Impact of the Aortomitral Positional Anatomy on Atrioventricular Conduction Disorder Following Mitral Valve Surgery.

BACKGROUND: Variations in the aortomitral positional anatomy, including aortic root rotation appear to be related to variations in the location of the conduction system, including the bundle of His. However, little is known about their clinical significance. METHODS AND RESULTS: This study included 147 patients with normal ECGs who underwent mitral valve surgery. The aortomitral anatomy was classified using preoperative 3-dimensional transesophageal echocardiography, and postoperative conduction disorders, including atrioventricular block and bundle branch block, were analyzed. Variations classified as aortomitral appearance were designated as having a center appearance (85.7%, n=126/147) or lateral appearance (14.3%, n=21/147) on the basis of whether the aortic root was located at the center or was shifted to the left fibrous trigone side. Subsequently, those with a center appearance, aortic root rotation was classified as having a center rotation (83.3% [n=105/126]), in which the commissure of the left and noncoronary aortic leaflet was located at the center, lateral rotation (14.3% [n=18/126]), rotated to the left trigone side, or medial rotation (2.4% [n=3/126]), rotated to the right. The incidence of 3-month persistent new-onset conduction disorder was higher in the lateral appearance than the center appearance group (21.1% versus 5.0%; P=0.031) and higher in the lateral rotation than in the center or medial rotation groups (29.4% versus 1.0% versus 0.0%, respectively; P<0.001). CONCLUSIONS: Aortomitral variations can be classified using 3-dimensional transesophageal echocardiography. Lateral appearance and lateral rotation are risk factors for conduction disorders in mitral valve surgery.

The foremost and greatest barrier to end-stage heart failure treatment: the impact of caregiver shortage.

We examined the number of patients abandoning cardiac replacement therapy due to the inability to secure a designated caregiver. At Osaka University Hospital Heart Center, when we receive a consultation for a patient with severe heart failure from another hospital, a heart failure team makes a visit to the referring hospital as soon as possible. We retrospectively analyzed this hospital-visit database. We received 199 severe heart failure consultations from 2016-2023. Issues identified during hospital visits included age ≥ 65 years (8%), inability to confirm the patient's intention (8.5%), and explicit refusal of therapy (2.5%). Medical problems included multiple organ failure (18.1%), obesity (13.1%), diabetes (9.5%), malignancy (5.5%), chronic dialysis (1.0%), and other systemic diseases (12.6%). Adherence problems included poor medication compliance (3.5%), history of heavy drinking (2.5%), and smoking (2.0%). Social problems included inadequate family support in 16.1% of patients. Of the 199 patients, 95 (48.0%) proceeded to a heart transplant and LVAD indication review meeting at Osaka University Hospital. The remaining 104 patients (52.0%) did not proceed to the meeting. Reasons included improvement of heart failure with conservative treatment in 37 cases (35.6%), death before discussion in 21 cases (20.2%), medical contraindications in 18 cases (18.3%), lack of caregivers in 18 cases (18.3%; 9.5% of 199 cases), and patient refusal in 5 cases (4.8%). Approximately 10% of patients consulted at Osaka University Hospital Heart Center for severe heart failure abandoned cardiac replacement therapy due to the lack of caregivers.

A risk model of mortality rate in dialysis patients following transcatheter aortic valve replacement.

BACKGROUND: Dialysis patients undergoing transcatheter aortic valve replacement (TAVR) generally have poor prognosis compared with non-dialysis patients. Furthermore, there are few reliable risk models in this clinical setting. Therefore, we aimed to establish a risk model in dialysis patients undergoing TAVR that would be informative for their prognosis and the decision-making process of TAVR. METHODS: A total 118 dialysis patients (full cohort) with severe aortic stenosis underwent TAVR in our institute between 2012 and 2022. The patients of the full cohort were randomly assigned to two groups in a 2:1 ratio to form derivation and validation cohorts. Risk factors contributing to deaths were analyzed from the preoperative variables and a risk model was established from Cox proportional hazard model. RESULTS: There were 69 deaths following TAVR derived from infectious disease (43.5 %), cardiovascular-related disease (11.6 %), cerebral stroke or hemorrhage (2.9 %), cancer (1.4 %), unknown origin (18.8 %), and others (21.7 %) during the observational period (811 ±â€¯719 days). The cumulative overall survival rates using the Kaplan-Meier method at 1 year, 3 years, and 5 years in the full cohort were 82.8 %, 41.9 %, and 24.2 %, respectively. An optimal risk model composed of five contributors: peripheral vascular disease, serum albumin, left ventricular ejection fraction < 40 %, operative age, and hemoglobin level, was established. The estimated C index for the developed models were 0.748 (95 % CI: 0.672-0.824) in derivation cohort and 0.705 (95 % CI: 0.578-0.832) in validation cohort. The prediction model showed good calibration [intraclass correlation coefficient = 0.937 (95%CI: 0.806-0.981)] between actual and predicted survival. CONCLUSIONS: The risk model was a good indicator to estimate the prognosis in dialysis patients undergoing TAVR.

Idiopathic basal ganglia calcification presenting with obsessive-compulsive symptoms: A case report.

Background: Idiopathic basal ganglia calcification (IBGC), also known as Farh's disease, is a rare neurodegenerative disorder characterized by calcification of the basal ganglia and other brain regions. This disease usually occurs in middle-aged patients and presents with various neurological and psychiatric symptoms. The exact prevalence is unknown; however, population genomic data analysis suggests a prevalence of at least 4.5/10,000 to 3.3/1000, indicating that the disease is more common than previously thought and remains underdiagnosed. Case Presentation: We report the case of a middle-aged Japanese man who attempted suicide twice because of obsessive-compulsive ideation caused by trivial triggers. The patient's psychiatric symptoms resolved relatively quickly after hospitalization, and imaging and genetic testing led to a diagnosis of IBGC. Conclusion: This case report illustrates the importance of including IBGC in the differential diagnosis of psychiatric symptoms that initially develop in middle-aged patients.

Obsessive-compulsive disorder after traumatic injury to the right frontal and left temporal lobes: A case report.

Background: Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disorder affecting many behaviors in daily life. Hyperactivity of the fronto-striato-thalamic circuit via the orbitofrontal cortex (OFC) is assumed to play a major role in the pathophysiology of OCD; however, its pathogenesis is not fully understood. Several reports have described the development of OCD after traumatic brain injury (TBI); however, the pathogenesis of post-TBI OCD remains unknown. Moreover, patients with TBI often have a variety of sequelae, including cognitive dysfunction and mood disorders, which make the diagnosis and treatment of OCD more complex. Case presentation: We report the case of a 17-year-old Japanese male who developed OCD after traffic trauma. The patient developed a fear of contamination and checking compulsion after injuring his right OFC and left temporal lobe when he ran into a running truck during a suicide attempt. We believe that the patient's fear of contamination can be diagnosed as true post-TBI OCD. However, his memory impairment was significant, and we considered his checking compulsion to be strongly influenced by cognitive dysfunction due to TBI. We attempted behavioral therapy for OCD; however, sufficient results were not achieved because of the interference from the sequelae of TBI. Conclusion: It is not rare for OCD symptoms to appear after TBI. Differentiating the OCD symptoms induced by brain injury or cognitive dysfunction associated with TBI is important to determine a treatment strategy.

Multiphoton-Driven Photocatalytic Defluorination of Persistent Perfluoroalkyl Substances and Polymers by Visible Light.

Perfluoroalkyl substances (PFASs) and fluorinated polymers (FPs) have been extensively utilized in various industries, whereas their extremely high stability poses environmental persistence and difficulty in waste treatment. Current decomposition approaches of PFASs and FPs typically require harsh conditions such as heating over 400 °C. Thus, there is a pressing need to develop a new technique capable of decomposing them under mild conditions. Here, we demonstrated that perfluorooctanesulfonate (PFOS), known as a "persistent chemical," and Nafion, a widely utilized sulfonated FP for ion-exchange membranes, can be efficiently decomposed into fluorine ions under ambient conditions via the irradiation of visible LED light onto semiconductor nanocrystals (NCs). PFOS was completely defluorinated within 8-h irradiation of 405-nm LED light, and the turnover number of the C-F bond dissociation per NC was 17200. Furthermore, 81 % defluorination of Nafion was achieved for 24-h light irradiation, demonstrating the efficient photocatalytic properties under visible light. We revealed that this decomposition is driven by cooperative mechanisms involving light-induced ligand displacements and Auger-induced electron injections via hydrated electrons and higher excited states. This study not only demonstrates the feasibility of efficiently breaking down various PFASs and FPs under mild conditions but also paves the way for advancing toward a sustainable fluorine-recycling society.

In vivo mitral valve repair for the transplanted donor heart in orthotopic heart transplantation.

A 53-year-old woman with the dilated phase of hypertrophic cardiomyopathy underwent orthotopic heart transplantation. The donor heart was evaluated as normal preoperatively without mitral regurgitation or the left atrium dilation, transplanted using the modified bicaval technique. Although the heart beat satisfactorily after aortic declamping, massive mitral regurgitation was observed without any prolapse or annular dilation. Because of the difficulty in weaning from cardiopulmonary bypass, a second aortic cross-clamp was applied, and we detached the inferior vena cava and the right side of the left atrial anastomosis to approach the mitral valve, obtaining a satisfactory exposure. No abnormalities were observed in the mitral valve leaflets, annulus or subvalvular apparatus. Subsequent in vivo mitral annuloplasty using prosthetic full ring successfully controlled the regurgitation, and the patient was easily weaned from cardiopulmonary bypass. She discharged to home with good mitral valve and cardiac functions. And the patient has been doing well without any recurrence of MR or heart failure for over a year after surgery.

How should cardiac xenotransplantation be initiated in Japan?

The world's first clinical cardiac xenotransplantation, using a genetically engineered pig heart with 10 gene modifications, prolonged the life of a 57-year-old man with no other life-saving options, by 60 days. It is foreseeable that xenotransplantation will be introduced in clinical practice in the United States. However, little clinical or regulatory progress has been made in the field of xenotransplantation in Japan in recent years. Japan seems to be heading toward a "device lag", and the over-importation of medical devices and technology in the medical field is becoming problematic. In this review, we discuss the concept of pig-heart xenotransplantation, including the pathobiological aspects related to immune rejection, coagulation dysregulation, and detrimental heart overgrowth, as well as genetic modification strategies in pigs to prevent or minimize these problems. Moreover, we summarize the necessity for and current status of xenotransplantation worldwide, and future prospects in Japan, with the aim of initiating xenotransplantation in Japan using genetically modified pigs without a global delay. It is imperative that this study prompts the initiation of preclinical xenotransplantation research using non-human primates and leads to clinical studies.

Advance care planning in the treatment of implantable left ventricular assist device: a republication of the review published in Japanese Journal of Artificial Organs.

Advance care planning (ACP) is essential in managing serious and chronic illnesses to ensure that patients receive care aligned with their personal values, goals, and preferences. This review focuses on integrating ACP in the treatment of patients receiving implantable left ventricular assist devices (VADs). The heart failure palliative care team developed a unique advance directive form and pamphlet to facilitate ACP discussions, emphasizing not only medical treatment preferences but also patients' values and life goals.The study highlights the distinction between bridge to transplantation (BTT) and destination therapy (DT) in VAD patients, with different goals and considerations for ACP. The use of decision aids developed especially for DT candidates as a communication tool helps in sharing patients' wishes and facilitates shared decision-making, particularly in the complex decisions surrounding DT therapy.Challenges in implementing ACP, such as time constraints due to urgent medical conditions, difficulties in patient communication, and the recent COVID-19 pandemic, are addressed. The need for a comprehensive healthcare system capable of supporting patients' ACP wishes, especially in the community setting, is also pointed out.Future directions include not only developing materials to ease ACP discussions and ensuring that ACP content is shared among healthcare providers to foster collaborative and detailed planning, but also a call for widespread adoption of ACP in Japan.This is a translation of a paper written in Japanese Journal of Artificial Organs (Vol. 52, No. 1, pp. 89-92) with additions and corrections.

Restrictive annuloplasty or replacement on reverse remodeling for nonischemic dilated cardiomyopathy.

BACKGROUND: For patients with nonischemic dilated cardiomyopathy (NIDCM), the indications for and results of mitral surgery remain controversial. We reviewed a strategy of mitral repair and replacement for clinically relevant secondary mitral regurgitation (MR) in patients with NIDCM. METHODS: We retrospectively reviewed 65 patients with advanced NIDCM (LVEF < 40%) who underwent mitral surgery. Of them, 47 (72%) underwent mitral annuloplasty and 18 (28%) replacement for secondary MR. The primary endpoint was postoperative reduction in indexed LV end-systolic volume (LVESVI). RESULTS: At baseline, there was no intergroup difference in LVESVI (123 ± 47 vs. 147 ± 37 ml/m2, P = 0.055), LVEF (27 ± 8% vs. 25 ± 6%, P = 0.41), incidence of severe MR (57% (27/47) vs. 72% (13/18), P = 0.40), or EuroSCORE II score (6.2% vs. 7.6%, P = 0.90). At 6 months, the annuloplasty group reduced LVESVI to a greater degree than the replacement group (P < 0.001), yielding significantly smaller postoperative LVESVI (96 ± 59 vs. 154 ± 61 ml/m2, P < 0.001) and better LVEF (P < 0.001). The rates of moderate/severe recurrent MR were 17% (8/47) and 0%, respectively. Multivariable analysis demonstrated that mitral annuloplasty (OR 6.10, 95% CI 1.14-32.8, P = 0.035) was significantly associated with postoperative LV reverse remodeling. Cumulative survival was not different between the groups (P = 0.26). CONCLUSIONS: In patients with NIDCM, mitral annuloplasty reduced LV volume to a greater degree than did mitral replacement. These findings may assist with surgical options for secondary MR associated with NIDCM.

Left ventricular assist device temporary explantation as a strategy for infection control in a pediatric patient.

We report a case of temporary Berlin Heart EXCOR® explantation in a pediatric patient with idiopathic dilated cardiomyopathy who suffered an uncontrollable inflow cannulation site infection while on bridge-to-transplantation. Despite failure to thrive and catheter-related infections, once free of the device, the patient was cured of infection using systemic antibiotics and surgical debridement. The patient underwent EXCOR® reimplantation after four months, and is awaiting heart transplantation in stable condition. A life-threatening ventricular assist device-related infection may require device explantation under conditions that may not fulfill conventional explantation criteria despite risks. Temporary explantation can be an effective strategy if isolated systolic dysfunction is managed carefully.

Formation of the NLRP3 inflammasome inhibits stress granule assembly by multiple mechanisms.

Proper regulation of cellular response to environmental stress is crucial for maintaining biological homeostasis and is achieved by the balance between cell death processes, such as the formation of the pyroptosis-inducing NLRP3 inflammasome, and pro-survival processes, such as stress granule (SG) assembly. However, the functional interplay between these two stress-responsive organelles remains elusive. Here, we identified DHX33, a viral RNA sensor for the NLRP3 inflammasome, as a SG component, and the SG-nucleating protein G3BP as an NLRP3 inflammasome component. We also found that a decrease in intracellular potassium (K+) concentration, a key 'common' step in NLRP3 inflammasome activation, markedly inhibited SG assembly. Therefore, when macrophages are exposed to stress stimuli with the potential to induce both SGs and the NLRP3 inflammasome, such as cytoplasmic poly(I:C) stimulation, they preferentially form the NLRP3 inflammasome but avoid SG assembly by sequestering G3BP into the inflammasome and by inducing a reduction in intracellular K+ levels. Thus, under such conditions, DHX33 is primarily utilized as a viral RNA sensor for the inflammasome. Our data reveal the functional crosstalk between NLRP3 inflammasome-mediated pyroptosis and SG-mediated cell survival pathways and delineate a molecular mechanism that regulates cell-fate decisions and anti-viral innate immunity under stress.

Heart transplantation using a donor heart with repaired tetralogy of Fallot: a case report.

Background: Heart transplantation is the gold standard therapy for end-stage heart failure; however, it is limited by a shortage of available donors. In recent years, heart transplantations have been performed using marginal donor hearts with valvular and/or congenital cardiac abnormalities. Case summary: A 60-year-old woman with acromegalic cardiomyopathy underwent left ventricular assist device implantation and aortic valve (AV) closure 4 years prior. After 2 months, repeat AV closure and omental flap transposition were performed. During the outpatient follow-up, the patient developed recurrent severe AV regurgitation and bacteraemia-induced subarachnoid haemorrhage. She underwent urgent heart transplantation using a marginal donor heart with preserved cardiac function, mild pulmonary valve stenosis, and regurgitation after pulmonary valve-sparing tetralogy of Fallot (TOF) repair. An anatomical anastomosis was possible. She had no signs of infection, heart failure, arrhythmia, or immune rejection 15 months after the heart transplantation. Discussion: In this case, the donor heart with repaired TOF did not require pulmonary valve replacement and was anatomically intact. Donor hearts with repaired TOF that are expected to have long-term durability in terms of cardiac function may be used for successful heart transplantations. The repair of marginal donor hearts creates an opportunity to increase the number of viable donors.

Novel Knowledge of Macrolide Resistance in Mycoplasma pneumoniae by Azithromycin Exposure.

The rise of macrolide-resistant Mycoplasma pneumoniae (MRMP), marked by point mutations in the 23S rRNA gene, poses a growing global concern since its initial detection in 2001. The prominence of the A2063G mutation during this emergence remains unexplained. This study aimed to clarify the possibility of detecting MRMP from recent clinical macrolide-susceptible M. pneumoniae through exposure to azithromycin (AZM), which has a long half-life and was launched immediately before the first MRMP detection. Six strains isolated from Japanese children in 2019 and reference strain (FH), all belonging to the recent dominant P1 genotype, two, or two subtype, were cultivated in a medium containing slightly higher concentrations than the originated minimum inhibitory concentration (MIC) of AZM and underwent sequencing if they grew. Four out of the seven strains grew after exposure to AZM, and C2617G and C2617A were detected, with no mutation in two strains. After another cultivation and sequencing, two of four strains grew, one was changed from C2617G to A2063G, and the other remained C2617A. The MIC of AZM in A2063G strains was 128 mg/mL; for C2617A, it was 0.0156 mg/mL. This is the first study to detect the strains with A2063G mutation from recent macrolide-susceptible M. pneumoniae using AZM exposure.

Three-step surgical management algorithm for annular rupture in transcatheter aortic valve replacement.

Objective: Whereas transcatheter aortic valve replacement is widely implemented, annular rupture is a devastating complication and could be highly mortal. However, owing to its rare incidence, the optimal treatment algorithm has not been established. Thus, we evaluated the feasibility and effectiveness of a 3-step algorithm to treat annulus rupture. Methods: From 2009 to 2022, 8 patients of 1083 transcatheter aortic valve implantation (0.8%) developed annulus rupture and were treated with the three-step algorithm. The algorithm was composed of a first step (pericardial drainage and protamine neutralization with blood pressure control), second step (manual hemostatic compression via full/partial sternotomy), and a third step (conservative treatment or radical surgical correction). Results: The median age at the procedure was 85 (78-88) years and 7 female patients were included in this study. Two (25%) patients had end-stage renal failure under hemodialysis, and median Society of Thoracic Surgeons score was 8.9% (2.1%-23.2%). The implanted transcatheter heart valves (THVs) were 7 balloon-expandable THVs and 1 self-expandable THV with balloon postdilatation. Under this strategy, 8 (100%) patients underwent pericardial drainage as first step and 5 patients achieved hemostasis. Of these, patient 1 demonstrated bleeding from left sinus of Valsalva and required a Bentall procedure. Although the etiology of this phenomenon was not investigated by contrast-enhanced computed tomography, it might be derived from pseudoaneurysm rupture or delayed annular rupture. In 2 patients, the second step treatment was needed for hemostasis. Third-step treatment was conducted in 1 patient. Postoperatively, 6 patients could be discharged without critical complications whereas 2 patients died during the hospitalization. There were no other complications during the followed-up (584 [7-1614]) days. Conclusions: In accordance with the three-step algorithm, 6 patients, including those with high-risk or inoperative status, survived.

Adequate diagnosis of the cause of Parkinsonism and treatment in an elderly patient with schizophrenia: A case report.

Background: Parkinsonism is frequently observed in patients with schizophrenia, and most patients are diagnosed with drug-induced parkinsonism. However, comorbidity with idiopathic Parkinson's disease or Parkinson-plus syndrome is also possible. The pathophysiology and treatment for each of these are entirely different, thus an appropriate diagnosis is required. However, distinguishing them based on clinical symptoms alone is often difficult, and many cases are misdiagnosed. Additionally, Parkinsonism is frequently mistaken for negative symptoms. Case Description: We report a case of 68-year-old woman diagnosed with schizophrenia, who was admitted to a welfare center. At approximately age 60, the patient experienced motivation reduction, a loss of appetite, and pain in the extremities. In her mid-60s, tremor and muscle rigidity appeared; nuclear medicine testing was performed for a detailed examination, resulting in a diagnosis of levodopa-responsive Parkinson's syndrome. Notably, the patient's parkinsonism and emotional symptoms, which had been considered negative symptoms thus far, improved with levodopa treatment. Conclusion: This case report illustrates the importance of properly diagnosing the cause of parkinsonism in patients with schizophrenia.