospital Mortality, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Mortality rate, Retrospective cohort study, Surgical wound, Middle Aged, medicine.disease, Surgery, Pancreatic fistula, 030220 oncology & carcinogenesis, Drainage, Female, business, Complication
Abstract

Background Although postoperative pancreatic fistula (POPF) is a common and critical complication of pancreatoduodenectomy (PD), effective strategies to prevent POPF have not yet been completely developed. Because appropriate management of POPF is important to reduce the mortality rate after PD, in this study we aimed to evaluate our approach for the management of POPF after PD, including the postoperative course. Methods This retrospective study included 605 consecutive patients who underwent PD at our hospital between 2010 and 2020. All patients who developed POPF were first managed conservatively, with drainage tubes placed during surgery retained to manage POPF. In cases wherein conservative treatment was unsuccessful, open drainage, followed by continuous negative pressure and continuous irrigation, was used. For open drainage, the surgical wound was opened bluntly (approximate length, 5 cm) under local anesthesia, and the fluid was directly and completely drained. Results The prevalence of POPF of grades B and C was 15.4% (n = 93) and 0.33% (n = 2), respectively. Of these patients, 1 required reoperation, 43 recovered with conservative management only, 47 required open drainage, and 4 required image-guided percutaneous drainage. Postoperative hemorrhage with a pseudoaneurysm was identified in 3 (0.66%) patients. The postoperative in-hospital mortality rate was low (n = 1, 0.16%). The rate of successful POPF management was 98.9%. Conclusion Based on our high success rate in POPF management, we consider open drainage to be a safe primary management method for POPF.

Published
2021

40. Gemella haemolysans inhibits the growth of the periodontal pathogen Porphyromonas gingivalis

Author

Nobuo Yoshinari, Tomohiro Miyoshi, Akihiro Yoshida, Reiko Kousaka, Shogo Oge, Satoshi Nakata, Yuki Miura, Hidehiko Ukita, and Yuji Ueno

Subjects
0301 basic medicine, Adult, Male, Saliva, Science, 030106 microbiology, Hemolysis, Article, Microbiology, Periodontal pathogen, 03 medical and health sciences, chemistry.chemical_compound, Antibiosis, Gemella, Medicine, Humans, Symbiosis, Clinical microbiology, Pathogen, Porphyromonas gingivalis, Periodontal Diseases, Aged, Periodontitis, Mouth, Multidisciplinary, biology, business.industry, Middle Aged, biology.organism_classification, medicine.disease, Bacterial Typing Techniques, stomatognathic diseases, 030104 developmental biology, chemistry, Case-Control Studies, Female, Oral Microbiome, Growth inhibition, business, Bacteria
Abstract

The oral microbiome plays an important role in the human microbial community and in maintaining the health of an individual. Imbalances in the oral microbiome may contribute to oral and systemic diseases. The progression of periodontal disease is closely related to the growth of bacteria, such as Porphyromonas gingivalis, in the oral cavity. However, the pathogen growth mechanism specific to periodontal disease remains unknown. This study aimed to identify bacteria associated with periodontal health by focusing on hemolytic bacteria. Unstimulated saliva samples were collected from ten periodontitis patients and five healthy subjects to detect and identify the presence of hemolytic bacteria. The saliva of healthy subjects contained a higher proportion of G. haemolysans than saliva samples from patients with periodontitis. Growth inhibition assays indicated that the protein components contained in the culture supernatant of G. haemolysans directly suppressed the growth of P. gingivalis. This study shows that the presence of G. haemolysans in saliva is associated with periodontal health and that it inhibits the growth of P. gingivalis in vitro.

Published
2021

41. Dose-Dependent Early Postoperative Opioid Use Is Associated with Periprosthetic Joint Infection and Other Complications in Primary TJA

Author

Brian C Chung, Alexander B. Christ, Daniel A. Oakes, Haley Nakata, Nathanael Heckmann, Cory K Mayfield, Gabriel Bouz, and Jay R. Lieberman

Subjects
Male, medicine.medical_specialty, Prosthesis-Related Infections, Arthroplasty, Replacement, Hip, Periprosthetic, Patient Readmission, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Surgical Wound Dehiscence, medicine, Humans, Surgical Wound Infection, Orthopedics and Sports Medicine, Arthroplasty, Replacement, Knee, Aged, Retrospective Studies, Arthritis, Infectious, Pain, Postoperative, 030222 orthopedics, Dose-Response Relationship, Drug, Wound dehiscence, business.industry, Confounding, Venous Thromboembolism, General Medicine, Odds ratio, Perioperative, Middle Aged, medicine.disease, Confidence interval, Pulmonary embolism, Venous thrombosis, Elective Surgical Procedures, Female, Surgery, business, 030217 neurology & neurosurgery
Abstract

Background Opioids are commonly prescribed for postoperative pain following total joint arthroplasty. Despite widespread use, few studies have examined the dose-dependent effect of perioperative opioid use on postoperative complications following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Therefore, we examined the dose-dependent relationship between opioid use and postoperative complications following primary THA and TKA. Methods We queried the Premier Healthcare Database to identify adult patients who underwent primary elective THA or TKA from 2004 to 2014, and quantified opioid consumption within the first 3 postoperative days. Opioid consumption was standardized to morphine milligram equivalents (MMEs). Patients were divided into quintiles on the basis of MME exposure: 172 MMEs. Primary outcomes included postoperative periprosthetic joint infection, pulmonary embolism, deep venous thrombosis, and pulmonary complications. Secondary outcomes included wound infection, wound dehiscence, and readmission within 30 and 90 days postoperatively. Univariate and multivariate analyses were performed to compare differences between groups and to account for confounders. Results A total of 1,525,985 patients were identified. The mean age was 65.7 ± 10.8 years, 598,320 patients (39.2%) were male, and 1,174,314 patients (77.0%) were Caucasian. On multiple logistic regression analysis, increasing MME exposure was associated with a dose-dependent increased risk of postoperative complications. Compared with patients receiving 172 MMEs was associated with greater odds of periprosthetic joint infection (adjusted odds ratio [aOR], 1.37; 95% confidence interval [CI], 1.33 to 1.42), deep venous thromboembolism (aOR, 1.34; 95% CI, 1.30 to 1.38), pulmonary embolism (aOR, 1.29; 95% CI, 1.25 to 1.34), and pulmonary complications (aOR, 1.06; 95% CI, 1.05 to 1.08). Exposure to >172 MMEs was associated with increased risk of wound infection (aOR, 1.37; 95% CI, 1.33 to 1.41), wound dehiscence (aOR, 1.24; 95% CI, 1.19 to 1.31), and readmission within 30 (aOR, 1.21; 95% CI, 1.20 to 1.22) and 90 days (aOR, 1.20; 95% CI, 1.19 to 1.21). Conclusions Increasing opioid use within the early postoperative period following THA or TKA was associated with a dose-dependent increased risk of periprosthetic joint infection and venous thromboembolic events. Level of evidence Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Published
2021

42. Three‐year survival from diagnosis in surgically treated patients in designated and nondesignated cancer care hospitals in Japan

Author

Satomi Odani, Takahiro Tabuchi, Shihoko Koyama, Toshitaka Morishima, Kayo Nakata, Isao Miyashiro, and Sumiyo Okawa

Subjects
survival rate, Adult, Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Adolescent, Cancer Care Facilities, Young Adult, 03 medical and health sciences, quality of health‐care, 0302 clinical medicine, Japan, Neoplasms, Internal medicine, medicine, Humans, Registries, Survival rate, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Hazard ratio, Epidemiology and Prevention, Cancer, Patient survival, Original Articles, General Medicine, Middle Aged, Surgical procedures, medicine.disease, Survival Analysis, Confidence interval, cancer care facility, surgical procedure, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Original Article, Female, business
Abstract

The Japanese national and prefectural governments have accredited high‐capacity, high‐experience cancer care hospitals as “designated cancer care hospitals” to standardize cancer care, centralize patients, and improve clinical outcomes, but the performance of these designated hospitals has not been evaluated. We retrospectively compared 3‐year patient survival in national, prefectural, and nondesignated cancer care hospitals in 2010‐2012 in Osaka using registry‐based data of 86 456 surgically treated cancer patients aged 15 years or older. Hazard ratios and 3‐year survival probabilities were compared among national, prefectural, and nondesignated hospitals using a Cox proportional hazard regression model. Subgroup analyses for six cancers (stomach, colorectum, lung, breast, uterus, and prostate) and other cancers were carried out. In 2010‐2012, 36 634 (42.4%), 38 048 (44.0%), and 11 774 (13.6%) patients were treated at national, prefectural, and nondesignated hospitals, respectively. The mortality hazard for all‐site cancer was significantly lower in national and prefectural designated hospitals (adjusted hazard ratio 0.60 [95% confidence interval, 0.53‐0.68] and 0.72 [0.66‐0.80], respectively) than in nondesignated hospitals. The adjusted 3‐year survival probabilities for all‐site cancer were 86.6%, 84.2%, and 78.8% in national, prefectural, and nondesignated hospitals, respectively. Site‐specific subgroup analyses revealed significantly lower hazard ratios in national and prefectural hospitals than in nondesignated hospitals for stomach, colorectal, lung, breast, and other cancers. To conclude, the majority of cancer patients underwent surgeries at designated hospitals and had higher 3‐year survival probabilities than those treated at nondesignated hospitals. Further centralization of patients from nondesignated to designated hospitals could improve population‐level survival., This study assessed the centralization of cancer surgery in Osaka, by comparing the number and 3‐year survival from diagnosis of patients treated at designated cancer care hospitals with those treated at nondesignated cancer care hospitals. More than 85% of patients underwent surgeries at designated cancer care hospitals, and their 3‐year survival probability was significantly higher than those treated at nondesignated cancer care hospitals. Further centralization of patients, considering the incidence and prognosis per cancer type and the existing health‐care system capabilities, could improve population‐level survival.

Published
2021

43. Classification of patients with esophageal eosinophilia by patterns of sensitization revealed by a diagnostic assay for multiple allergen-specific IgEs

Author

Yasuaki Nagami, Akinobu Nakata, Koichi Taira, Fumio Tanaka, Yasuhiro Fujiwara, Koji Otani, Shusei Fukunaga, Toshio Watanabe, Yuji Nadatani, Shuhei Hosomi, and Noriko Kamata

Subjects
Adult, Male, medicine.medical_specialty, アレルゲン, medicine.disease_cause, Immunoglobulin E, Gastroenterology, Statistics, Nonparametric, Allergic sensitization, 03 medical and health sciences, 0302 clinical medicine, Allergen, Japan, Internal medicine, medicine, Humans, Eosinophilia, 免疫グロブリンE, Eosinophilic esophagitis, Sensitization, Diagnostic panel, Retrospective Studies, biology, business.industry, Sensitization patterns, Middle Aged, respiratory system, Allergens, medicine.disease, Dysphagia, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cohort, 好酸球性食道炎, biology.protein, Female, Immunization, 030211 gastroenterology & hepatology, medicine.symptom, business
Abstract

Eosinophilic esophagitis (EoE) is considered to be an immunoglobulin E (IgE)-mediated allergic disorder. Our goal was to examine IgE-mediated allergic sensitization patterns in patients with esophageal eosinophilia (EE). We enrolled subjects with EE who underwent evaluation with a diagnostic panel to document multiple allergen-specific IgEs. Statistically significant groups were identified by cluster analysis. We also defined allergens based on their characteristics including outdoor, indoor, plant, and animal allergens. We classified patients with EE into 3 distinct groups, including cluster 1 (n = 62) who were minimally sensitized to most allergens except pollen and house dust, cluster 2 (n = 30) who were hypersensitized to outdoor and plant allergens, and cluster 3 (n = 15) who were hypersensitized to most allergens, most notably to indoor and animal allergens. Dysphagia reported among those in clusters 1, 2, and 3 at 35.5%, 46.7%, and 73.3%, respectively, (p = 0.028) and EoE endoscopic reference scores (EREFS) at 3.0, 6.0, and 8.0, respectively, (p

Published
2021

44. A Randomized Trial of Home Blood-Pressure Reduction by Alcohol Guidance During Outpatient Visits: OSAKE Study

Author

Yuya Akagi, Kei Kamide, Mai Kabayama, Shin Takiuchi, Ken Sugimoto, Koichi Yamamoto, Michio Tamatani, Ayumi Shintani, Yukako Nakata, Hiromi Rakugi, Jun Tomita, Atsuko Higuchi, and Naoko Wada

Subjects
Male, medicine.medical_specialty, hypertension, Original Contributions, Alcohol, Intervention group, 030204 cardiovascular system & hematology, law.invention, home morning blood pressure, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Internal Medicine, Ambulatory Care, Medicine, Humans, AcademicSubjects/MED00200, Morning, Ethanol, business.industry, 05 social sciences, blood pressure, Mean age, Middle Aged, Clinical trial, Treatment, Outpatient visits, Blood pressure, Treatment Outcome, chemistry, outpatient, AcademicSubjects/SCI00960, 0509 other social sciences, 050904 information & library sciences, business, alcohol guidance
Abstract

Background To evaluate the effectiveness of the nurse-led alcohol guidance to control home blood pressure (HBP) in the morning among male patients with hypertension during outpatient visits. Methods We enrolled 53 male patients with an HBP of ≥135/85 mm Hg with excessive drinking (alcohol ≥210 g/week or ≥60 g/day habitually) among outpatients in a randomized trial. Patients were assigned to a nurse-led alcohol guidance intervention or to the control. The primary outcomes were the mean HBP of 5 consecutive days at 6 months and alcohol consumption. Results Twenty-eight and 25 patients were randomized to intervention and control groups, respectively (mean age; 62.7 years old and 64.5, respectively). At baseline, the groups were well balanced across most characteristics. At 6 months, the mean HBP was 131/82 mm Hg in the intervention group vs. 145/87 mm Hg in the control group (SBP Conclusions We confirmed the effectiveness of the nurse-led alcohol guidance to control the HBP in male patients with hypertension during outpatient visits. Public trials registry number UMIN000017454 (UMIN Clinical Trials Registry).

Published
2021

45. [Coronary Artery Bypass Grafting via Partial Sternotomy Late after Partial Chest Wall Resection:Report of a Case]

Author

Kosuke, Nakata, Jun, Takaki, Kosaku, Nishigawa, Takashi, Yoshinaga, Ken, Okamoto, and Toshihiro, Fukui

Subjects
Male, Treatment Outcome, Coronary Artery Bypass, Off-Pump, Humans, Coronary Artery Bypass, Thoracic Wall, Sternotomy, Aged
Abstract

A 74-year-old man was referred to our department to receive coronary artery bypass grafting (CABG) because of severe triple vessel disease. He had undergone a chest wall resection including the right clavicle and the first and second ribs for the fibrosarcoma 40 years ago. The right internal thoracic artery was resected at the operation. Twenty-nine years after the operation, the plate used for the reconstruction of the chest wall was removed because of its infection. Off-pump CABG using left internal thoracic artery and vein grafts with lower partial sternotomy was successfully performed for the complete revascularization. This patient had a high possibility of sternum dehiscence and postoperative mediastinitis due to poor blood flow in the right upper sternum.

Published
2022

46. Short-term clinical outcomes of Kyocera Modular Limb Salvage System designed cementless stems for the endoprosthetic reconstruction of lower extremities: a Japanese Musculoskeletal Oncology Group multi-institutional study

Author

Satoshi Tsukushi, Yoshihiro Nishida, Takeshi Hirose, Eiji Nakata, Rumi Nakagawa, Jungo Imanishi, Tomoki Nakamura, Akihito Nagano, Hironari Tamiya, Takafumi Ueda, and Japanese Musculoskeletal Oncology Group

Subjects
Male, Reoperation, Cancer Research, Middle Aged, Limb Salvage, Prosthesis Design, Prosthesis Failure, Treatment Outcome, Japan, Lower Extremity, Oncology, Genetics, Humans, Neoplasm Recurrence, Local, Retrospective Studies
Abstract

Background The high rate of aseptic loosening of cemented stems has led to their frequent use in endoprosthetic reconstruction. However, problems, such as stem breakage and stress shielding at the insertion site, remain. The Japanese Musculoskeletal Oncology Group (JMOG) has developed Kyocera Modular Limb Salvage System (KMLS) cementless stems with a unique tapered press-fit and short fixation design. This study aimed to clarify the short-term postoperative outcomes of this prosthesis and validate the stem design. Methods One hundred cases of KMLS cementless stems (51 male patients; median age, 49 years; mean follow-up period, 35 months), with a minimum follow-up of 2 years, for the proximal femur (PF), distal femur (DF), and proximal tibia were prospectively registered for use. Prosthesis survival, complication rates, postoperative functional, and radiographical evaluation were analyzed. Complications or failures after insertion of the KMLS endoprostheses were classified into five types and functional results were analyzed according to the MSTS scoring system at postoperative 1 year. The diaphyseal interface and anchorage were graded by the ISOLS system at postoperative 2 years. Results The overall prosthesis survival rates at 2 and 4 years were 88.2 and 79.6%, respectively. The prosthesis-specific survival rate excluding infection and tumor recurrence was 90.2 and 87.9%, respectively. Younger age (p = 0.045) and primary tumor (p = 0.057) were associated with poor prognosis of prosthesis-specific survival excluding infection and tumor recurrence. Complications were observed in 31 patients, 13 patients underwent revision surgery. The mean MSTS functional score at 1 year postoperatively was 68%. Early implant loosening was significantly more common in the DF (p = 0.006) and PF/DF straight stem (p = 0.038). The ISOLS radiographic evaluation at 2 years after surgery revealed good bone remodeling and anchorage in most cases (bone remodeling: 90% / excellent and good, anchorage: 97% / excellent and good). Conclusions Tumor endoprosthesis long-term fixation to the diaphysis of the lower extremity remains challenging. The KMLS cementless stem with a unique tapered press fit design showed good short-term results in maintaining bone stock. To prevent early loosening, a curved stem should be used in PF and DF, but long-term follow-up is necessary.

Published
2022

47. Pilot study of an artificial intelligence-based deep learning algorithm to predict time to castration-resistant prostate cancer for metastatic hormone-naïve prostate cancer

Author

Wataru Nakata, Hideo Mori, Goh Tsujimura, Yuichi Tsujimoto, Takayoshi Gotoh, and Masao Tsujihata

Subjects
Male, Prostatic Neoplasms, Castration-Resistant, Cancer Research, Deep Learning, Oncology, Artificial Intelligence, Androgens, Humans, Androgen Antagonists, Pilot Projects, Radiology, Nuclear Medicine and imaging, General Medicine
Abstract

The object in this study is to develop an artificial intelligence-based deep learning algorithm for prediction of time to castration-resistant prostate cancer by combined androgen blockade therapy in metastatic hormone-naïve prostate cancer. We included 180 metastatic hormone-naïve prostate cancer patients who initially received combined androgen blockade. We first evaluated whether time to castration-resistant prostate cancer was a significant prognostic factor. Then, using the patients’ needle-biopsy specimen images, we developed and validated our deep learning algorithm. The results are shown below. First, we confirmed that time to castration-resistant prostate cancer correlated with overall survival (P 24 months (n = 18) and

Published
2022

48. Clinical and microbiological features of obstructive cholangitis with bloodstream infection caused by Pandoraea apista identified by MALDI-TOF mass spectrometry and ribosomal RNA sequencing in a cancer patient

Author

Naoya Itoh, Nana Akazawa, Yuichi Ishibana, Toshiki Masuishi, Akinobu Nakata, and Hiromi Murakami

Subjects
Male, Cystic Fibrosis, Burkholderiaceae, Cholangitis, Sequence Analysis, RNA, Bacteremia, Middle Aged, Infectious Diseases, RNA, Ribosomal, RNA, Ribosomal, 16S, Sepsis, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Humans, Colorectal Neoplasms
Abstract

Background Pandoraea species are multidrug-resistant glucose-nonfermenting gram-negative bacilli that are usually isolated from patients with cystic fibrosis (CF) and from water and soil. Reports of diseases, including bloodstream infections, caused by Pandoraea spp. in non-CF patients are rare, and the clinical and microbiological characteristics are unclear. The identification of Pandorea spp. is limited by conventional microbiological methods and may be misidentified as other species owing to overlapping biochemical profiles. Here, we report the first case of obstructive cholangitis with bacteremia caused by Pandoraea apista in a patient with advanced colorectal cancer. A 61-year-old man with advanced colorectal cancer who underwent right nephrectomy for renal cell carcinoma 4 years earlier with well-controlled diabetes mellitus was admitted to our hospital with fever for 2 days. The last chemotherapy (regorafenib) was administered approximately 3 weeks ago, and an endoscopic ultrasound-guided hepaticogastrostomy was performed 2 weeks ago under hospitalization for obstructive jaundice. Two days prior, he presented with fever with chills. He was treated with piperacillin-tazobactam for obstructive cholangitis and showed improvement but subsequently presented with exacerbation. Bacterial isolates from the blood and bile samples were identified as P. apista using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S ribosomal RNA sequencing. Based on the susceptibility results of the isolates, he was successfully treated with oral trimethoprim-sulfamethoxazole 160 mg/800 mg/day for 14 days for P. apista infection. Conclusions Pandoraea species are often misidentified. Therefore, multiple approaches should be used to identify them, and decisions regarding antimicrobial treatment should be based on actual in vitro susceptibility. Only seven cases of Pandoraea spp. bloodstream infections have been reported, and we report the first case of cholangitis with bacteremia.

Published
2022

49. Between-hospital variations in 3-year survival among patients with newly diagnosed gastric, colorectal, and lung cancer

Author

Toshitaka Morishima, Sumiyo Okawa, Shihoko Koyama, Kayo Nakata, Takahiro Tabuchi, and Isao Miyashiro

Subjects
Male, Survival Rate, Lung Neoplasms, Multidisciplinary, Humans, Colorectal Neoplasms, Hospitals, Retrospective Studies
Abstract

Due to increases in cancer survivability, quality assessments of cancer care must include long-term outcomes. This multicenter retrospective cohort study evaluated between-hospital variations in the 3-year survival rates of patients with gastric, colorectal, and lung cancer irrespective of treatment modality. We linked cancer registry data and administrative data from patients aged 18–99 years who were diagnosed with gastric, colorectal, or lung cancer between 2013 and 2015 in Osaka Prefecture, Japan. The 3-year survival rates were adjusted for potential prognostic factors using multilevel logistic regression models. Between-hospital variations were visually evaluated using funnel plots. We analyzed 10,296 gastric cancer patients from 30 hospitals, 9276 colorectal cancer patients from 30 hospitals, and 7978 lung cancer patients from 28 hospitals. The 3-year survival rate was 70.2%, 75.2%, and 45.0% for gastric, colorectal, and lung cancer, respectively. In the funnel plots, the adjusted survival rates of gastric and colorectal cancer for all hospitals lay between the lower and upper control limits of two standard deviations of the average survival rates. However, the adjusted survival rates of lung cancer for four hospitals lay below the lower limit while that for two hospitals lay above the upper limit. Older age, men, advanced cancer stage, comorbidities, functional disability, emergency admission, current/ex-smokers, and underweight were independently associated with poorer survival. In conclusion, there were between-hospital variations in 3-year survival for lung cancer even after adjusting for case mix. Quality improvement initiatives may be needed to raise the consistency of care.

Published
2022

50. Downregulation of connexin43 potentiates noradrenaline‐induced expression of brain‐derived neurotrophic factor in primary cultured cortical astrocytes

Author

Norimitsu Morioka, Syun Kondo, Tomoyo Takimoto, Yoshihiro Nakata, Yoki Nakamura, Nanase Harada, Nozomi Tokunaga, and Kazue Hisaoka-Nakashima

Subjects
Male, 0301 basic medicine, Small interfering RNA, Adrenergic receptor, Physiology, Primary Cell Culture, Clinical Biochemistry, Down-Regulation, Adrenergic, Stimulation, Norepinephrine, 03 medical and health sciences, 0302 clinical medicine, Neurotrophic factors, Receptors, Adrenergic, alpha-1, Receptors, Adrenergic, beta, medicine, Animals, Rats, Wistar, Extracellular Signal-Regulated MAP Kinases, Cells, Cultured, Cerebral Cortex, Brain-derived neurotrophic factor, Gene knockdown, Chemistry, Brain-Derived Neurotrophic Factor, Cell Biology, Cell biology, src-Family Kinases, 030104 developmental biology, medicine.anatomical_structure, Animals, Newborn, Astrocytes, Connexin 43, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, cardiovascular system, Female, RNA Interference, sense organs, Signal Transduction, Astrocyte
Abstract

Decreased expression of brain-derived neurotrophic factor (BDNF) is involved in the pathology of depressive disorders. Astrocytes produce BDNF following antidepressant treatment or stimulation of adrenergic receptors. Connexin43 (Cx43) is mainly expressed in central nervous system astrocytes and its expression is downregulated in patients with major depression. How changes in Cx43 expression affect astrocyte function, including BDNF production, is poorly understood. The current study examined the effect of Cx43 knockdown on BDNF expression in cultured cortical astrocytes after stimulation of adrenergic receptors. The expression of Cx43 in rat primary cultured cortical astrocytes was downregulated with RNA interference. Levels of messenger RNAs (mRNAs) or proteins were measured by real-time PCR and western blotting, respectively. Knockdown of Cx43 potentiated noradrenaline (NA)-induced expression of BDNF mRNA in cultured astrocytes. NA treatment induced proBDNF protein expression in astrocytes transfected with small interfering RNA (siRNA) targeting Cx43, but not with control siRNA. This potentiation was mediated by the Src tyrosine kinase-extracellular signal-regulated kinase (ERK) pathway through stimulation of adrenergic α1 and β receptors. Furthermore, the Gq/11 protein-Src-ERK pathway and the G-protein coupled receptor kinase 2-Src-ERK pathway were involved in α1 and β adrenergic receptor-mediated potentiation of BDNF mRNA expression, respectively. The current studies demonstrate a novel mechanism of BDNF expression in cortical astrocytes mediated by Cx43, in which downregulation of Cx43 increases, through adrenergic receptors, the expression of BDNF. The current findings indicate a potentially novel mechanism of action of antidepressants, via regulation of astrocytic Cx43 expression and subsequent BDNF expression.

Published
2021

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