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Approximately 1% of the general male population has azoospermia, and nonobstructive azoospermia accounts for the majority of cases. The causes vary widely, including chromosomal and genetic abnormalities, varicocele, drug‐induced causes, and gonadotropin deficiency; however, the cause is often unknown. In azoospermia caused by hypogonadotropic hypogonadism, gonadotropin replacement therapy can be expected to produce sperm in the ejaculate. In some cases, upfront varicocelectomy for nonobstructive azoospermia with varicocele may result in the appearance of ejaculated spermatozoa; however, the appropriate indication should be selected. Each guideline recommends microdissection testicular sperm extraction for nonobstructive azoospermia in terms of successful sperm retrieval and avoidance of complications. Sperm retrieval rates generally ranged from 20% to 70% but vary depending on the causative disease. Various attempts have been made to predict sperm retrieval and improve sperm retrieval rates; however, the evidence is insufficient. Further evidence accumulation is needed for salvage treatment in cases of failed sperm retrieval. In Japan, there is inadequate provision on the right to know the origin of children born from artificial insemination of donated sperm and the rights of sperm donors, as well as information on unrelated family members, and the development of these systems is challenging. In the future, it is hoped that the pathogenesis of nonobstructive azoospermia with an unknown cause will be elucidated and that technology for omics technologies, human spermatogenesis using pluripotent cells, and organ culture methods will be developed. [ABSTRACT FROM AUTHOR]

Cytokinesis, the final process of cell division, involves the accumulation of actin and myosin II filaments at the cell's equator, forming a contractile ring that facilitates the division into two daughter cells. While light microscopy has provided valuable insights into the molecular mechanism of this process, it has limitations in examining individual filaments in vivo. In this study, we utilized transmission electron microscopy to observe actin and myosin II filaments in the contractile rings of dividing Dictyostelium cells. To synchronize cytokinesis, we developed a novel method that allowed us to visualize dividing cells undergoing cytokinesis with a frequency as high as 18%. This improvement enabled us to examine the lengths and alignments of individual filaments within the contractile rings. As the furrow constricted, the length of actin filaments gradually decreased. Moreover, both actin and myosin II filaments reoriented perpendicularly to the long axis during furrow constriction. Through experiments involving myosin II null cells, we discovered that myosin II plays a role in regulating both the lengths and alignments of actin filaments. Additionally, dynamin‐like protein A was found to contribute to regulating the length of actin filaments, while cortexillins were involved in regulating their alignment. [ABSTRACT FROM AUTHOR]

Background: Approximately 8%–12% of couples worldwide face infertility, with infertility of individuals assigned male at birth (AMAB) contributing to at least 50% of cases. Conventional semen analysis commonly used to detect sperm abnormalities is insufficient, as 30% of AMAB patients experiencing infertility show normal results in this test. From a genetic perspective, the assessment of sperm DNA fragmentation (SDF) is important as a parameter of sperm quality. Methods: In this narrative study, we review and discuss pathophysiological causes, DNA repair mechanisms, and management of high SDF. We then summarize literature exploring the association between SDF and reproductive outcomes. Main Findings: Recent systematic reviews and meta‐analyses have revealed a significant association between high SDF in AMAB individuals and adverse reproductive outcomes including embryo development, natural conception, intrauterine insemination, and in vitro fertilization. However, the association with live birth rates and pregnancy rates following intracytoplasmic injection remains inconclusive. The disparities among quantitative assays, inconsistent reference range values, absent high‐quality prospective clinical trials, and clinical heterogeneity in AMAB patients with elevated SDF represent the main limitations affecting SDF testing. Conclusion: The evaluation and management of SDF plays an important role in a subset of AMAB infertility, but widespread integration into clinical guidelines will require future high‐quality clinical trials and assay standardization. [ABSTRACT FROM AUTHOR]

Aim: Diabetic kidney disease (DKD), a chronic kidney disease caused by diabetes and other comorbidities, is the leading cause of end‐stage renal disease. The pathogenesis of DKD is diverse and influenced by various causes, some but not all of which cause proteinuria. Some factors such as hypertension can modify DKD. Therefore, the spectrum of DKD is difficult to elucidate and remains unsolved. This study aims to classify and characterize DKD. Methods: We examined autopsy specimens from type 2 diabetes mellitus (DM) (n = 44) and non‐DM (n = 21) groups. Results: The frequency of interstitial fibrosis and tubular atrophy was higher in patients with proteinuric DKD than in those with non‐proteinuric DKD. The presence of polar vasculosis was associated with hypertension in DKD. In addition, an unsupervised hierarchical clustering analysis revealed the spectrum of renal histopathology findings for more‐proteinuric and less‐proteinuric DKD. With changes in the diagnostic criteria for hypertension and advances in antihypertensive drugs, the pathogenesis of DKD may be changing. Furthermore, a decision tree model suggested how diabetes, hypertension, and dyslipidemia interacted in predicting the characteristics of DKD. Conclusion: Polar vasculosis is a good indicator of the presence of DM and hypertension. Furthermore, the histopathological and clinical spectrum of DKD were related to the interaction of diabetes, hypertension, and dyslipidemia. These histopathological and clinical results may help to show the range of patient characteristics when conducting clinical trials and could help to determine whether chronic kidney disease is caused by DM or some other cause. SUMMARY AT A GLANCE: The pathogenesis of diabetic kidney disease (DKD) is diverse and influenced by various causes. The authors indicated that polar vasculosis is a good indicator of the presence of diabetes and hypertension. They also suggested the spectrum of renal histopathological findings for more‐proteinuric and less‐proteinuric DKD. [ABSTRACT FROM AUTHOR]

Penile cancer is a rare cancer for which no medical guidelines have been established before in Japan. These guidelines aim to standardize, as much as possible, the therapeutic modality for penile cancer, for which empirical evidence is limited on a global scale, thereby bolstering therapeutic outcomes for patients with penile cancer. The new guidelines conform to the Minds Guide for Developing Clinical Practice Guidelines (2017) as much as possible. However, virtually no randomized comparative studies and meta‐analyses based on such randomized studies have been conducted. Therefore, only the findings available at present were listed after conducting an exhaustive literature review of items with extremely low evidence levels and for which bodies of evidence and grades of recommendation were not evaluated. Clinical questions were set for items with a relatively large number of studies, including retrospective studies. However, since it is virtually impracticable to summarize bodies of evidence by systematic reviews, recommendation grades and evidence levels were discussed and determined by the consensus panel of the Preparatory Committee. The following were outlined: epidemiological, pathological, diagnostic, therapeutic, follow‐up, and quality of life‐related findings. Additionally, seven clinical questions were established to determine recommendation grades and evidence levels. We hope that these guidelines will prove to be useful to medical professionals engaged in clinical practice related to penile cancer in Japan and anticipate that critical reviews of the guidelines will lead to further refinement of the next edition. [ABSTRACT FROM AUTHOR]

An intramolecular hydroacylation of olefins using carboxylic acids (CAs) has been developed. With the aid of a boronic acid, CAs can be used as acyl‐radical precursors in catalytic photoredox reactions driven by visible light. The CAs are easily converted into their corresponding cyclic ketones without the need to use any stoichiometric activating reagents. Mechanistic studies implied that the formation of an "ate" complex from the CA and boronic acid is crucial for the generation of the acyl radical equivalent from the unreactive carboxy group. [ABSTRACT FROM AUTHOR]

Aim: The actual status of fertility preservation treatments in the startup phase in Japan was investigated as a basis for discussing future directions. Methods: This study was conducted as "Research project to promote support of children and parenting 2016" which was supported by Ministry of Health in Japan with the approval of the institutional review board at St. Marianna University. Subjects of the survey were facilities registered with the Japan Society of Obstetrics and Gynecology as fertility preservation facilities, and facilities belonging to the Japan Association of Private Assisted Reproductive Technology Clinics and Laboratories. We provided questionnaires to survey both the medical care system and cases for which fertility preservation was implemented between 2006 and 2016. Results: Responses were obtained from 68 facilities (of the 64, 59 [92.2%] responded to the questionnaire and 9 clinics cooperated). Many facilities limited the cryopreservation of oocytes and ovaries to patients 40–41 years old and the use of eggs to patients 44–45 years old. In the patient survey, 812 cases of oocyte cryopreservation and 201 cases of ovarian tissue cryopreservation were performed during study period. Breast cancer was the most indicated disease, with oocyte cryopreservation in the late 30s and ovarian tissue cryopreservation in the early 30s. Very few babies were born from fertility preservation, and no live birth cases of ovarian tissue cryopreservation were identified. Conclusions: Even from the early days, fertility preservation was implemented according to certain standards in Japan, but was characterized by a large variety of facilities. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of keishibukuryogan, a traditional Kampo formula known to be an anti‐Oketsu (impaired microcirculation and non‐physiological blood congestion) drug, in combination with an anti‐oxidant for the treatment of varicoceles. Methods: We retrospectively analyzed 119 patients with palpable and subclinical varicoceles who were treated with 7.5 g/day of keishibukuryogan and 600 mg/day of tocopherol nicotinate. Their motile sperm concentrations at the start of medication and after 3 months were compared. As a subgroup analysis, a comparison test was carried out between patients with a high‐grade varicocele and those with a low‐grade varicocele. Results: The mean age of the study patients was 35.6 years. Among them, 17, 41, 44 and 17 had subclinical, grade 1, grade 2 and grade 3 varicoceles, respectively. Overall, the differences in motile sperm concentration (millions/mL) before and after treatment were not significant (median 0.58, 95% confidence interval −0.12 to 1.56; P = 0.115). The results of the subgroup analysis showed that the motile sperm concentration in patients with a low‐grade varicocele significantly increased (median 1.21, 95% confidence interval 0.45–2.47; P = 0.024); however, no significant improvements were seen in patients with a high‐grade varicocele. Conclusions: The results of the present study showed that the combination of keishibukuryogan and an anti‐oxidant had a limited effect on varicoceles, but they suggest that it is effective for the treatment of low‐grade varicoceles. [ABSTRACT FROM AUTHOR]

Klinefelter syndrome and monozygotic twins are both rare. The reports of monozygotic twins with Klinefelter syndrome to have undergone fertility treatment are uncommon. This case report describes a case of 30‐year‐old monozygotic adult twin brothers diagnosed with nonmosaic Klinefelter syndrome following the complaint of infertility. The result of semen analysis showed cryptozoospermia (very low sperm count) and azoospermia (zero sperm count) with physical findings and lifestyles being very similar. They both underwent microtesticular sperm extraction. One had successful sperm retrieval and achieved pregnancy through intracytoplasmic sperm injection, whereas the other did not. Testicular pathological findings showed Sertoli cell‐only syndrome. To the best of our knowledge, this is the first report on monozygotic adult twins both of whom underwent microtesticular sperm extraction and resulted in different outcomes. [ABSTRACT FROM AUTHOR]

Background: Newly emerging serious post‐treatment complications among young male cancer survivors involve fertility and sexual function, preventing them from pursuing a normal family life. Methods: We studied and summarized published studies that assess the relationship between cancer treatments and reduced spermatogenesis or sexual dysfunction. Main findings: Infertility often occurs because of anticancer therapies that impair spermatogenesis. While some patients postremission functionally recover fertility, others experience a decreased sperm count and azoospermia. Fertility‐preserving modalities are currently being promoted worldwide to preserve spermatogenesis following cancer therapy. Patients who can ejaculate and have sperm in their semen should cryopreserve semen. However, for patients who have never ejaculated before puberty or in whom spermatogenesis has not been established, testis biopsy is performed to collect and preserve sperm or germ cells. Fertility preservation is gaining popularity and requires continuous information dissemination to oncologists and cancer treatment professionals. Furthermore, male sexual dysfunction predominantly involves erectile dysfunction and ejaculation disorder. Conclusion: Although preventive and therapeutic methods for these disorders have been established within urology, patients and medical professionals in other fields remain uninformed of these advances. Therefore, dissemination of information regarding fertility preservation techniques should be accelerated.Young male patients treated for cancer may experience decreased fertility and sexual function after treatment. This article described the causes of these failures and countermeasures. [ABSTRACT FROM AUTHOR]

Glia maturation factor (GMF) has been established as an inactivating factor of the actin‐related protein 2/3 (Arp2/3) complex, which regulates actin assembly. Regulation of actin assembly and reorganization is crucial for various cellular events, such as cell migration, cell division, and development. Here, to examine the roles of ADF‐H domain‐containing protein (also known as glia maturation factor; GmfA), the product of a single GMF homologous gene in Dictyostelium, gmfA‐null cells were generated. They had moderate defects in cell growth and cytokinesis. Interestingly, they showed a keratocyte‐like fan shape with a broader pseudopod, where Arp3 accumulated at higher levels than in wild‐type cells. They migrated with higher persistence, but their velocities were comparable to those of wild‐type cells. The polar pseudopods during cell division were also broader than those in wild‐type cells. However, GmfA did not localize at the pseudopods in migrating cells or the polar pseudopods in dividing cells. Adhesions of mutant cells to the substratum were much stronger than that of wild‐type cells. Although the mutant cells showed chemotaxis comparable to that of wild‐type cells, they formed disconnected streams during the aggregation stage; however, they finally formed normal fruiting bodies. These results suggest that GmfA plays a crucial role in cell migration. [ABSTRACT FROM AUTHOR]

Purpose: In this pilot study, the authors compared the effects of antioxidant co‐supplementation therapy and methylcobalamin therapy in patients with impaired semen quality. Methods: Eighty‐four subjects who visited male infertility clinics and showed abnormal semen test results were randomly subjected to one of the two therapies: antioxidant co‐supplementation therapy with vitamin C, vitamin E, coenzyme Q10, and flaxseed oil or methylcobalamin therapy. The oxidation–reduction potential (ORP) and 8‐hydroxy‐2′‐deoxyguanosine levels were used as indicators of oxidative stress levels in semen. Semen analysis was also performed. Results: The authors obtained results from 67 patients who had completed 3 months of treatment. Neither antioxidant co‐supplementation therapy nor methylcobalamin therapy changed the semen parameters significantly (except for the sperm concentration, which was increased by the latter therapy). When the pre‐treatment ORP value in semen was higher than the cutoff value, both therapies significantly increased the sperm concentration. The 8‐hydroxy‐2′‐deoxyguanosine level did not yield any meaningful predictive value with regard to increased sperm concentrations. Conclusions: Both antioxidant co‐supplementation therapy and methylcobalamin therapy increased the sperm concentration in patients with impaired semen quality when the basal ORP levels in their semen were elevated. [ABSTRACT FROM AUTHOR]

Background: As Japan's population continues to age, it is estimated that the number of people aged ≥75 years will exceed 20 million by 2025. Furthermore, over the past 10 years, we have not reduced the difference between life expectancy and healthy life expectancy. Therefore, the extension of healthy life expectancy and the development of a healthy society are the most urgent issues. In terms of medical care, the changing times have inevitably led to changes in disease structures and medical demands; therefore, the medical delivery system has had to be changed to meet these demands. As dementia rapidly increases, it is important to address "frailty," a condition in which people become more vulnerable to environmental factors as they age, and there is a need to provide services to older people, particularly the old‐old, that emphasize quality of life in addition to medical care. To realize a super‐aged society that will remain vigorous and vibrant for many years, we need to rethink the future of Japanese medicine and healthcare, and the state of society. Current situation and problems: Disparity between healthy life expectancy and average life expectancy in the realization of a healthy societyIt is a challenge to build a society with a long and healthy life expectancy through comprehensive prevention and management of lifestyle‐related diseases, as well as the elucidation of the factors that explain sex differences in healthy life expectancy, based on the recognition that lifestyle‐related diseases in midlife are risk factors for frailty and dementia in old age.Challenges in medical care for building a super‐aged and healthy societyThe challenges include promoting clinical guidelines suitable for older people, including lifestyle‐related disease management, promoting comprehensive research on aging (basic research, clinical research and community collaboration research), and embodying a paradigm shift from "cure‐seeking medical care" to "cure‐ and support‐seeking medical care." Furthermore, the key to the future of integrated community care is the development of a comprehensive medical care system for older people in each region and the development of the next generation of medical personnel.Dissemination of frailty prevention measures in a super‐aged societyThe concept of frailty encompasses the meaning of multifacetedness and reversibility; therefore, a comprehensive approach is required, including the renewal of conventional prevention activities in each region, such as the nutritional status of older people, physical activity including exercise, and various opportunities for social participation and participation conditions.Challenges of an unstable diet and undernutrition in older peopleAccording to the National Health and Nutrition Examination Survey of Japan, energy and protein intakes are low in Japanese people aged ≥75 years; particularly in people aged ≥80 years, low and insufficient intake of nutrients are prominent. Undernutrition in older people is increasing and is more pronounced in women. There are multiple factors behind this, including social factors, such as living alone, eating alone, poverty and other social factors, as well as problems with access to food security.Pharmacotherapy for older people: measures against polypharmacyIn addition to the problems of adverse drug events, drug interactions, duplication of effects and the presence of drugs that "require particularly careful administration," it is also necessary to take measures against polypharmacy in older people, as well as medical economic issues, such as high drug costs and large amounts of remaining drugs. Barriers to this measure include multiple medical institution visits for each disease, lack of coordination between professions, and lack of understanding by patients and families.Role of local communities in a healthy societyThe decline in the working‐age population is also a major challenge; however, we need to make a shift to use this declining birthrate and aging population as an opportunity rather than a crisis. As we look ahead to the coming of the 100‐year age of life, we rethink the creation of a comprehensive society and community, and aim to create an age‐free society where everyone can play an active role and live in peace, regardless of age. Contents of the proposal: In this report, we have put together a vision for the future of an aging Japanese society from a broader perspective of how the environment and local communities should be, rather than simply from the perspective of individual health. We aim to convey this proposal to the Ministry of Health, Labor and Welfare, the Ministry of Education, Culture, Sports, Science and Technology, the Cabinet Office, and various professional organizations.The paradigm shift from "cure‐seeking medical care" to "cure‐ and support‐seeking medical care" should be promoted for the development of a healthy societyWhile further promoting pre‐emptive medical care in the medical care for older people, the development of multidisciplinary medical guidelines appropriate for older people should be promoted at the same time. In addition, we should promote basic aging research, clinical research (including the long‐term care field) and transitional research that cover regional areas. Furthermore, while promoting the paradigm shift from "cure‐seeking medical care" to "cure‐ and support‐seeking medical care," the development of various comprehensive medical treatment systems for older people and the strengthening of integrated community care systems should be promoted.Development of the next generation of medical personnel to comprehensively deal with geriatric care, including training geriatric specialists, should be promotedAs the number of older people with multimorbidities and frailty rapidly increases in the future, we should promote the development of the next generation of medical personnel who can comprehensively handle medical care for older people, including training leading geriatricians in cooperation with multiple professions in the integrated community care system to provide sufficient medical care.Countermeasures for frailty in older people should be promoted from medical and community planning perspectivesTo address frailty, which requires comprehensive evaluation and intervention, the three pillars of frailty prevention (nutrition, exercise and social participation) should be incorporated and addressed as part of community development within each municipality, taking into account local characteristics. In particular, it is necessary to revise the way of thinking about nutrition management in older people and the guidelines of the societies in the field. In addition, it is important to strengthen industry–academia–government–private partnerships in each region, taking into account not only medical issues, but also social factors, and encourage the development of momentum in the entire region regarding measures against undernutrition in older people.Polypharmacy measures should be promoted in pharmacotherapy for older peopleIt is necessary to promote cooperation between physicians and pharmacists, establish other multiprofessional cooperation systems, and develop medical and long‐term care insurance systems to support this. It is also essential to change the public's mindset, and awareness‐raising activities at all levels are required, including the enhancement of educational materials for medical caregivers and the general public. In addition, the economic impact of healthcare using big data should be timely clarified.Innovation in medical and urban planning perspectives should be promotedIn the future, it will be necessary to modify and update multidisciplinary approaches such as social participation (e.g. participation in a salon) with a view to innovation in both medical care and community development, especially on the idea of a symbiotic community. In addition, industry–academia–government–private partnership is necessary, including all aforementioned, such as places where people can play an active role in the rest of their lives (such as employment), promotion of human connections, promotion of technology to support older people and support for daily life. Geriatr Gerontol Int 2021; 21: 601–613. [ABSTRACT FROM AUTHOR]

Obtaining a correct intraosseous epidermal cyst diagnosis is difficult due to the extreme rarity of this cyst. Further, the clinical manifestations and radiographic findings are very similar to those of a malignancy or infection. Early histopathological analysis is required for accurate diagnosis and for avoiding unnecessary antibiotic administration and amputation. [ABSTRACT FROM AUTHOR]

Background: Between 30% and 80% of patients with male infertility produce excessive reactive oxygen species (ROS) in their ejaculate even though the cause of male infertility is unexplained in approximately half of cases. The strong connection between oxidative stress (OS) and male infertility has led recent investigators to propose the term "Male Oxidative Stress Infertility (MOSI)" to describe OS‐associated male infertility. Methods: We searched the PubMed database for original and review articles to survey the effects of OS on male infertility, and then verified the effects and treatments. Main findings: Seminal plasma contains many antioxidants that protect sperm from ROS, because low amounts of ROS are required in the physiological fertilization process. The production of excessive ROS causes OS which can lower fertility through lipid peroxidation, sperm DNA damage, and apoptosis. Several assays are available for evaluating OS, including the MiOXSYS® analyzer to measure oxidation‐reduction potential. Several measures should be considered for minimizing OS and improving clinical outcomes. Conclusion: Accurately diagnosing patients with MOSI and identifying highly sensitive biomarkers through proteomics technology is vital for better clinical outcomes. [ABSTRACT FROM AUTHOR]

Efficient catalytic arsa‐Wittig reactions have been developed by using 1‐phenylarsolane as a catalyst. A wide array of aldehydes was converted to the corresponding olefins in high yields with moderate to excellent E stereoselectivity in the presence of a catalytic amount of 1‐phenylarsolane. Moreover, density functional theory calculations were carried out to afford insight into the E/Z selectivity. [ABSTRACT FROM AUTHOR]

Background: At present, one out of six couples is infertile, and in 50% of cases, infertility is attributed to male infertility factors. Genetic abnormalities are found in 10%‐20% of patients showing severe spermatogenesis disorders, including non‐obstructive azoospermia. Methods: Literatures covering the relationship between male infertility and genetic disorders or chromosomal abnormalities were studied and summarized. Main findings (Results): Genetic disorders, including Klinefelter syndrome, balanced reciprocal translocation, Robertsonian translocation, structural abnormalities in Y chromosome, XX male, azoospermic factor (AZF) deletions, and congenital bilateral absence of vas deferens were summarized and discussed from a practical point of view. Among them, understanding on AZF deletions significantly changed owing to advanced elucidation of their pathogenesis. Due to its technical progress, AZF deletion test can reveal their delicate variations and predict the condition of spermatogenesis. Thirty‐nine candidate genes possibly responsible for azoospermia have been identified in the last 10 years owing to the advances in genome sequencing technologies. Conclusion: Genetic testing for chromosomes and AZF deletions should be examined in cases of severe oligozoospermia and azoospermia. Genetic counseling should be offered before and after genetic testing. [ABSTRACT FROM AUTHOR]

[5]Radialene is known as an unstable cyclic hydrocarbon with a cross‐conjugated system. Incorporation of heteroatoms into [5]radialene skeleton is an effective strategy for stabilization. Herein we synthesized dithieno[3,4‐b:3',4'‐d]arsole (1) as a novel class of hetero[5]radialenes since trivalent arsenic atom is much more stable than phosphorus one, which was used for hetero[5]radialene but unstable in air. The characteristic nature of the arsa[5]radialene was experimentally and computationally studied by comparing with the isomer, dithieno[3,2‐b:2',3'‐d]arsole (2). Structural analysis by X‐ray crystallography and computational evaluation of aromaticity revealed the radialene character of 1. Interestingly, 1 showed phosphorescence though only fluorescence was observed for 2. Time‐dependent density functional theory (TD‐DFT) calculations implied that intersystem crossing could readily occur upon excitation for 1. Furthermore, it was computationally elucidated that dimerization and/or oligomerization via Diels‐Alder reaction, which convert [5]radialene, were circumvented to offer stability for 1. [ABSTRACT FROM AUTHOR]

Caged silsesquioxane (polyhedral oligomeric silsesquioxane: POSS) is an important class of organic‐inorganic hybrid molecules. The electronic properties of POSS have gradually attracted attention from experimental and computational perspectives, while POSS is generally utilized for reinforcement of polymer materials. Practical synthetic routes to access to aryl‐substituted POSS are effective tools for the systematic studies. Recently, we reported Rh‐catalyzed direct arylation of heptaisobutyl‐POSS with electron‐rich aryl iodides. Herein substrates for the Rh‐catalyzed direct arylation were widely examined: electron‐deficient, sterically‐hindered, and heteroatom‐containing aryl halides, and heptaphenyl‐POSS. Pd‐catalyzed direct arylation of POSS was developed as well. Notably, thiophene was introduced by the Pd‐catalyst, whereas the Rh‐system did not work for the substrate. In addition, the reaction mechanism of the Rh‐catalyzed reaction was elucidated by density functional theory calculations. [ABSTRACT FROM AUTHOR]

Objective: Urethral stenosis is a disease in which the lumen of the urethra becomes constricted by fibrosis. Such stenoses have been treated by urethral dilation using a bougie and optical internal urethrotomy (OIU). Recently, high‐pressure balloon dilation (BD) has been developed as a new treatment method for urethral stenosis. The present study compared the effectiveness of urethral dilation by BD and OIU. Methods: Twenty‐two patients of urethral stenosis were treated at Yokohama City University Medical Center between 2005 and 2015. Of these, 13 underwent BD, whereas OIU was performed in 9. BD was performed at 30 atm twice for 5 min each time. In OIU, an endoscopic knife was used to cut out the stenotic lesion in 3 directions. The endpoint was set as restenosis, which required additional surgical treatment, including BD, OIU, and the use of a urethral bougie. Results: The causes of urethral stricture were endoscopic surgery (n = 7; 31.8%), development after total prostatectomy (n = 4; 18.2%), iatrogenic reasons associated with catheter insertion (n = 5; 22.7%), development after a prostate needle biopsy (n = 3; 13.6%), and unknown (n = 3; 13.6%). The site of the stenotic lesion site was the anastomosis (n = 3; 13.6%), bladder neck (n = 6; 27.3%), prostatic urethra (n = 4; 18.2%), anterior urethra (n = 7; 31.8%), and membranous urethra (n = 2; 9.1%). The stenosis‐free rate was 84% for those undergoing BD and 22% for those receiving OIU. The median stenosis‐free time was significantly longer after BD than OIU (1675 vs. 244 days, respectively; P < .01). Conclusion: The stenosis‐free time was significantly longer after BD than OIU. [ABSTRACT FROM AUTHOR]

Aim: Neutrophil extracellular traps play key roles in the necrotizing vasculitis associated with anti‐neutrophil cytoplasmic antibody‐associated vasculitis (AAV). However, the relationships between neutrophil extracellular traps formation and the distribution and phase of vasculitis are not well understood. In the present study, we clarified the clinicopathological characteristics of older AAV patients, as well as the expression of citrullinated histone H3 (citH3), a marker of neutrophil extracellular traps, in autopsied AAV patients. Methods: We reviewed autopsy cases that were carried out at Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan, from 2001 to 2018. The expression of citH3 was determined by immunostaining. Results: AAV patients (six cases) were elderly (aged 73–94 years; three men and three women; myeloperoxidase anti‐neutrophil cytoplasmic antibody‐positive, five cases; proteinase‐3 anti‐neutrophil cytoplasmic antibody‐positive, one case; disease duration was 1.5–5.5 months; and patients were treated with steroids. All patients had necrotizing vasculitis in the medium‐to‐small‐sized vessels in various organs, and also severe vasculitis‐associated lesions including brain hemorrhage, alveolar bleeding, interstitial pneumonia, crescentic nephritis, acute pancreatitis and gastrointestinal bleeding. Expression of citH3 was associated with the activity of inflammation. Conclusions: We report severe clinicopathological characteristics of AAV in older patients. Expression of citH3 was a useful marker to evaluate vasculitis severity. Identification of these features might aid in the diagnosis of AAV. Geriatr Gerontol Int 2019; 19: 259–264. [ABSTRACT FROM AUTHOR]

Boyd et al. reported that only 8.7% of localized PC patients were informed about the possibility of future male-infertility before PC treatment.[2] Most PC patients are relatively aged and most physician tend to avoid about discussing it with their patients. Abbreviations & Acronyms PC prostate cancer YCUMC Yokohama City University Medical Center TESE testicular sperm extraction Male-fertility preservation - sperm cryopreservation is a gold standard for male-fertility preservation - has been paid attention for cancer patients over the past two decades because significant cancer treatment increasing cancer survivors and leading demand for future parenthood.[1] Unfortunately, prostate cancer (PC) patients are not adequately informed about treatment-induced infertility before PC treatment although there were certain patients who hope fertility preservation.[2] In this study, we report real-world data about sperm cryopreservation before definitive therapy for early-stage PC at our institution. Therefore, physician should inform about possibility of male-infertility due to PC treatment and discuss about sperm cryopreservation before PC treatment with patients who hope male-fertility preservation. [Extracted from the article]

The article discusses a study focusing on paediatric B-cell precursor acute lymphoblastic leukaemia (B-ALL) and clinical significance of adaptor protein SH2B3 (LNK) expression in it. Topics discussed include the determination of SH2B3 mRNA expression level in the study; the frequency of IKZF1 deletion in the patients under study; and the rate of event-free survival (EFS) in patients under study.

Summary: Klinefelter syndrome is a condition in which a male patient has one Y chromosome and one or more extra X chromosomes. It is the most common sex chromosome disorder. Klinefelter syndrome is distinguished by many clinical features, such as infertility, high gonadotropin and low testosterone levels, increased height, and sparse body and facial hair. We report the case of a 32‐year‐old man who visited our hospital complaining of male infertility. Semen analysis showed azoospermia, and chromosomal analysis revealed a 47,XY,i(X)(q10) karyotype, which is a rare variant of Klinefelter syndrome. No spermatozoon was found on microdissection testicular sperm extraction, and the testis biopsy histology showed only Sertoli cells and hyalinised seminiferous tubules. 47,XY, i(X)(q10) has an additional isochromosome made of the long arm of the X chromosome, which shares some features of classical Klinefelter syndrome in many aspects, but patients are usually shorter than average height and have normal intelligence. In addition, to the best of our knowledge, no successful sperm extractions from 47,XY, i(X)(q10) patients were reported in the literature. The reports of patients who have undergone microdissection testicular sperm extraction are very rare. Further reports and studies of this chromosomal abnormality are needed. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Lenalidomide has been developed as the derivative of thalidomide that has fewer side effects. We herein report a rare case of castration‐resistant prostate cancer successfully maintained using lenalidomide for multiple myeloma. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To investigate the incidence, etiology, treatment indications, and outcomes regarding infertile male patients in Japan. Methods: Between April, 2014 and March, 2015, the authors contacted 47 clinical specialists in male infertility who had been certified by the Japan Society for Reproductive Medicine. The participating clinicians were sent a questionnaire regarding information on their infertile patients, according to etiology and the number and success rates of male infertility operations that had been performed in their practice. Results: Thirty‐nine specialists returned the questionnaire and provided information regarding 7268 patients. The etiology of infertility included testicular factors, sexual disorders, and seminal tract obstruction. During the study year, the clinicians performed varicocelectomies, testicular sperm extractions (TESEs), and re‐anastomoses of the seminal tract. The rate of successful varicocelectomies was >70%. The sperm retrieval rates with conventional TESE and microdissection TESE were 98.3% and 34.0%, respectively, while the patency rates with vasovasostomy and epididymovasostomy were 81.8% and 61.0%, respectively. Conclusion: Surgical outcomes for infertile male patients are favorable and can be of great clinical benefit for infertile couples. To achieve this, urologists should work in collaboration with gynecological specialists in order to optimize the treatment of both partners. [ABSTRACT FROM AUTHOR]

Purpose To determine whether reactive oxygen species ( ROS) in semen samples could be measured with the Monolight™ 3010 Luminometer. Methods Using the Monolight™ 3010 Luminometer, the ROS was measured in the unprocessed semen samples of infertile male patients, as well as the luminescence of 190 semen samples. The samples were classified as 'luminescence-detectable' (n = 89) and 'luminescence-undetectable' (n = 101). Thereafter, the luminescence of the semen samples that had been obtained from the 715 infertile patients was measured and compared by using Sperm Motility Analyzing System measurements. Moreover, in order to investigate the ROS measurement consistency, the chemiluminescence values of 84 samples were measured concurrently by using the Monolight™ 3010 Luminometer and the 1251 Luminometer™. Results The semen volume, sperm motility, and progressive motility of the samples were significantly higher in the luminescence-undetectable samples. The sperm motility, straight-line velocity, curvilinear velocity, mean amplitude head displacement, beat cross frequency, and progressive motility showed an inverse correlation with the logarithmic-transformed luminescence level in the luminescence-detected samples. The integrated chemiluminescence levels in the 84 samples were correlated. Conclusion The substance that was measured in the unprocessed semen with the Monolight™ 3010 Luminometer and stimulated chemiluminescence is ROS. [ABSTRACT FROM AUTHOR]

Although a terminal oxyl species bound to certain metal ions is believed to be the intermediate for various oxidation reactions, such as O−O bond generation in photosystem II (PSII), such systems have not been characterized. Herein, we report a stable ZnII–oxyl species induced by an MFI-type zeolite lattice and its reversible reactivity with O2 at room temperature. Its intriguing characteristics were confirmed by in situ spectroscopic studies in combination with quantum-chemical calculations, namely analyses of the vibronic Franck–Condon progressions and the ESR signal features of both ZnII–oxyl and ZnII–ozonide species formed during this reversible process. Molecular orbital analyses revealed that the reversible reaction between a ZnII–oxyl species and an O2 molecule proceeds via a radical O–O coupling–decoupling mechanism; the unpaired electron of the oxyl species plays a pivotal role in the O−O bond generation process. [ABSTRACT FROM AUTHOR]

Although a terminal oxyl species bound to certain metal ions is believed to be the intermediate for various oxidation reactions, such as O−O bond generation in photosystem II (PSII), such systems have not been characterized. Herein, we report a stable ZnII-oxyl species induced by an MFI-type zeolite lattice and its reversible reactivity with O2 at room temperature. Its intriguing characteristics were confirmed by in situ spectroscopic studies in combination with quantum-chemical calculations, namely analyses of the vibronic Franck-Condon progressions and the ESR signal features of both ZnII-oxyl and ZnII-ozonide species formed during this reversible process. Molecular orbital analyses revealed that the reversible reaction between a ZnII-oxyl species and an O2 molecule proceeds via a radical O-O coupling-decoupling mechanism; the unpaired electron of the oxyl species plays a pivotal role in the O−O bond generation process. [ABSTRACT FROM AUTHOR]

Total internal reflection fluorescence microscopy revealed how individual bipolar myosin II filaments accumulate at the equatorial region in dividing Dictyostelium cells. Direct observation of individual filaments in live cells provided us with much convincing information. Myosin II filaments accumulated at the equatorial region by at least two independent mechanisms: (i) cortical flow, which is driven by myosin II motor activities and (ii) de novo association to the equatorial cortex. These two mechanisms were mutually redundant. At the same time, myosin II filaments underwent rapid turnover, repeating their association and dissociation with the actin cortex. Examination of the lifetime of mutant myosin filaments in the cortex revealed that the turnover mainly depended on heavy chain phosphorylation and that myosin motor activity accelerated the turnover. Double mutant myosin II deficient in both motor and phosphorylation still accumulated at the equatorial region, although they displayed no cortical flow and considerably slow turnover. Under this condition, the filaments stayed for a significantly longer time at the equatorial region than at the polar regions, indicating that there are still other mechanisms for myosin II accumulation such as binding partners or stabilizing activity of filaments in the equatorial cortex. [ABSTRACT FROM AUTHOR]

Aims/Introduction There is little information regarding how to use insulin degludec (D) when diabetic patients are preparing for total colonoscopy ( TCS). Materials and Methods A total of 12 patients with type 2 diabetes treated with insulin D and scheduled to undergo TCS were enrolled in the present study. A continuous glucose monitoring device was attached to each patient for 4 days, from two evenings before TCS to the morning after the procedure. The patients fasted for 24 h, starting after 18.00 h the day before TCS. Insulin D was only discontinued the morning of the day TCS was carried out. Results No patients experienced hypoglycemia during the daytime fasting period (08.00-18.00 h the day of TCS); the hypoglycemic index, mean glucose level, and standard deviation were 0, 141.3 ± 31.5 mg/ dL and 15.6 ± 6.5 mg/ dL. The mean glucose level and standard deviation during the daytime fasting period were significantly lower than during the daytime control period (08.00-18.00 h the day before TCS; P = 0.003, P = 0.001, respectively). The mean fasting glucose and fasting plasma glucose levels were significantly correlated ( r = 0.78, P = 0.002), as were both the mean glucose level and standard deviation during the daytime control period, and the change in the mean glucose level (fasting period minus control period; r = −0.79, P = 0.002, and r = −0.69, P = 0.01, respectively). Conclusions Patients can safely undergo TCS when insulin D is discontinued only once on the day of the procedure. [ABSTRACT FROM AUTHOR]

Aims/Introduction We aimed to identify factors - glycemic control, reactive inflammatory biomarkers or vital signs - associated with mortality in diabetic patients admitted to hospital for various infections (non-intensive care unit). Materials and Methods We retrospectively analyzed the cases of 620 diabetic patients admitted to hospital for various infections (non-intensive care unit) who underwent glucose monitoring >3 times per day. We extracted data regarding reactive inflammatory biomarkers and vital signs recorded on day 1 of hospital stay, and data on bacteremia and hypoglycemia status, glycemic variability ( GV; coefficient of variation and standard deviation) and mean glucose concentrations during the entire hospital stay. Univariate and stepwise multivariate logistic regression analyses were carried out to determine the association between these factors and mortality. Results The mortality rate was 10.1%. Reactive inflammatory biomarkers, vital signs and bacteremia were not associated with mortality. According to the results of the adjusted analysis, hypoglycemia showed a significant positive association with mortality, increasing death risk by 266% (odds ratio [ OR] 2.66, 95% confidence interval [95% CI] 1.22-5.83; P = 0.0006). High coefficient of variation and standard deviation values were significantly associated with increased mortality, increasing death risk by 18% ( OR 1.18, 95% CI 1.01-1.38; P = 0.03) and 9% ( OR 1.09, 95% CI 1.01-1.18; P = 0.03), respectively. Mean glucose concentrations were also significantly associated with mortality, increasing death risk by 5% ( OR 1.05, 95% CI 1.02-1.08; P = 0.0008). Conclusions Glycemic indices (especially hypoglycemia and GV), rather than reactive inflammatory biomarkers or vital signs, were associated with mortality in non-intensive care unit diabetes mellitus patients with infections. [ABSTRACT FROM AUTHOR]

Activating tyrosine kinase mutations or cytokine receptor signalling alterations have attracted attention as therapeutic targets for high-risk paediatric acute lymphoblastic leukaemia (ALL). We identified two novel kinase fusions, OFD1-JAK2 and NCOR1-LYN, in paediatric ALL patients with IKZF1 deletion, by mRNA sequencing. The patient with CSF2RA-CRLF2 also harboured IGH-EPOR. All these patients had high-risk features, such as high initial white blood cell counts and initial poor response to prednisolone. The functional analysis of these novel fusions is on-going to determine whether these genetic alterations can be targeted by drugs. [ABSTRACT FROM AUTHOR]

Background The demographic structure of a country changes dramatically with increasing trends toward general population aging and declining birth rates. In Japan, the percentage of the elderly population (aged ≥65 years) reached 25% in 2013; it is expected to exceed 30% in 2025 and reach 39.9% in 2060. The national total population has been decreasing steadily since its peak reached in 2008, and it is expected to fall to the order of 80 million in 2060. Of the total population, those aged ≥75 years accounted for 12.3% as of 2013, and this is expected to reach 26.9% in 2060. As the demographic structure changes, the disease structure changes, and therefore the medical care demand changes. To accommodate the medical care demand changes, it is necessary to secure a system for providing medical care. Japan has thus far attained remarkable achievements in medical care, seeking a better prognosis for survival; however, its medical care demand is anticipated to change both qualitatively and quantitatively. As diseases in the elderly, particularly in the old-old population, are often intractable, conventional medical care must be upgraded to one suitable for an aged society. What is required to this end is a shift from 'cure-seeking medical care' focusing on disease treatment on an organ-specific basis to 'cure and support-seeking medical care' with treatments reprioritized to maximize the quality of life ( QOL) for the patient, or a change from 'hospital-centered medical care' to 'community-oriented medical care' in correlation with nursing care and welfare. Current situation and problems Necessity for a paradigm shift to 'cure-and-support seeking medical care' In addition to the process of aging with functional deterioration of multiple organs, the elderly often suffer from systemically disordering diseases, such as lifestyle-related diseases, as well as geriatric syndrome and daily activity dysfunction; therefore, integrated and comprehensive medical care is required. In addition, with regard to diseases in the elderly, not only their acute stage, but also their chronic and intermediate stages must be emphasized in their treatment. Aiming to achieve a complete cure of disease by exploring the cause and implementing radical treatment, the conventional medical care model is difficult to apply to the medical care of the elderly; medical care suitable for the elderly is required., Spread of home-based care and the necessity for human resources development Many elderly people want to continue to live in their house and their community where they have been living for a long time, even with disease. There are increasing needs for QOL-emphasizing home-based care for patients in the intermediate stage after completion of acute stage treatment, or for end-of-life care. Hence, there is a demand for a shift to 'community-oriented medical care' for providing comprehensive care supported with medical and nursing resources available in the community. As the percentage of the elderly population (aged ≥65 years) and the availability of medical care resources vary considerably among different regions, it is important that specialists in the fields of public health, medical care, nursing care, and welfare work on establishing a collaborative system suitable for the local characteristics of each region by making the best use of their own specialties., Necessity for establishing a department of gerontology or geriatric medicine at each medical school In line with the increasing number of elderly people, it is necessary to upgrade the systems for educating and nurturing physicians engaged in healthcare and nursing care for the elderly. It is also necessary to develop the organic cooperation with other medical and nursing care professionals, such as registered nurses and care workers. At present, just approximately 30% of medical schools in Japan have a department specializing in medical care for the elderly and relevant medical education; there is an urgent need to improve the situation, as the majority of universities do not provide any such education., Necessity for establishing a medical center for promoting medical care provider collaboration, multidisciplinary training and a means to increase public awareness In the medical care for the elderly, comprehensive care must be provided from the viewpoints of both healthcare and nursing care; to improve the quality of such care services, multidisciplinary collaboration and team-based medicine are indispensable. Therefore, physicians, nurses, therapists, pharmacists, dieticians, care managers, and other health care professionals who have thorough knowledge about medical care for the elderly are of utmost necessity. In reality, however, the collaboration of these health care professionals is unsatisfactory, and the degree of understanding of team-based medicine by each medical professional is low. Therefore, as in the case of the establishment of cancer centers within individual regions to promote medical care for cancer, there is a demand to nurture professionals engaged in medical care for the elderly, and to establish a core facility for the promotion of multidisciplinary collaboration and team-based medicine for each region., Do the people understand the paradigm shift? Currently, not only healthcare professionals, but also many citizens seek 'cure-seeking medical care' aiming at a restoration of organ function; however, surveys of the elderly often show that they want to restore independent daily activity, rather than to achieve a 'cure.' In contrast, in the actual medical care setting, contradictory situations prevail in which the public awareness of the shift to 'cure-and-support seeking medical care' is unsatisfactory, including the fact that the majority of recipients of tertiary emergency care are elderly patients., Contents of the proposal The Science Council of Japan has the task to propose future visions for the Japanese aging society not only from the viewpoint of the health of each individual, but also from a broader perspective, taking into account the relationship between humans and society. Various issues related to general population aging are posing serious problems, which require prompt resolution. Although we made a number of proposals at the 21st Subcommittee for Aging, the situation has not changed satisfactorily. Accordingly, the present proposals on specific solutions were designed. In a super-aged society, a paradigm shift to 'cure-and-support seeking medical care' should be implemented A super-aged society will consist of an unprecedented demographic structure in which the percentage of only those people aged ≥75 years will increase in the entire population. Therefore, there is an urgent need to prepare for increasing populations of persons in need of long-term care and those who are likely to become in need of long-term care. Given the consideration that 'patients are not merely sick persons, but rather living persons,' a paradigm shift from conventional 'cure-seeking medical care' to 'cure and support-seeking medical care' must be implemented., Facilitate a paradigm shift to community-oriented medical care, and promote the activity of female physicians in the medical care for the elderly A paradigm shift should be promptly facilitated by reorganizing hospital functions and establishing a community comprehensive care system for home-based care to promote the participation of the elderly by themselves in care-supporting society. To further promote the collaboration of medical care and welfare, not only persons in charge of actual regional settings, but also university schools of medicine and regional core medical institutions experienced in medical care for the elderly should take the initiative to promote home-based care and facilitate a paradigm shift to community-oriented medical care. In addition, programs should also be developed to re-educate female physicians who became housewives in order to nurture them to become facilitators of geriatric medicine., Physicians who are required at local medical facilities must be nurtured through the establishment of a department of gerontology or geriatric medicine at each medical school To facilitate efficient medical care services, medical education and research, and human resources development in support of expected paradigm shifts, it is considered that a department of gerontology or geriatric medicine should be established at each medical school. Furthermore, it is necessary to allocate dedicated teachers of medical care for the elderly to all medical schools, as well as to upgrade practice-participatory drills and to collaborate with a broad range of entities, including local medical institutions, and welfare and nursing care facilities. Efforts must be made to nurture locally wanted physicians through specific efforts concerning team-based medicine., Promote the establishment of centers for geriatrics and gerontology (provisional name) for medical care collaboration, multidisciplinary training, and a means to increase public awareness To promote the uniform accessibility of expertise on efficient medical care that is best suited for a super-aged society, it is necessary to build a post-graduation educational system under the initiatives of the Japan Geriatrics Society and the National Center for Geriatrics and Gerontology across the nation in cooperation with regional medical schools and the Japan Medical Association. Furthermore, at least one hospital serving as a center for geriatrics and gerontology should be established in each regional block (Hokkaido, Tohoku, Koshinetsu, Hokuriku/Tokai, Kinki, Chushikoku and Kyushu/Okinawa) by making the best use of existing hospitals. By establishing these centers, uniform accessibility for the quality of medical care for the elderly in each region is expected., Public awareness should be raised to adapt to the paradigm shifts It is necessary to stimulate nationwide discussion on the significance for each citizen of paradigm shifts, such as from 'cure-seeking medical care' to 'cure and support-seeking medical care,' and from restoration of organ function to the maintenance and restoration of daily activity. To make the arguments more fruitful, the Japan Geriatrics Society and the National Center for Geriatrics and Gerontology should take the initiative of carrying out awareness-raising activity, and not only the medical world, but also the mass media, administration and the educational sector, from elementary to higher education, should play their respective roles. Geriatr Gerontol Int 2015; 15: 673-687. [ABSTRACT FROM AUTHOR]

A 42-year-old Japanese man developed Churg- Strauss syndrome 7 years after being diagnosed with chronic eosinophilic pneumonia. Prominent eosinophilia, subcutaneous nodules, and neuropathy in the left leg were seen. A pathological diagnosis of necrotizing vasculitis was determined by a biopsy of a subcutaneous nodule. The leg pain was severe and there was prominent atrophy of the thigh and calf, but the muscle weakness was mild. Serum anti-myeloperoxidase anti-neutrophil cytoplasmic antibody was positive. Because the initial treatment with an intravenous methylprednisolone pulse at 1 g/day for 3 days was not sufficient, a onetime treatment with intravenous cyclophosphamide at 15 mg/kg and intravenous immunoglobulin therapy ( IVIG) at 400 mg/kg/day for 5 days were administered. Peripheral eosinophilia improved and the leg pain significantly improved. IVIG was repeated 1 month later and symptoms gradually improved further. The early diagnosis of Churg- Strauss syndrome and the early initiation of IVIG with cyclophosphamide were thought to be important. [ABSTRACT FROM AUTHOR]

This study reviewed the clinical characteristics of 112 pediatric B-cell precursor acute lymphoblastic leukemia ( BCP- ALL) patients with TCF3- PBX1 fusion treated according to the Japan Association of Childhood Leukemia Study ( JACLS) ALL02 protocol ( n = 82) and Children's Cancer and Leukemia Study Group ( CCLSG) ALL 2004 protocol ( n = 30). The 3-year event-free survival ( EFS) and overall survival ( OS) rates were 85.4 ± 3.9% and 89.0 ± 3.5% in JACLS cohort, and the 5-year EFS and OS were 82.8 ± 7.0% and 86.3 ± 6.4% in CCLSG cohort, respectively, which are comparable to those reported in western countries. Conventional prognostic factors such as age at onset, initial white blood cell count, and National Cancer Institute risk have also no impact on OS in both cohorts. Surprisingly, the pattern of relapse in JACLS cohort, 9 of 82 patients, was unique: eight of nine patients relapsed during the maintenance phase and one patient had primary induction failure. However, bone marrow status and assessment of minimal residual disease on days 15 and 33 did not identify those patients. Interestingly, the two patients with IKZF1 deletion eventually relapsed in JACLS cohort, as did one patient in CCLSG cohort. International collaborative study of larger cohort is warranted to clarify the impact of the IKZF1 deletion on the poor outcome of TCF3- PBX1 positive BCP- ALL. [ABSTRACT FROM AUTHOR]