Tokai University Hachioji Hospital

Expanding elderly populations are a major social challenge in advanced countries worldwide and have led to a rapid increase in the number of elderly patients in intensive care units (ICUs). Innovative advances in medical technology have enabled lifesaving of patients in ICUs, but there remain various problems to improve their long-term prognoses. Post-intensive care syndrome (PICS) refers to physical, cognition, and mental impairments that occur during ICU stay, after ICU discharge or hospital discharge, as well as the long-term prognosis of ICU patients. Its concept also applies to pediatric patients (PICS-p) and the mental status of their family (PICS-F). Intensive care unit-acquired weakness, a syndrome characterized by acute symmetrical limb muscle weakness after ICU admission, belongs to physical impairments in three domains of PICS. Prevention of PICS requires performance of the ABCDEFGH bundle, which incorporates the prevention of delirium, early rehabilitation, family intervention, and follow-up from the time of ICU admission to the time of discharge. Diary, nutrition, nursing care, and environmental management for healing are also important in the prevention of PICS. This review outlines the pathophysiology, prevention, and future directions of PICS.

Should early surgery be conducted for asymptomatic patients with severe AR with an LVEF 50% and an LVESD index >25 mm/m 2 ? Early surgery may be considered for asymptomatic patients with severe AR with an LVEF 50% and an LVESD index >25 mm/m 2 .

IMPORTANCE: Prevention of atherosclerotic cardiovascular diseases is an important public health priority in Japan due to an aging population. OBJECTIVE: To determine whether daily, low-dose aspirin reduces the incidence of cardiovascular events in older Japanese patients with multiple atherosclerotic risk factors. DESIGN, SETTING, AND PARTICIPANTS: The Japanese Primary Prevention Project (JPPP) was a multicenter, open-label, randomized, parallel-group trial. Patients (N = 14,464) were aged 60 to 85 years, presenting with hypertension, dyslipidemia, or diabetes mellitus recruited by primary care physicians at 1007 clinics in Japan between March 2005 and June 2007, and were followed up for up to 6.5 years, with last follow-up in May 2012. A multidisciplinary expert panel (blinded to treatment assignments) adjudicated study outcomes. INTERVENTIONS: Patients were randomized 1:1 to enteric-coated aspirin 100 mg/d or no aspirin in addition to ongoing medications. MAIN OUTCOMES AND MEASURES: Composite primary outcome was death from cardiovascular causes (myocardial infarction, stroke, and other cardiovascular causes), nonfatal stroke (ischemic or hemorrhagic, including undefined cerebrovascular events), and nonfatal myocardial infarction. Secondary outcomes included individual end points. RESULTS: The study was terminated early by the data monitoring committee after a median follow-up of 5.02 years (interquartile range, 4.55-5.33) based on likely futility. In both the aspirin and no aspirin groups, 56 fatal events occurred. Patients with an occurrence of nonfatal stroke totaled 114 in the aspirin group and 108 in the no aspirin group; of nonfatal myocardial infarction, 20 in the aspirin group and 38 in the no aspirin group; of undefined cerebrovascular events, 3 in the aspirin group and 5 in the no aspirin group. The 5-year cumulative primary outcome event rate was not significantly different between the groups (2.77% [95% CI, 2.40%-3.20%] for aspirin vs 2.96% [95% CI, 2.58%-3.40%] for no aspirin; hazard ratio [HR], 0.94 [95% CI, 0.77-1.15]; P = .54). Aspirin significantly reduced incidence of nonfatal myocardial infarction (0.30 [95% CI, 0.19-0.47] for aspirin vs 0.58 [95% CI, 0.42-0.81] for no aspirin; HR, 0.53 [95% CI, 0.31-0.91]; P = .02) and transient ischemic attack (0.26 [95% CI, 0.16-0.42] for aspirin vs 0.49 [95% CI, 0.35-0.69] for no aspirin; HR, 0.57 [95% CI, 0.32-0.99]; P = .04), and significantly increased the risk of extracranial hemorrhage requiring transfusion or hospitalization (0.86 [95% CI, 0.67-1.11] for aspirin vs 0.51 [95% CI, 0.37-0.72] for no aspirin; HR, 1.85 [95% CI, 1.22-2.81]; P = .004). CONCLUSIONS AND RELEVANCE: Once-daily, low-dose aspirin did not significantly reduce the risk of the composite outcome of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction among Japanese patients 60 years or older with atherosclerotic risk factors. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00225849.

BACKGROUND: Satisfactory internal fixation of comminuted radial head fractures is often difficult to achieve, and radial head resection has been the accepted treatment. In this study, we compared the results of radial head resection with those of open reduction and internal fixation in patients with a comminuted radial head fracture. METHODS: Twenty-eight patients with a Mason type-III radial head fracture (some with associated injuries) were enrolled in the study. Fifteen patients underwent radial head resection as the initial treatment (Group I), and thirteen patients underwent open reduction and internal fixation (Group II). The age at the operation averaged 41.1 and 38.2 years, respectively, and the duration of follow-up averaged ten and three years, respectively. The outcomes were assessed on the basis of pain, motion, radiographic findings, and strength measured with Cybex testing. The overall outcome was rated with the functional rating score described by Broberg and Morrey and with the American Shoulder and Elbow Surgeons Elbow Assessment Form. RESULTS: Elbow motion averaged 15.5 degrees (extension loss) to 131.4 degrees (flexion) in Group I and 7.1 degrees to 133.8 degrees in Group II. The carrying angle and ulnar variance averaged 8.2 degrees and 1.9 mm in Group I and 1.5 degrees and 0.5 mm in Group II. Compared with Group II, Group I had a loss of strength in extension, pronation, and supination (p < 0.01). The Broberg and Morrey functional rating score averaged 81.4 points in Group I and 90.7 points in Group II (p = 0.0034). The score on the American Shoulder and Elbow Surgeons Elbow Assessment Form averaged 87.3 points in Group I and 94.6 points in Group II (p = 0.0031). CONCLUSIONS: The patients in whom the comminuted radial head fracture was treated with open reduction and internal fixation had satisfactory joint motion, with greater strength and better function than the patients who had undergone radial head resection. These results support a recommendation for open reduction and internal fixation in the treatment of this fracture.

INTRODUCTION: We examined the effectiveness of early rehabilitation for the prevention of postintensive care syndrome (PICS), characterised by an impaired physical, cognitive or mental health status, among survivors of critical illness. METHODS: We performed a systematic literature search of several databases (Medline, Embase and Cochrane Central Register of Controlled Trials) and a manual search to identify randomised controlled trials (RCTs) comparing the effectiveness of early rehabilitation versus no early rehabilitation or standard care for the prevention of PICS. The primary outcomes were short-term physical-related, cognitive-related and mental health-related outcomes assessed during hospitalisation. The secondary outcomes were the standardised, long-term health-related quality of life scores (EuroQol 5 Dimension (EQ5D) and the Medical Outcomes Study 36-Item Short Form Health Survey Physical Function Scale (SF-36 PF)). We used the Grading of Recommendations Assessment, Development and Evaluation approach to rate the quality of evidence (QoE). RESULTS: Six RCTs selected from 5105 screened abstracts were included. Early rehabilitation significantly improved short-term physical-related outcomes, as indicated by an increased Medical Research Council scale score (standardised mean difference (SMD): 0.38, 95% CI 0.10 to 0.66, p=0.009) (QoE: low) and a decreased incidence of intensive care unit-acquired weakness (OR 0.42, 95% CI 0.22 to 0.82, p=0.01, QoE: low), compared with standard care or no early rehabilitation. However, the two groups did not differ in terms of cognitive-related delirium-free days (SMD: -0.02, 95% CI -0.23 to 0.20, QoE: low) and the mental health-related Hospital Anxiety and Depression Scale score (OR: 0.79, 95% CI 0.29 to 2.12, QoE: low). Early rehabilitation did not improve the long-term outcomes of PICS as characterised by EQ5D and SF-36 PF. CONCLUSIONS: Early rehabilitation improved only short-term physical-related outcomes in patients with critical illness. Additional large RCTs are needed.

Ki67 index is now an essential part of classification of pancreatic neuroendocrine tumors. However, its adaptation into daily practice has been fraught with challenges related to counting methodology. In this study, three reviewers used four counting methodologies to calculate Ki67 index in 68 well-differentiated pancreatic neuroendocrine tumors: (1) 'eye-ball' estimation, which has been advocated as reliable and is widely used; (2) automated counting by image analyzer; (3) manual eye-counting (eye under a microscope without a grid); and (4) manual count of camera-captured/printed image. Pearson's correlation (R) was used to measure pair-wise correlation among three reviewers using all four methodologies. Average level of agreement was calculated using mean of R values. The results showed that: (1) 'eye-balling' was least expensive and fastest (average time <1 min) but had poor reliability and reproducibility. (2) Automated count was the most expensive and least practical with major impact on turnaround time (limited by machine and personnel accessibility), and, more importantly, had inaccuracies in overcounting unwanted material. (3) Manual eye count had no additional cost, averaged 6 min, but proved impractical and poorly reproducible. (4) Camera-captured/printed image was most reliable, had highest reproducibility, but took longer than 'eye-balling'. In conclusion, based on its comparatively low cost/benefit ratio and reproducibility, camera-captured/printed image appears to be the most practical for calculating Ki67 index. Although automated counting is generally advertised as the gold standard for index calculation, in this study it was not as accurate or cost-effective as camera-captured/printed image and was highly operator-dependent. 'Eye-balling' produces highly inaccurate and unreliable results, and is not recommended for routine use.

1 Current status of non‐pharmacotherapies in Japan Pacemaker treatment for bradyarrhythmia was first approved for national health insurance coverage in Japan in 1974, and its use rapidly became widespread thereafter. Approximately 40 years later, in 2017, the number of patients treated with this technology has increased to 60 137 (41 895 new cases and approximately 18 242 replacements). 5 Capsule‐shaped leadless pacemaker also became available in 2016, and this technology is being established as a new option. Non‐pharmacological treatment of tachy‐arrhythmia began in 1969 from when Will C. Sealy performed surgery in patients with Wolff‐Parkinson‐White (WPW) syndrome (Figure 1). Since then, the application of surgical treatment has expanded to conditions such as ventricular tachycardia (VT) and atrial fibrillation (AF), and surgery has been the pioneer of radical therapy for tachyarrhythmias. At the present time, many surgical methods have been replaced by catheter ablation; however, surgical treatment still remains an indispensable option for patients with a tachycardia resistant to other medical treatments. Open in a separate window FIGURE 1 History of non‐pharmacotherapy of cardiac arrhythmia

Butterflies are a diverse and charismatic insect group that are thought to have evolved with plants and dispersed throughout the world in response to key geological events. However, these hypotheses have not been extensively tested because a comprehensive phylogenetic framework and datasets for butterfly larval hosts and global distributions are lacking. We sequenced 391 genes from nearly 2,300 butterfly species, sampled from 90 countries and 28 specimen collections, to reconstruct a new phylogenomic tree of butterflies representing 92% of all genera. Our phylogeny has strong support for nearly all nodes and demonstrates that at least 36 butterfly tribes require reclassification. Divergence time analyses imply an origin ~100 million years ago for butterflies and indicate that all but one family were present before the K/Pg extinction event. We aggregated larval host datasets and global distribution records and found that butterflies are likely to have first fed on Fabaceae and originated in what is now the Americas. Soon after the Cretaceous Thermal Maximum, butterflies crossed Beringia and diversified in the Palaeotropics. Our results also reveal that most butterfly species are specialists that feed on only one larval host plant family. However, generalist butterflies that consume two or more plant families usually feed on closely related plants.

The original guideline for non-pharmacological treatments (cardiac implantable electronic device, catheter ablation, and arrhythmia surgery) of arrhythmias (Japanese Circulation Society [JCS] Guideline on Non-pharmacotherapy of Cardiac Arrhythmias) was first published in 2001, and there have been two revisions thereafter (2006 and 2011). The “JCS Guideline on Indications and Procedures for Catheter Ablation” was published in 2012 to cover the rapid development and expansion of catheter ablation techniques. Advances in non-pharmacological treatment of arrhythmia have further accelerated since then, with the succeeding emergence of new functions, usefulness, and evidence. Against the background of these remarkable developments, the guidelines needed to undergo many changes and revisions. Therefore, the format has been revised again to include cardiac implantable electronic devices and catheter ablation therapies. Since 2011, there has been a succession of innovative devices and treatment methods, such as (1) implantable cardiac monitoring, (2) subcutaneous implantable cardioverter-defibrillators, (3) wearable cardioverter-defibrillators, (4) remote monitoring, (5) magnetic resonance imaging-compatible devices, (6) leadless pacemakers, (7) balloon technology for pulmonary vein isolation, (8) percutaneous lead extraction, and (9) left atrial appendage closure devices. Thus, this revision needed to add new sections to accommodate these developments. In addition, new content on existing treatment methods has been added as much as possible, including hardware improvements, new evidence, and the challenge of reducing radiation exposure. Selecting and summarizing suitable information from the vast amount of available data within a limited space could have been a daunting task for all team members; however, our efforts have culminated in this guideline revision containing carefully selected and essential information, thanks to everyone who collaborated on this project. Two related guidelines (JCS Guideline on Treatment of Acute and Chronic Heart Failure, and JCS Guideline on Treatment of Genetic Arrhythmia) were each revised in 2018.1, 2 Some working group members participated in the revision of both guidelines, as team members or observers, thus ensuring consistency between the guidelines. Non-pharmacotherapy in the broad sense includes external cardioversion for atrial fibrillation and sustained ventricular tachyarrhythmias, temporary intravenous pacing, and percutaneous pacing. However, for details of these therapies, refer to the JCS Guidelines on Pharmacotherapy of Atrial Fibrillation3 and the Japan Resuscitation Council Guidelines.4 Pacemaker treatment for bradyarrhythmia was first approved for national health insurance coverage in Japan in 1974, and its use rapidly became widespread thereafter. Approximately 40 years later, in 2017, the number of patients treated with this technology has increased to 60 137 (41 895 new cases and approximately 18 242 replacements).5 Capsule-shaped leadless pacemaker also became available in 2016, and this technology is being established as a new option. Non-pharmacological treatment of tachy-arrhythmia began in 1969 from when Will C. Sealy performed surgery in patients with Wolff-Parkinson-White (WPW) syndrome (Figure 1). Since then, the application of surgical treatment has expanded to conditions such as ventricular tachycardia (VT) and atrial fibrillation (AF), and surgery has been the pioneer of radical therapy for tachyarrhythmias. At the present time, many surgical methods have been replaced by catheter ablation; however, surgical treatment still remains an indispensable option for patients with a tachycardia resistant to other medical treatments. As with surgical treatment, catheter ablation was initially performed for supraventricular tachycardias such as WPW syndrome. However, the revolutionary discovery of pulmonary vein isolation (PVI) for AF and the advent of three-dimensional (3D) navigation systems have subsequently resulted in a tremendous increase in the number of cases treated with catheter ablation. In 2016, >74 000 catheter ablation procedures were performed in Japan, of which >45 000 were implemented for AF.6 In 2015, a PVI method using cryoballoon ablation was introduced in Japan. Later, new techniques such as hot balloon or laser balloon (endoscopic systems using laser irradiation) ablation technologies entered the market, and safer and easier treatment methods are currently being established. In addition, prevention of systemic embolism using a left atrial appendage closure (LAAC) device is being established as a breakthrough treatment for AF patients who have difficulty in continuing anticoagulation therapy. Because early implantable cardioverter-defibrillators (ICDs) were highly invasive owing to the requirement for a thoracotomy, the indications for this treatment were highly limited. However, the development of transvenous leads, the discovery of the biphasic shock method, and a reduction in both the size and weight of the generator have now enabled implantation using the same technique as for pacemakers, which has contributed to expanding the application of ICDs to primary prevention. In 2017, approximately 6691 devices (4288 new cases, 2403 replacements) were implanted in Japan.5 The subcutaneous implantable cardioverter-defibrillator (S-ICD) was developed in 2015, and its clinical usage is progressing. In 2004, cardiac resynchronization therapy (CRT) became available for patients with impaired cardiac function, and the usefulness of this treatment has been verified. especially in heart failure patients with complete left bundle branch block in Japan. Because patients with heart failure have a high risk of sudden death, an ICD with a biventricular pacing function (CRT defibrillator [CRT-D]) was also developed and approved in 2006. In 2017, CRT was newly administered in 3321 patients in Japan, 2399 of whom (72%) received the CRT-D, demonstrating that the treatment has been actively applied to prevent sudden death.5 A wearable cardioverter-defibrillator (WCD) was introduced in Japan in 2015, which can be used for candidates for ICD therapy as a bridge treatment until application of an ICD is possible. Many devices are also equipped with a remote monitoring function, which sends most of the biological information and device data to the medical facility while the patient is staying at home by enabling the early detection of abnormal findings. As described above, there have been remarkable developments in the non-pharmacotherapy of arrhythmias. However, problems still remain, including (1) the risk of complications associated with aging of patients, (2) the requirement for high-quality training of specialists and medical staff to enable them to handle the expanding indications and diversifying treatment methods, (3) the overflow of information and increasing complexity of management because of the sophisticated and multiple functionalities of the devices, and (4) the impact of the expanding indications of expensive devices in the setting of limited medical resources. In the future, it will be necessary to formulate evidence unique to Japan on the extent to which cutting-edge non-pharmacological treatments for arrhythmias improve the prognosis of patients. This guideline recommends indications for non-pharmacotherapy of arrhythmia based on the latest findings and evidence. There is an increasing variety of non-pharmacotherapies, and extensive progress is being made in this field. This guideline contains information on conventional cardiac implantable electronic devices (CIEDs), such as pacemakers, ICDs, and ICDs with biventricular pacing function, as well as new information on remote monitoring, magnetic resonance imaging-conditional CIEDs, leadless pacemakers, percutaneous lead extraction, implantable monitors, S-ICDs, and WCDs. Information on catheter ablation includes radiation exposure, new 3D mapping systems, balloon ablation for AF, bipolar ablation, and chemical ablation. In addition, this guideline discusses the LAAC device for the first time, which is not a treatment for arrhythmia itself but for preventing thromboembolism – a serious problem associated with AF. Non-pharmacotherapy of arrhythmia is expected to increase in the future, so there is a need to standardize all non-pharmacotherapy processes, including not only treatment indications but also their theoretical background, recommended procedures, necessary equipment and implementation system, and precautions that have to be taken before and after the procedure. The indications of non-pharmacological treatments of tachyarrhythmia in children differ from those in adults, so there are many cautionary points to note. Therefore, CIEDs and catheter ablation for children are described under independent chapters, as in previous guidelines. The information on surgical treatment for arrhythmia mainly focuses on surgical treatment for AF and VT. Surgery for supraventricular tachycardia has been omitted from this guideline because the number of surgical procedures has dramatically decreased in recent years. Nevertheless, surgery is still indicated for some patients with supraventricular tachycardias, including those with unsuccessful ablation. The aim of this guideline is to clarify the indications, results, and complications of non-pharmacological treatments for arrhythmias such as bradyarrhythmia, supraventricular tachycardia, AF, premature ventricular contractions, VT, and ventricular fibrillation, as well as treatment for the associated heart failure and thromboembolism. We are striving for standardized treatment by explicitly describing the procedures. Specific information on the procedures is also included, such as the knowledge, equipment, and doctor/facility conditions required to perform the procedure. The guideline has been created based on evidence and consensus at the time of publication and should be updated over time. This guideline describes the recommended indications and procedures as of 2018. Future technological advances will further expand the indications for non-pharmacotherapy of arrhythmia and make the procedures more reliable and convenient. This guideline is designed to be used as a reference by doctors diagnosing and treating diseases in clinical practice, and the final decision should be made by the attending physicians after ascertaining the patient's condition. Even when selecting a diagnosis or treatment that does not follow the guideline, the decision of the attending physicians should be prioritized in consideration of the individual patient's situation. In actual clinical settings, it is most important for the attending physicians to make the judgment after fully considering the clinical background and social situation of each patient while complying with the guideline. For this guideline, we first surveyed materials based on evidence from the USA and Europe, then further critically examined the level of evidence, collected information available in Japan, and examined all materials based on the experiences and opinions of members and collaborators in the joint working group. The recommendation classes and evidence levels used in this guideline conform to those of the American Heart Association (AHA), American College of Cardiology (ACC), and Heart Rhythm Society (HRS) guidelines.7 The recommendation class of indications for each diagnosis and treatment method is classified as I, IIa, IIb, and III, and the level of evidence is classified into levels A, B, and C (Tables 1,2). The guideline also states the class of recommendation and level of evidence based on the “MINDS Handbook for Clinical Practice Guideline Development 2007”,8 published by the Medical Information Network Distribution Service (MINDS) Evidence-based Medicine dissemination promotion project as a guideline preparation method (Tables 3,4). The MINDS grades of recommendation are comprehensively determined, taking into account the following factors: (1) level of evidence, (2) amount and variation of evidence, (3) extent of clinical effectiveness, (4) clinical applicability (physician ability, regional characteristics, medical resources, insurance system, etc), and (5) evidence on harm and cost. Not recommended as evidence indicates that the treatment is ineffective or even harmful The MINDS level of evidence (levels of evidence in literature on treatment) is a classification based on research design, and the highest level was adopted when multiple papers were considered. This guideline describes both the conventional AHA/ACC/HRS guideline classifications and the MINDS classification, whenever possible, for the content of each diagnosis and treatment. However, the MINDS grade of recommendation and level of evidence should be used only as a reference, as this system regards the evidence level in a fundamentally different manner. This revision adds new knowledge acquired from advances in diagnostic techniques and treatment methods, or recently reported important evidence, while considering consistency with each of the previously reported guidelines published by the JCS Joint Working Group. Pacemaker therapy for bradyarrhythmia became covered by insurance in Japan in 1974. Initially, pacemakers only had ventricular pacing function; however, at present, pacemakers with functions such as maintaining atrioventricular synchrony with dual-chamber pacing modes, as well as monitoring atrioventricular conductivity to suppress right ventricular pacing, have been developed, which has contributed to improving patients’ prognosis. In 2017, a capsule-type leadless pacemaker appeared on the market, and its clinical application is progressing. An implantable cardioverter-defibrillator (ICD) was introduced in Japan in 1996 to treat fatal arrhythmias (ventricular tachycardia [VT]/ventricular fibrillation [VF]). Early ICDs were a highly invasive treatment requiring a thoracotomy, severely limiting their indications. However, the subsequent development of transvenous leads, discovery of the biphasic shock method, and reduction in the size and weight of the generator enabled use of the same technique as that for pacemaker implantation, which has greatly contributed to the expansion of indications for improving life prognosis and for primary prevention. The year 2000 saw the appearance of the dual-chamber ICD, which contributed to a dramatic improvement in pacing function during bradycardia, equivalent to that of a pacemaker for bradycardia, and a diagnostic algorithm based on atrial signal detection. Furthermore, the subcutaneous ICD (S-ICD) was introduced in 2015 and has been actively used for patients without venous access and/or those who do not require pacing functions. In 2004, biventricular pacing, or cardiac resynchronized therapy (CRT), became available for patients with impaired cardiac function, and its utility has been confirmed, especially in patients with heart failure who have desynchronous contractions due to complete left bundle branch block (CLBBB). As patients with heart failure are at a high risk of sudden death, an ICD with a biventricular pacing function (CRT-D) was developed and approved in 2006. Improved pacing-site selectivity with quadrupolar left ventricular leads, functions utilizing self-right bundle conduction, and multipoint left ventricular pacing have been applied in clinical practice and may reduce the number of non-responders. As of 2017, CRT-D has been indicated for 72% of new cardiac resynchronization therapy (CRT) cases in Japan; thus, aggressive prevention of sudden death is ongoing.5 ICDs have limited effectiveness after an acute myocardial infarction and at the early stage after the diagnosis of heart failure. In 2015, wearable cardioverter-defibrillators (WCDs) came into use to prevent sudden death during the waiting period while the indications for ICD are being determined. WCD is also used as a bridging treatment until the next implantation for patients whose ICD has been removed because of infection or other reasons. Many devices are equipped with a remote monitoring function, which now enables the early detection of abnormal findings related to device functions and biological characteristics. Furthermore, although their use is conditional, magnetic resonance imaging (MRI)-compatible devices has become to be recognized as ordinary function, which is particularly useful in Japan where the rate of installation and using MRI are high. Non-pharmacological treatment of arrhythmia requires advanced medical technology, and progress is rapid in this field. Physician and facility requirements are extremely important for the application of this guideline. This section describes the current facility standards and practitioner standards; however, as these may be revised in the future, refer to the Japanese Circulation Society or Japanese Heart Rhythm Society (HRS) websites to obtain the latest information. Each non-pharmacotherapy must be applied effectively and safely, and a system for responding to emergencies (human resource development, establishment of a team medical system, use of fully maintained equipment) is required. The following institutional standards and practitioner standards were proposed by the Japanese HRS in 2017, considering the novelty of the leadless pacemaker and that this procedure requires cardiac access via the femoral vein using a large sheath9 (see “3.7 Leadless pacemakers” in this chapter). Facility standards Practitioner standards The following practitioner standards were proposed by the Japanese HRS in 2016 for S-ICD implantation.11 Practitioner standards Clinical use of a WCD requires appropriate selection of cases and understanding of the equipment, and the following practitioner standards were proposed by the Japanese HRS in 2017.12 Practitioner standards ICMs may be implanted in any facility that satisfies the facility standards for pacemakers, ICD, or CRT-P/CRT-D as a condition for insurance application (based on the 2015 Medical Fee Points Table). When deciding on the indications for treatments that require advanced medical technology such as CIEDs, it is essential that the patient provides voluntary consent after receiving sufficient information. The information should be provided using words that the patient can understand, pursuant to the provisions of Chapter 1, Article 1-4, paragraph 2 of the Medical Care Act: “In the delivery of medical care, a physician, dentist, pharmacist, nurse, or other medical care professional shall give appropriate explanations and endeavor to foster understanding in the recipients of medical care.” The content of the explanation is based on the judgment according to the knowledge and experience of each doctor; however, it is necessary to provide the following information to the patient: (1) information on the disease (type and severity of arrhythmia, underlying heart disease, etc); (2) aim and details of the treatment (including device model and manufacturer name), therapeutic effect and success rate, complications (types, severity, and incidence) during the acute phase and during long-term follow-up (requires not only general information but also information on the performance in the facility in question), and the reason for selecting the treatment; (3) treatments other than the treatment in question (pharmacotherapies, other non-pharmacotherapies [including treatment available at other facilities]) and the therapeutic effect of those treatments; (4) expected results with monitoring alone without the treatment in question (predicted outcome and probability thereof); (5) positioning of the treatment in question for various arrythmias and possible unexpected complications (short-term and long-term); (6) cost of the treatment (including the cost of this treatment and other treatments); and (7) assurance that consent can be withdrawn before and during treatment. After the provision of the above information, if the patient requests opinions from other doctors or medical institutions (second opinion), then it is essential to respond to the request. The patient is the main person in the decision-making process, and the right of self-determination of the patient is the most important factor when deciding on indications for non-pharmacotherapy. Basically, the consent of the patient and/or the family is required, based on their understanding of the explanation provided by the medical staff involved in testing and treatment. If the patient is unable to express their intention or is a minor, a family representative or legal representative will act on their behalf. Ultimately, the signatures of all attendees, including the medical staff, are obtained. Normally, 2 copies of the information sheet are prepared. The original copy is generally kept in the patient's medical record and another copy is given to the patient. Physicians must be fully cognizant that informed consent is an important opportunity for the patients to compare and consider the benefits and disadvantages of the treatment, and to enable selection of treatment that is truly beneficial for them. The information must also be specific and easy to understand for the patients and their families. Complications with CIED implantation are due to the device itself (generators and/or leads), or the implantation procedure. Generator complications include malfunctions such as recalls and resets due to electromagnetic interference. Lead complications include malfunctions such as recalls, lead dislodgement and aging, pacing and venous and implantation techniques can reduce complications lead lead and from lead There are in the of CIED infection which is reported to from to of the ICD and CRT-D indications has resulted in increased implantation of the devices in patients patients with heart or and patients taking and/or as well as an increased number of due to long-term which the of is important to that implantation of a CIED is a surgical thus, it is necessary to fully understand the of infection and the and surgical and surgical and use of The Japanese Society of and the Japan Society for have proposed Guidelines for of for of particularly with to the use of As is also an infection complete is The of the the CIED is also The is created above the of the not in the subcutaneous to prevent of the If the subcutaneous containing the subcutaneous is it is recommended to a under the for lead can complications such as and Therefore, methods such as before and have been recommended to vein is over vein to prevent lead by the and the method is recommended not only to reduce the complications but also to prevent lead prevent to the and improve lead When the care should be taken to of the venous and myocardial The rate is reported to be and is by the use of on the of the lead after lead and lead is also important to understand the of the lead or including the condition of of the implanted pacing and should be As an early has a high who are taking or due to atrial fibrillation (AF), or disease are a and is particularly important in these patients. not only but can also device infection at a remote phase because it to and When is it is important to the of If there is of the and of or the is and can be with using However, and should be if the because of or if of by is performed because it the risk of There is in the of device and risk include heart of and other pulmonary disease, external pacemaker device and early device infection has it is necessary to the system, which a consideration is required and after and left to lead and and monitoring to early failure are also The and of the may after is necessary to the pacing and the of the before and the as is also recommended to before of patients who on life after should also be can which can pacing in pacemakers and therapy in A of electromagnetic has been published by the Japan can generally be used if the is not on and however, patients must be to a of from electromagnetic and from than home use of therapy equipment, is is needed when using rapid electronic equipment, and electronic The patient should be to from the if experience and have been reported to have an and medical care may be required to prevent interference. There are conditions to be for and patients with are required by to have a (see Chapter for patients with an The recent emergence of new devices has made management more There is also a that the of understanding of device functions will as patients become is important to provide patient using and to information on appropriate for possible CIED management is performed with device using the is necessary to not only the information of the device but also the general condition of the patient using various Specific information (1) (2) lead (3) pacing (4) and pacing (5) arrhythmia detection and treatment and (6) heart rate and information, The patient management is by at this information. In recent it has become possible to perform remote monitoring in most monitoring has been to be as as conventional and to enable the diagnosis of arrhythmia and Furthermore, and life prognosis have also been Therefore, remote monitoring for patients with CIEDs is highly and it is recommended to it as a management however, there are increased for There has been an increase in the number of patients implanted with CIEDs and in the aging to patients with CIEDs is required.

BACKGROUND: High-intensity focused ultrasound (HIFU) is a minimally invasive technique used in achieve coagulation necrosis. We evaluated biochemical disease-free survival rates, predictors of clinical outcome and morbidity in patients with localized prostate cancer treated with HIFU. METHODS: A total of 181 consecutive patients underwent HIFU with the use of Sonablate (Focus Surgery, Indianapolis, IN, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and pretreatment prostate-specific antigen (PSA) level were 70 years (range 44-88) and 9.76 ng/mL (range 3.39-89.60). A total of 95 patients (52%) were treated with neoadjuvant hormones. The median follow-up period for all patients was 18.0 months (range 4-68). RESULTS: The biochemical disease-free survival rates at 1, 3 and 5 years in all patients were 84%, 80% and 78%, respectively. The biochemical disease-free survival rates at 3 years for patients with pretreatment PSA less than 10 ng/mL, 10.01-20.0 ng/mL and more than 20.0 ng/mL were 94%, 75% and 35%, respectively (P<0.0001). Multivariate analysis identified pretreatment PSA (P<0.0001) as a independent predictor of relapse. CONCLUSION: High-intensity focused ultrasound therapy appears to be a safe and efficacious minimally invasive therapy for patients with localized prostate cancer, especially those with a pretreatment PSA level less than 20 ng/mL.

OBJECTIVE: To evaluate the biochemical disease-free survival (DFS), predictors of clinical outcome and morbidity of patients with localized prostate cancer treated with high-intensity focused ultrasound (HIFU), a noninvasive treatment that induces complete coagulative necrosis of a tumour at depth through the intact skin. PATIENTS AND METHODS: In all, 63 patients with stage T1c-2bN0M0 localized prostate cancer underwent HIFU using the Sonablate system (Focus Surgery, Inc., Indianapolis, IN, USA). None of the patients received neoadjuvant and/or adjuvant therapy. Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology consensus definition, i.e. three consecutive increases in prostate-specific antigen (PSA) level after the nadir. The median (range) age, PSA level and follow-up were 71 (45-87) years, 8.5 (3.39-57.0) ng/mL and 22.0 (3-63) months, respectively. RESULTS: The overall biochemical disease-free rate was 75% (47 patients). The 3-year biochemical DFS rates for patients with a PSA level before HIFU of <10, 10.01-20 and >20 ng/mL were 82%, 62% and 20% (P < 0.001), respectively. The 3-year biochemical DFS rates for patients with a PSA nadir of <0.2, 0.21-1 and >1 ng/mL were 100%, 74% and 21% (P < 0.001), respectively. Final follow-up sextant biopsies showed that 55 (87%) of the patients were cancer-free. Multivariate analysis showed that the PSA nadir (P < 0.001) was a significant independent predictor of relapse. CONCLUSION: HIFU therapy appears to be a safe, effective and minimally invasive therapy for patients with localized prostate cancer, and the PSA nadir is a useful predictor of clinical outcome.

OBJECTIVE: To report on the long-term results of high-intensity focused ultrasound in the treatment of localized prostate cancer. METHODS: A total of 517 men with stage T1c-T3N0M0 prostate cancer treated with Sonablate devices (Focus Surgery, Indianapolis, IN, USA) between January 1999 and December 2007 were included in the study. Biochemical failure was defined according to the Phoenix definition (prostate-specific antigen nadir + 2 ng/mL). results: The median follow-up period for all patients was 24.0 months (range, 2 to 88). The biochemical disease-free rate (BDFR) in all patients at 5 years was 72%. The BDFR in patients with stage T1c, T2a, T2b, T2c and T3 groups at 5 years were 74%, 79%, 72%, 24% and 33%, respectively (P < 0.0001). BDFR in patients in the low, intermediate and high-risk groups at 5 years were 84%, 64% and 45%, respectively (P < 0.0001). The BDFR in patients treated with or without neoadjuvant hormonal therapy at 7 years were 73% and 53% (P < 0.0001), respectively. In multivariate analysis, pretreatment prostate-specific antigen levels (hazard ratio 1.060; P < 0.0001; 95% confidence interval 1.040-1.080), neoadjuvant hormonal therapy (hazard ratio 2.252; P < 0.0001; 95% confidence interval 1.530-3.315) and stage (P = 0.0189) were demonstrated to be statistically significant variables. Postoperative erectile dysfunction was noted in 33 out of 114 (28.9%) patients who were preoperatively potent. CONCLUSIONS: High-intensity focused ultrasound therapy appears to be minimally invasive, efficacious and safe for patients with localized prostate cancer, particularly those with low- and intermediate-risk cancer.

BACKGROUND: Asthma is a heterogeneous disease composed of various phenotypes. Periostin, a molecule inducible with interleukin (IL)-4 or IL-13 in bronchial epithelial cells, is a biomarker of "TH2-high" asthma. The objective of this study is to examine whether the serum periostin concentrations are correlated with the severity, specific phenotype(s), or comorbidity of asthma. METHODS: Serum concentrations of periostin were measured in 190 Japanese asthmatic patients and 11 healthy controls. The protocol was registered under UMIN 000002980 in the clinical trial registry. RESULTS: The serum concentrations of periostin were significantly higher (P = 0.014) in asthmatics [70.0 (54.0-93.5) ng/ml] than in healthy subjects [57.0 (39.0-63.0) ng/ml], though we found no correlation between serum periostin concentrations and treatment steps required to control asthma. To characterize "high-periostin" phenotype(s), the patients with asthma were divided among tertiles based on the serum concentrations of periostin. The high-periostin group was older at onset of asthma (P = 0.04), had a higher prevalence of aspirin intolerance (P = 0.04) or concomitant nasal disorders (P = 0.03-0.001), higher peripheral eosinophil counts (P < 0.001), and lower pulmonary function (P = 0.02-0.07). The serum concentrations of periostin were particularly high in asthmatic patients complicated by chronic rhinosinusitis with nasal polyps and olfactory dysfunction. In contrast, neither atopic status, control status of asthma, nor quality of life were related with the "high-periostin" phenotype. CONCLUSION: Elevated periostin concentrations in serum were correlated with a specific phenotype of eosinophilic asthma, late-onset and often complicated by obstructive pulmonary dysfunction and nasal disorders.

Primary Percutaneous Coronary Intervention (PCI) has significantly contributed to reducing the mortality of patients with ST-segment elevation myocardial infarction (STEMI) even in cardiogenic shock and is now the standard of care in most of Japanese institutions. The Task Force on Primary PCI of the Japanese Association of Cardiovascular Interventional and Therapeutics (CVIT) society proposed an expert consensus document for the management of acute myocardial infarction (AMI) focusing on procedural aspects of primary PCI in 2018. Updated guidelines for the management of AMI were published by the European Society of Cardiology (ESC) in 2017 and 2020. Major changes in the guidelines for STEMI patients included: (1) radial access and drug-eluting stents (DES) over bare-metal stents (BMS) were recommended as a Class I indication, (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. In 2020, updated guidelines for Non-ST-Elevation Myocardial Infarction (NSTEMI) patients, the followings were changed: (1) an early invasive strategy within 24 h is recommended in patients with NSTEMI as a Class I indication, (2) complete revascularization in NSTEMI patients without cardiogenic shock is considered as Class IIa recommendation, and (3) in patients with atrial fibrillation following a short period of triple antithrombotic therapy, dual antithrombotic therapy (e.g., DOAC and single oral antiplatelet agent preferably clopidogrel) is recommended, with discontinuation of the antiplatelet agent after 6 to 12 months. Furthermore, an aspirin-free strategy after PCI has been investigated in several trials those have started to show the safety and efficacy. The Task Force on Primary PCI of the CVIT group has now proposed the updated expert consensus document for the management of AMI focusing on procedural aspects of primary PCI in 2022 version.

BACKGROUND: For early gastric cancer located in the upper third of the stomach, we have adopted laparoscopic 1/2-proximal gastrectomy (PG) with two types of reconstruction: double tract reconstruction (L-DT) and jejunal interposition reconstruction with crimping of the jejunum on the anal side of the jejunogastrostomy with a knifeless linear stapler (L-JIP). METHODS: Functional outcomes were prospectively compared between these two types of reconstruction following laparoscopic PG. Resection and reconstruction were performed using L-DT (n = 10) and L-JIP (n = 10) alternately. Quality of life was evaluated through a questionnaire and endoscopic examination of the ten patients in each group, and functional evaluations were carried out in five patients of each group. RESULTS: The postoperative/preoperative body weight ratio was significantly higher in the L-JIP group than in the L-DT group. While the incidence of reflux esophagitis was 10% in both groups, the endoscope could reach the remnant stomach in all patients. In the L-DT group, the plasma acetaminophen concentration at 15 minutes and the insulin level at 30 minutes were markedly increased after oral administration, while the increases in the blood sugar level at 30 and 60 minutes were more gradual than in the L-JIP group. CONCLUSIONS: While L-JIP may be thought of as the ideal method for function-preserving gastrectomy, L-DT may be suitable for gastric cancer patients with impaired glucose tolerance. These results raise the possibility of individualized selection of reconstruction for gastric cancer patients with various kinds of preoperative complications.

BACKGROUND AND PURPOSE: [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc.This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine. METHODS: Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members. RESULTS: A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs. CONCLUSIONS: Based on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.

Satisfactory results have not yet been obtained in therapy for secondary prevention in ischemic stroke patients with antiphospholipid syndrome (APS). We therefore compared single antiplatelet therapy and a combination of antiplatelet and anticoagulation therapy for secondary prevention in ischemic stroke patients with APS.The subjects were 20 ischemic stroke patients with antiphospholipid antibody, 13 with primary antiphospholipid syndrome and 7 with SLE-related antiphospholipid syndrome. Diagnosis of APS was based on the 2006 Sydney criteria. Eligible patients were randomly assigned to either single antiplatelet therapy (aspirin 100 mg) or a combination of antiplatelet and anticoagulation therapy (target INR: 2.0-3.0; mean 2.4+/-0.3) for the secondary prevention of stroke according to a double-blind protocol. There was no significant difference between the two groups in age, gender, NIH Stroke Scale on admission, mRS at discharge, or rate of hypertension, diabetes mellitus, hyperlipidemia, or cardiac disease. We obtained Kaplan-Meier survival curves for each treatment. The primary outcome was the occurrence of stroke. The mean follow-up time was 3.9+/-2.0 years. The cumulative incidence of stroke in patients with single antiplatelet treatment was statistically significantly higher than that in patients receiving the combination of antiplatelet and anticoagulation therapy (log-rank test, p-value=0.026). The incidence of hemorrhagic complications was similar in the two groups. The recent APASS study did not show any difference in effectiveness for secondary prevention between single antiplatelet (aspirin) and single anticoagulant (warfarin) therapy. Our results indicate that combination therapy may be more effective in APS-related ischemic stroke.

Oral conditions are relatively common in patients with inflammatory bowel disease (IBD). However, the contribution of oral maladies to gut inflammation remains unexplored. Here, we investigated the effect of periodontitis on disease phenotypes of patients with IBD. In all, 60 patients with IBD (42 with ulcerative colitis [UC] and 18 with Crohn's disease [CD]) and 45 healthy controls (HCs) without IBD were recruited for this clinical investigation. The effects of incipient periodontitis on the oral and gut microbiome as well as IBD characteristics were examined. In addition, patients were prospectively monitored for up to 12 months after enrollment. We found that, in both patients with UC and those with CD, the gut microbiome was significantly more similar to the oral microbiome than in HCs, suggesting that ectopic gut colonization by oral bacteria is increased in patients with IBD. Incipient periodontitis did not further enhance gut colonization by oral bacteria. The presence of incipient periodontitis did not significantly affect the clinical outcomes of patients with UC and CD. However, the short CD activity index increased in patients with CD with incipient periodontitis but declined or was unchanged during the study period in patients without periodontitis. Thus, early periodontitis may associate with worse clinically symptoms in some patients with CD.

Importance: Patients with chronic kidney disease have impaired vitamin D activation and elevated cardiovascular risk. Observational studies in patients treated with hemodialysis showed that the use of active vitamin D sterols was associated with lower risk of all-cause mortality, regardless of parathyroid hormone levels. Objective: To determine whether vitamin D receptor activators reduce cardiovascular events and mortality in patients without secondary hyperparathyroidism undergoing hemodialysis. Design, Setting, and Participants: Randomized, open-label, blinded end point multicenter study of 1289 patients in 207 dialysis centers in Japan. The study included 976 patients receiving maintenance hemodialysis with serum intact parathyroid hormone levels less than or equal to 180 pg/mL. The first and last participants were enrolled on August 18, 2008, and January 26, 2011, respectively. The final date of follow-up was April 4, 2015. Interventions: Treatment with 0.5 μg of oral alfacalcidol per day (intervention group; n = 495) vs treatment without vitamin D receptor activators (control group; n = 481). Main Outcomes and Measures: The primary outcome was a composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization during 48 months of follow-up. The secondary outcome was all-cause death. Results: Among 976 patients who were randomized from 108 dialysis centers, 964 patients were included in the intention-to-treat analysis (median age, 65 years; 386 women [40.0%]), and 944 (97.9%) completed the trial. During follow-up (median, 4.0 years), the primary composite outcome of cardiovascular events occurred in 103 of 488 patients (21.1%) in the intervention group and 85 of 476 patients (17.9%) in the control group (absolute difference, 3.25% [95% CI, -1.75% to 8.24%]; hazard ratio, 1.25 [95% CI, 0.94-1.67]; P = .13). There was no significant difference in the secondary outcome of all-cause mortality between the groups (18.2% vs 16.8%, respectively; hazard ratio, 1.12 [95% CI, 0.83-1.52]; P = .46). Of the 488 participants in the intervention group, 199 (40.8%) experienced serious adverse events that were classified as cardiovascular, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced malignancy-related serious adverse events. Of 476 participants in the control group, 191 (40.1%) experienced cardiovascular-related serious adverse events, 63 (13.2%) experienced infection-related serious adverse events, and 21 (4.4%) experienced malignancy-related adverse events. Conclusions and Relevance: Among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select cardiovascular events. These findings do not support the use of vitamin D receptor activators for patients such as these. Trial Registration: UMIN-CTR Identifier: UMIN000001194.

PURPOSE: We evaluated the association between long-term clinical outcomes and morbidity with high intensity focused ultrasound. MATERIALS AND METHODS: We included patients with stage T1c-T3N0M0 prostate cancer who were treated with Sonablate® (SB) devices during 1999 to 2012 and followed for more than 2 years. Risk stratification and complication rates were compared among the treatment groups (ie SB200/500 group, SB500 version 4 group and SB500 tissue change monitor group). Primary study outcomes included overall, cancer specific and biochemical disease-free survival rates determined using Kaplan-Meier analysis (Phoenix definition). Secondary outcomes included predictors of biochemical disease-free survival using Cox models. RESULTS: A total of 918 patients were included in the study. Median followup in the SB200/500, SB500 version 4 and the SB500 tissue change monitor groups was 108, 83 and 47 months, respectively. The 10-year overall and cancer specific survival rates were 89.6% and 97.4%, respectively. The 5-year biochemical disease-free survival rate in the SB200/500, SB500 version 4 and SB500 tissue change monitor group was 48.3%, 62.3% and 82.0%, respectively (p < 0.0001). The overall negative biopsy rate was 87.3%. On multivariate analysis pretreatment prostate specific antigen, Gleason score, stage, neoadjuvant androgen deprivation therapy and high intensity focused ultrasound devices were significant predictors of biochemical disease-free survival. Urethral stricture, epididymitis, urinary incontinence and rectourethral fistula were observed in 19.7%, 6.2%, 2.3% and 0.1% of cases, respectively. CONCLUSIONS: Long-term followup of patients with high intensity focused ultrasound demonstrated improved clinical outcomes due to technical, imaging and technological advancements.