Chiba Hokusou Hospital

The objective of this study was to systematically determine the diagnostic accuracy of bedside tests for predicting difficult intubation in patients with no airway pathology. Thirty-five studies (50,760 patients) were selected from electronic databases. The overall incidence of difficult intubation was 5.8% (95% confidence interval, 4.5-7.5%). Screening tests included the Mallampati oropharyngeal classification, thyromental distance, sternomental distance, mouth opening, and Wilson risk score. Each test yielded poor to moderate sensitivity (20-62%) and moderate to fair specificity (82-97%). The most useful bedside test for prediction was found to be a combination of the Mallampati classification and thyromental distance (positive likelihood ratio, 9.9; 95% confidence interval, 3.1-31.9). Currently available screening tests for difficult intubation have only poor to moderate discriminative power when used alone. Combinations of tests add some incremental diagnostic value in comparison to the value of each test alone. The clinical value of bedside screening tests for predicting difficult intubation remains limited.

BACKGROUND: Protection from lethal ventricular arrhythmias leading to sudden cardiac death (SCD) is a crucial challenge after acute myocardial infarction (AMI). Cardiac sympathetic and parasympathetic activity can be noninvasively assessed using heart rate variability (HRV) and heart rate turbulence (HRT). The EMBODY trial was designed to determine whether the Sodium-glucose cotransporter 2 (SGLT2) inhibitor improves cardiac nerve activity. METHODS: This prospective, multicenter, randomized, double-blind, placebo-controlled trial included patients with AMI and type 2 diabetes mellitus (T2DM) in Japan; 105 patients were randomized (1:1) to receive once-daily 10-mg empagliflozin or placebo. The primary endpoints were changes in HRV, e.g., the standard deviation of all 5-min mean normal RR intervals (SDANN) and the low-frequency-to-high-frequency (LF/HF) ratio from baseline to 24 weeks. Secondary endpoints were changes in other sudden cardiac death (SCD) surrogate markers such as HRT. RESULTS: Overall, 96 patients were included (46, empagliflozin group; 50, placebo group). The changes in SDANN were + 11.6 and + 9.1 ms in the empagliflozin (P = 0.02) and placebo groups (P = 0.06), respectively. Change in LF/HF ratio was - 0.57 and - 0.17 in the empagliflozin (P = 0.01) and placebo groups (P = 0.43), respectively. Significant improvement was noted in HRT only in the empagliflozin group (P = 0.01). Whereas intergroup comparison on HRV and HRT showed no significant difference between the empagliflozin and placebo groups. Compared with the placebo group, the empagliflozin group showed significant decreases in body weight, systolic blood pressure, and uric acid. In the empagliflozin group, no adverse events were observed. CONCLUSIONS: This is the first randomized clinical data to evaluate the effect of empagliflozin on cardiac sympathetic and parasympathetic activity in patients with T2DM and AMI. Early SGLT2 inhibitor administration in AMI patients with T2DM might be effective in improving cardiac nerve activity without any adverse events. TRIAL REGISTRATION: The EMBODY trial was registered by the UMIN in November 2017 (ID: 000030158). UMIN000030158; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034442 .

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

INTRODUCTION: To test the hypothesis that the administration of antithrombin concentrate improves disseminated intravascular coagulation (DIC), resulting in recovery from DIC and better outcomes in patients with sepsis, we conducted a prospective, randomized controlled multicenter trial at 13 critical care centers in tertiary care hospitals. METHODS: We enrolled 60 DIC patients with sepsis and antithrombin levels of 50 to 80% in this study. The participating patients were randomly assigned to an antithrombin arm receiving antithrombin at a dose of 30 IU/kg per day for three days or a control arm treated with no intervention. The primary efficacy end point was recovery from DIC on day 3. The analysis was conducted with an intention-to-treat approach. DIC was diagnosed according to the Japanese Association for Acute Medicine (JAAM) scoring system. The systemic inflammatory response syndrome (SIRS) score, platelet count and global markers of coagulation and fibrinolysis were measured on day 0 and day 3. RESULTS: Antithrombin treatment resulted in significantly decreased DIC scores and better recovery rates from DIC compared with those observed in the control group on day 3. The incidence of minor bleeding complications did not increase, and no major bleeding related to antithrombin treatment was observed. The platelet count significantly increased; however, antithrombin did not influence the sequential organ failure assessment (SOFA) score or markers of coagulation and fibrinolysis on day 3. CONCLUSIONS: Moderate doses of antithrombin improve DIC scores, thereby increasing the recovery rate from DIC without any risk of bleeding in DIC patients with sepsis. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000000882.

BACKGROUND: Ventricular arrhythmias are one of the main causes of sudden death in cardiac sarcoidosis (CS). Little is known about the efficacy of corticosteroid therapy for ventricular arrhythmias in CS. METHODS: Thirty-one CS patients presenting premature ventricular contractions (PVCs, ≥300/day) were investigated. Fourteen patients had nonsustained ventricular tachycardia (NSVT). All of patients were treated with corticosteroid, and the initial dosage is 30 mg/day of prednisone, which was tapered over a period of 6 months to a maintenance dosage of 10 mg/day. Twenty-four hour Holter monitoring, signal averaged electrocardiography (SAECG), echocardiography, gallium-67 scintigraphy, serum angiotensin converting enzyme (ACE) and plasma B-type natriuretic peptide (BNP) concentrations were assessed before and after corticosteroid therapy. RESULTS: As a whole, there were no significant differences in the number of PVCs and in the prevalence of NSVT before and after steroid therapy. However, the less advanced LV dysfunction patients (EF ≥ 35%, n = 17) showed significant reduction in the number of PVCs (from 1820 ± 2969 to 742 ± 1425, P = 0.048) and in the prevalence of NSVT (from 41 to 6%, p = 0.039). Late potentials on SAECG were abolished in 3 patients. The less advanced LV dysfunction group showed a significantly higher prevalence of gallium-67 uptake compared with the advanced LV dysfunction group (EF < 35 %, n = 14). In the advanced LV dysfunction patients, there were no significant differences in these parameters. CONCLUSIONS: Corticosteroid therapy may be effective for ventricular arrhythmias in the early stage, but less effective in the late stage.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by T helper 2 cell (Th2)-shifted abnormal immunity, skin barrier impairment, and pruritus. The prevalence of AD in childhood is slightly higher in boys than in girls; after puberty, the sexual difference is reversed. The female preponderance in all generations exists in intrinsic AD with enhanced Th1 activity and nickel allergy, lacking increased serum IgE or filaggrin mutation. AD is often deteriorated before menstruation. We review the effects of sex hormones on immune responses and skin permeability barrier and propose possible hypotheses for the above phenomena. After puberty, the immune responses of patients are remarkably influenced by sex hormones. Estrogen and progesterone enhance the activities of Th2/regulatory T cell (Treg) but suppress Th1/Th17. Androgens suppress Th1/Th2/Th17 and induce Treg. The skin permeability barrier is fortified by estrogen but is impaired by progesterone and androgens. Dehydroepiandrosterone suppresses Th2 but enhances Th1. The amount of steroid sulfatase converting dehydroepiandrosterone sulfate to dehydroepiandrosterone is higher in women than in men, and thus, women might be more susceptible to the influence of dehydroepiandrosterone. The balance of modulatory effects of sex hormones on immune responses and skin barrier might regulate the course of AD.

BACKGROUND: The diagnosis of myelodysplastic syndromes is not always straightforward when patients lack specific diagnostic markers, such as blast excess, karyotype abnormality, and ringed sideroblasts. DESIGN AND METHODS: We designed a flow cytometry protocol applicable in many laboratories and verified its diagnostic utility in patients without those diagnostic markers. The cardinal parameters, analyzable from one cell aliquot, were myeloblasts (%), B-cell progenitors (%), myeloblast CD45 expression, and channel number of side scatter where the maximum number of granulocytes occurs. The adjunctive parameters were CD11b, CD15, and CD56 expression (%) on myeloblasts. Marrow samples from 106 control patients with cytopenia and 134 low-grade myelodysplastic syndromes patients, including 81 lacking both ringed sideroblasts and cytogenetic aberrations, were prospectively analyzed in Japan and Italy. RESULTS: Data outside the predetermined reference range in 2 or more parameters (multiple abnormalities) were common in myelodysplastic syndromes patients. In those lacking ringed sideroblasts and cytogenetic aberrations, multiple abnormalities were observed in 8/26 Japanese (30.8%) and 37/55 Italians (67.3%) when the cardinal parameters alone were considered, and in 17/26 Japanese (65.4%) and 42/47 Italians (89.4%) when all parameters were taken into account. Multiple abnormalities were rare in controls. When data from all parameters were used, the diagnostic sensitivities were 65% and 89%, specificities were 98% and 90%, and likelihood ratios were 28.1 and 8.5 for the Japanese and Italian cohorts, respectively. CONCLUSIONS: This protocol can be used in the diagnostic work-up of low-grade myelodysplastic syndromes patients who lack specific diagnostic markers, although further improvement in diagnostic power is desirable.

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.

PURPOSE The International Union Against Cancer highlighted tumor budding as a tumor-related prognostic factor. International assessment criteria for tumor budding were recently defined by the 2016 International Tumor Budding Consensus Conference (ITBCC2016). This study aimed to clarify the prognostic and predictive values of tumor budding in a randomized controlled trial evaluating the superiority of adjuvant chemotherapy with oral tegafur-uracil over surgery alone for stage II colon cancer (SACURA trial; ClinicalTrials.gov identifier: NCT00392899 ). PATIENTS AND METHODS Between 2006 and 2010, we enrolled 991 patients from 123 institutions with stage II colon cancer. Tumor budding was diagnosed by central review on the basis of the criteria adopted in the ITBCC2016. We prospectively recorded all clinical and pathologic data, including the budding grade, and performed prognostic analyses after 5 years of completing the patients’ registration. RESULTS Of 991 tumors, 376, 331, and 284 were classified as BD1, BD2, and BD3, respectively; the 5-year relapse-free survival (RFS) rate was 90.9%, 85.1%, and 74.4%, respectively ( P &lt; .001), and ranged widely in T4 tumors (86.6% to 53.3%). The budding grade significantly correlated with recurrence in the liver, lungs, lymph nodes, and peritoneum ( P &lt; .001 to .01). Multivariable analysis revealed that budding and T stage exerted an independent impact on RFS, and on the basis of the Harrell concordance index, these two factors substantially contributed to the improvement of the Cox model for predicting RFS. Both the BD2 and BD3 groups demonstrated greater improvement in the 5-year recurrence rate in the adjuvant chemotherapy group than the surgery-alone group by approximately 5%, but the difference was statistically nonsignificant. CONCLUSION Tumor budding grade on the basis of the ITBCC2016 criteria should be routinely evaluated in pathologic practice and could improve the benefit of adjuvant chemotherapy for stage II colon cancer.

OBJECTIVE: The objective of this study was to investigate the mapping of sigma1 receptors in Parkinson's disease (PD) using [11C]SA4503 and positron emission tomography (PET), and to assess whether sigma1 receptors are involved in the damaged dopaminergic system in PD patients. MATERIALS AND METHODS: We studied seven normal volunteers and six PD patients. The low density of dopamine transporters and the normal or high density of dopamine receptors were confirmed in the putamen of all patients using [11C]CFT and [11C]RAC PET. A dynamic series of PET data acquisition was performed with arterial blood sampling. We computed the binding potential (BP) of [11C]SA4503. RESULTS: In PD patients, the BP was significantly lower on the more affected than the less affected side of the anterior putamen, although there was no significant difference with respect to the BP between patients and controls. CONCLUSIONS: Release of dopamine is reduced asymmetrically in the putamen of early PD. [11C]SA4503 PET is an indicator of presynaptic dopaminergic damage in PD.

Psoriasis is a chronic inflammatory skin disease characterized by accelerated tumor necrosis factor-α/interleukin-23/interleukin-17 axis, hyperproliferation and abnormal differentiation of epidermal keratinocytes. Psoriasis patients are frequently associated with obesity, diabetes, dyslipidemia, cardiovascular diseases, or inflammatory bowel diseases. Psoriasis patients often show unbalanced dietary habits such as higher intake of fat and lower intake of fish or dietary fibers, compared to controls. Such dietary habits might be related to the incidence and severity of psoriasis. Nutrition influences the development and progress of psoriasis and its comorbidities. Saturated fatty acids, simple sugars, red meat, or alcohol exacerbate psoriasis via the activation of nucleotide-binding domain, leucine-rich repeats containing family, pyrin domain-containing-3 inflammasome, tumor necrosis factor-α/interleukin-23/interleukin-17 pathway, reactive oxygen species, prostanoids/leukotrienes, gut dysbiosis or suppression of regulatory T cells, while n-3 polyunsaturated fatty acids, vitamin D, vitamin B12, short chain fatty acids, selenium, genistein, dietary fibers or probiotics ameliorate psoriasis via the suppression of inflammatory pathways above or induction of regulatory T cells. Psoriasis patients are associated with dysbiosis of gut microbiota and the deficiency of vitamin D or selenium. We herein present the update information regarding the stimulatory or regulatory effects of nutrients or food on psoriasis and the possible alleviation of psoriasis by nutritional strategies.

INTRODUCTION: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria. METHODS: The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO2/FiO2 ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy. RESULTS: Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P < 0.01). PVPI was higher in ALI/ARDS patients than in cardiogenic edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P < 0.01). In ALI/ARDS patients, EVLWI increased with increasing pulmonary vascular permeability (r = 0.729, P < 0.01) and was weakly correlated with intrathoracic blood volume (r = 0.236, P < 0.01). EVLWI was weakly correlated with the PaO2/FiO2 ratio in the ALI/ARDS and cardiogenic edema patients. A PVPI value of 2.6 to 2.85 provided a definitive diagnosis of ALI/ARDS (specificity, 0.90 to 0.95), and a value < 1.7 ruled out an ALI/ARDS diagnosis (specificity, 0.95). CONCLUSION: PVPI may be a useful quantitative diagnostic tool for ARDS in patients with hypoxemic respiratory failure and radiographic infiltrates. TRIAL REGISTRATION: UMIN-CTR ID UMIN000003627.

BACKGROUND: Carperitide is used to treat acute decompensated heart failure (ADHF), but its effects on long-term prognosis have not been studied. METHODS AND RESULTS: A multicenter randomized controlled study of 49 patients with ADHF was performed to clarify the drug's effects on long-term prognosis. Low-dose carperitide (0.01-0.05 microg x kg(-1 ) x min(-1)) was infused for 72 h as the initial treatment (n=26), whereas in the control group (n=23), standard medical treatment other than carperitide was given without limitation. Anti-aldosterone drugs were prohibited in both groups. During carperitide infusion, significant increases of the atrial natriuretic peptide and cyclic GMP levels and a significant decrease in the heart-type fatty acid-binding protein/serum creatinine ratio were observed, suggesting inhibition of myocyte cell membrane damage. On the other hand, no significant differences in the plasma brain natriuretic peptide, troponin T, and creatinine levels were noted in either group. During 18-month follow-up, significant reductions of death and rehospitalization occurred in the carperitide vs control group (11.5% vs 34.8%; p=0.0359). Cox regression analysis revealed that randomization to carperitide (p=0.020), pretreatment systolic blood pressure >or=140 mmHg (p=0.043), and beta-blocker therapy (p=0.016) were independent predictors for freedom from cardiac events. CONCLUSIONS: Acute-phase low-dose carperitide infusion improved the long-term prognosis of patients with ADHF.

PURPOSE: To report the results after 4 years of follow-up in a previously presented first case of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) sheet autologous transplantation using multimodal imaging. DESIGN: Follow-up of a single case. PARTICIPANT: A patient with exudative age-related macular degeneration and polypoidal choroidal vasculopathy. METHODS: Transplantation of an autologous iPSC-derived RPE cell sheet after removal of choroidal neovascularization (CNV) in September 2014. MAIN OUTCOME MEASURES: The function of the graft was assessed 4 years after surgery by color fundus photography, spectral-domain (SD) OCT, fluorescein angiography, indocyanine green angiography, and an adaptive optics (AO) retinal camera. RESULTS: At the 4-year follow-up, the transplanted autologous iPSC-derived RPE sheet had survived beneath the retina with slight expansion of the pigmented area and no adverse events. The outer nuclear layer above and adjacent to the graft showed acceptable thickness and an organized structure. Fluorescein angiography and SD OCT suggested the presence of vessel-like structures confined to the grafted area associated with the remaining trunk vessel of preoperative polypoidal choroidal vasculopathy but with no exudative changes. Visual acuity has been stable with no additional injections of anti-vascular endothelial growth factor agent. The choroidal volume at the graft site is relatively preserved when compared with the volume outside this site without RPE after removal of the CNV. Indocyanine green angiography revealed a preserved choriocapillaris around the iPSC-derived RPE sheet. Dark cell-like structures with a predominantly hexagonal arrangement were observed by AO imaging in an area located near the margin of the graft sheet. The average intercell distance was found to be stable over time. CONCLUSIONS: Thus far, the grafted iPSC-derived RPE sheet has survived for 4 years and seems to support photoreceptors and choroidal vessels. The morphologic characteristics of the RPE are observed at the transplant site.

STUDY DESIGN: The histochemical changes in the multifidus muscle in 29 patients with L4-L5 lumbar intervertebral disc herniation were studied. OBJECTIVES: To clarify how nerve root impairment affects the histochemical properties of the lumbar multifidus muscle in patients with lumbar intervertebral disk herniation. SUMMARY OF BACKGROUND DATA: There have been several studies on histochemical changes in lumbar muscles in patients with nerve root impairment, but the findings concerning changes in muscle fiber sizes vary among investigators. METHODS: Biopsy specimens were obtained intraoperatively from the L4 and L5 bands of the multifidus muscle on the affected and nonaffected sides. The specimens were stained with ATPase to evaluate the size of the fibers and structural changes. RESULTS: In the L5 muscle band, the mean sizes of Type 1 and Type 2 fibers on the affected side were significantly smaller than those on the nonaffected side (Type 1: P < 0.01, Type 2: P < 0.001). The decrease in size was 6.4% for Type 1 and 9.8% for Type 2. Increased percentages of Type 1 fibers and a high incidence of small angular fibers and fiber type grouping were also shown on the affected side. In contrast, in the L4 muscle band, no side-to-side differences in the histologic findings were observed. There was no significant level-to-level difference in the mean size of Type 1 or Type 2 fibers on either the affected or the nonaffected side. CONCLUSIONS: These results suggest that nerve root impairment leads to atrophy of Type 1 and Type 2 fibers, with structural changes in the multifidus muscle only at the involved level.

Adenosine A(2A) receptors (A2ARs) are thought to interact negatively with the dopamine D(2) receptor (D2R), so selective A2AR antagonists have attracted attention as novel treatments for Parkinson's disease (PD). However, no information about the receptor in living patients with PD is available. The purpose of this study was to investigate the relationship between A2ARs and the dopaminergic system in the striata of drug-naïve PD patients and PD patients with dyskinesia, and alteration of these receptors after antiparkinsonian therapy. We measured binding ability of striatal A2ARs using positron emission tomography (PET) with [7-methyl-(11)C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([(11)C]TMSX) in nine drug-naïve patients with PD, seven PD patients with mild dyskinesia and six elderly control subjects using PET. The patients and eight normal control subjects were also examined for binding ability of dopamine transporters and D2Rs. Seven of the drug-naïve patients underwent a second series of PET scans following therapy. We found that the distribution volume ratio of A2ARs in the putamen were larger in the dyskinesic patients than in the control subjects (p<0.05, Tukey-Kramer post hoc test). In the drug-naïve patients, the binding ability of the A2ARs in the putamen, but not in the head of caudate nucleus, was significantly lower on the more affected side than on the less affected side (p<0.05, paired t-test). In addition, the A2ARs were significantly increased after antiparkinsonian therapy in the bilateral putamen of the drug-naïve patients (p<0.05, paired t-test) but not in the bilateral head of caudate nucleus. Our study demonstrated that the A2ARs in the putamen were increased in the PD patients with dyskinesia, and also suggest that the A2ARs in the putamen compensate for the asymmetrical decrease of dopamine in drug-naïve PD patients and that antiparkinsonian therapy increases the A2ARs in the putamen. The A2ARs may play an important role in regulation of parkinsonism in PD.

BACKGROUND: Elevated troponin T levels in non-ST-elevation acute coronary syndromes (NSTE-ACS) have been shown to predict an adverse outcome. Furthermore, it has been reported that troponin T could help improve the effectiveness of such new antithrombotic drugs as platelet GPIIb/IIIa antagonists and low-molecular-weight heparins. We hypothesized that such elevated troponin T levels in NSTE-ACS indicate the presence of thrombus at culprit lesions, and this hypothesis was verified through the use of coronary angioscopy. METHODS AND RESULTS: We studied 57 consecutive patients with NSTE-ACS who underwent preinterventional angioscopy. Before catheterization, we obtained blood samples to determine troponin positivity, and the patients were then classified as either troponin-positive or troponin-negative groups (diagnostic threshold, 0.1 ng/mL). Using angioscopy at the culprit lesions, we examined the presence of coronary thrombus, yellow plaque, and complex plaque. Moreover, we compared the preinterventional angiographic parameters (thrombus and complexity of the culprit lesion, and TIMI flow) between the two groups. Twenty-two patients were troponin-positive and 35 patients were troponin-negative. Univariate analyses indicated that the TIMI flow and the incidence of coronary thrombus detected with angioscopy correlate with the elevated troponin T levels. A multivariate logistic regression analysis showed the presence of coronary thrombus detected with angioscopy to be the only independent factor associated with elevated troponin T levels in patients with NSTE-ACS (odds ratio, 22.1; 95% CI, 2.59 to 188.42; P=0.0046). CONCLUSIONS: Using angioscopy, the elevated troponin T levels in NSTE-ACS were confirmed to be strongly associated with the presence of coronary thrombus.

BACKGROUND: A rapid heart rate (HR) during atrial fibrillation (AF) and atrial flutter (AFL) in left ventricular (LV) dysfunction often impairs cardiac performance. The J-Land study was conducted to compare the efficacy and safety of landiolol, an ultra-short-acting β-blocker, with those of digoxin for swift control of tachycardia in AF/AFL in patients with LV dysfunction. METHODS AND RESULTS: The 200 patients with AF/AFL, HR ≥120beats/min, and LV ejection fraction 25-50% were randomized to receive either landiolol (n=93) or digoxin (n=107). Successful HR control was defined as ≥20% reduction in HR together with HR <110beats/min at 2h after starting intravenous administration of landiolol or digoxin. The dose of landiolol was adjusted in the range of 1-10µg·kg(-1)·min(-1) according to the patient's condition. The mean HR at baseline was 138.2±15.7 and 138.0±15.0beats/min in the landiolol and digoxin groups, respectively. Successful HR control was achieved in 48.0% of patients treated with landiolol and in 13.9% of patients treated with digoxin (P<0.0001). Serious adverse events were reported in 2 and 3 patients in each group, respectively. CONCLUSIONS: Landiolol was more effective for controlling rapid HR than digoxin in AF/AFL patients with LV dysfunction, and could be considered as a therapeutic option in this clinical setting.

Several studies have reported on the use of antibodies to monoclonal carcinoembryonic antigen (CEA) and vimentin (VIM) to distinguish between adenocarcinomas of endometrial (EM) and endocervical (EC) origin, with variably enthusiastic results. It is still unclear whether site of origin or pathway of differentiation (endometrioid [em] versus mucinous [m]) is more important in predicting immunohistochemical differences. In the present study, paraffin blocks from adenocarcinomas of known origin were retrieved and immunostained with monoclonal antibodies to VIM and CEA, as well as cytokeratins (CK) 4, 18, and 20, estrogen receptor (ER), and progesterone receptor (PR). Positivity was scored on a scale from 0 to 12, with emphasis on the pattern of differentiation (tumors with mixed patterns received separate scores for the em and m foci). Mean CEA scores for emEM (n = 27), mEM (17), mEC (10), and emEC (6) were 0.4, 0.9, 5.1, and 1.2, respectively. VIM scores were 6.9, 1.3, 0, 4.4; ER, 5.7, 4.2, 0, 1.6; PR, 7.6, 2.8, 0.1, 6.0; CK4, 9.2, 4.4, 8.5, 10.6; CK18, 6.4, 3.4, 5.5, 8.4; CK20, 0.7, 0, 0.5, 0.4. Both site and differentiation influenced these results, with the latter more important for VIM and PR, the former for ER, both for CEA (only mEC was frequently strongly positive), and neither for the CKs studied. No one stain or combination reliably distinguished endometrial from endocervical origin. The only immunostaining pattern that might identify a site of origin with more accuracy than hematoxylin & eosin evaluation alone is the combination of high VIM and ER scores in an endometrioid carcinoma, suggesting with about 95% accuracy in this series an endometrial origin of the tumor.

BACKGROUND: Green tea, a popular beverage in Japan, contains many polyphenolic antioxidants, which might prevent atherosclerosis. This study was designed to determine whether the consumption of green tea is proportionately associated with a decreased incidence of coronary artery disease (CAD) and the cardiovascular and cerebrovascular prognosis. METHODS AND RESULTS: The study group comprised 203 patients who underwent coronary angiography (109 patients with significant coronary stenosis and 94 patients without). Predictors for CAD were analyzed and the patients' cardiovascular and cerebrovascular events were followed. Green tea consumption was significantly higher in patients without CAD than in those with CAD (5.9+/-0.5 vs 3.5+/-0.3 cups/day; p<0.001). An inverse relationship between the intake of green tea and the incidence of CAD was observed (p<0.001). The green tea intake per day was an independent predictor for CAD based on a multivariate logistic regression analysis (odds ratio: 0.84 and 95% confidence interval: 0.76-0.91). In contrast, the green tea intake was not a predictor of cardiovascular and cerebrovascular events based on the Cox proportional hazard model. CONCLUSIONS: Green tea consumption was associated with a lower incidence of CAD in the present study population in Japan. Therefore, the more green tea patients consume, the less likely they are to have CAD.