[Diagnosis and treatment of aplastic anemia and lower-risk myelodysplastic neoplasms].

Myelodysplastic neoplasms (MDS) are clonal hematological malignancies arising from gene mutations. Immunosuppressive therapies (IST) are effective in lower-risk MDS (LR-MDS) with characteristics such as hypoplastic marrow with low blasts or low ring sideroblasts, and with a small increase of PNH clones or decrease of megakaryocytes. Differential diagnosis of these LR-MDS cases from AA can be difficult, and precise diagnosis requires careful evaluation of bone marrow cellularity and dysplasia. To decide on an appropriate treatment strategy for LR-MDS, it is important to evaluate the underlying pathology, and preferentially select IST as first-line therapy in patients with features that indicate immune-mediated bone marrow failure.

Skill Mastery and Learning Curve Analysis in Fenestrated Endovascular Aortic Repair with Physician-Modified Endograft.

Objectives: This study aims to delineate the unique learning curve for fenestrated endovascular aortic repair (FEVAR) at our institution. Materials and Methods: We measured the FEVAR-specific procedure time (FSPT) as the duration from device deployment to bridging stent completion. To maintain consistency in technical complexity, the study focused on 38 cases with four-fenestration FEVAR for juxtarenal abdominal aortic aneurysms, selected from 103 of all FEVAR procedures between June 2011 and February 2024. In these cases, superior mesenteric and bilateral renal arteries were preserved with fenestration with bridging stents insertion, while celiac arteries fenestrations without fenestrations. Learning curve and cumulative sum (CUSUM) analyses assessed FSPT reduction against increased FEVAR experiences. Results: A significant learning curve was observed, with the procedure time (y) and experience (X) correlation given by y = -39.95 log(X) + 283.6 (R2 = 0.5758). CUSUM indicated that 30 to 50 cases were required for skill stabilization and maturation. Conclusion: Our endovascular team required 30-50 cases to establish reliable FEVAR proficiency. Beyond cumulative experiences, pivotal elements in the learning trajectory seemed to include technological advancements and team augmentation.

Correlation Between Subgenome-biased DNA Loss and DNA Transposon Activation Following Hybridization in the Allotetraploid Xenopus Frogs.

In certain tetraploid species resulting from interspecific hybridization, one parent's subgenome is known to selectively undergo DNA loss. The molecular mechanisms behind this remain unclear. In our study, we compared the genomes of a standard diploid species with two allotetraploid species from the Xenopus genus, both possessing L (longer) and S (shorter) homoeologous subgenomes. We observed substantial gene losses and intergenic DNA deletions in both the S and L subgenomes of the tetraploid species. Gene losses were around 1,000 to 3,000 for L and 4,000 to 6,000 for S, with especially prominent losses in the S subgenome. Many of these losses likely occurred shortly after interspecific hybridization in both L/S subgenomes. We also deduced frequent large inversions in the S subgenome. Upon reassessing transposon dynamics using updated genome databases, we reaffirmed heightened DNA transposon activity during the hybridization, as previously reported. We next investigated whether S subgenome-biased DNA loss could be correlated with the activation of DNA transposons following hybridization. Notably, distinct patterns were observed in the dynamics of DNA transposons between the L and S subgenomes. Several DNA transposon subfamilies correlated positively with DNA deletions in the S subgenome and negatively in the L subgenome. Based on these results, we propose a model that, upon and after hybridization between two related diploid Xenopus species, the mixture of their genomes resulted in the derepression of DNA transposons, especially in the S subgenome, leading to selective DNA loss in the S subgenome.

In vitro immuno-prevention of nitration/dysfunction of myogenic stem cell activator HGF, towards developing a strategy for age-related muscle atrophy.

In response to peroxynitrite (ONOO-) generation, myogenic stem satellite cell activator HGF (hepatocyte growth factor) undergoes nitration of tyrosine residues (Y198 and Y250) predominantly on fast IIa and IIx myofibers to lose its binding to the signaling receptor c-met, thereby disturbing muscle homeostasis during aging. Here we show that rat anti-HGF monoclonal antibody (mAb) 1H41C10, which was raised in-house against a synthetic peptide FTSNPEVRnitroY198EV, a site well-conserved in mammals, functions to confer resistance to nitration dysfunction on HGF. 1H41C10 was characterized by recognizing both nitrated and non-nitrated HGF with different affinities as revealed by Western blotting, indicating that the paratope of 1H41C10 may bind to the immediate vicinity of Y198. Subsequent experiments showed that 1H41C10-bound HGF resists peroxynitrite-induced nitration of Y198. A companion mAb-1H42F4 presented similar immuno-reactivity, but did not protect Y198 nitration, and thus served as the control. Importantly, 1H41C10-HGF also withstood Y250 nitration to retain c-met binding and satellite cell activation functions in culture. The Fab region of 1H41C10 exerts resistivity to Y250 nitration possibly due to its localization in the immediate vicinity to Y250, as supported by an additional set of experiments showing that the 1H41C10-Fab confers Y250-nitration resistance which the Fc segment does not. Findings highlight the in vitro preventive impact of 1H41C10 on HGF nitration-dysfunction that strongly impairs myogenic stem cell dynamics, potentially pioneering cogent strategies for counteracting or treating age-related muscle atrophy with fibrosis (including sarcopenia and frailty) and the therapeutic application of investigational HGF drugs.

Depth detection limit of a fluorescent object in tissue-like medium with background emission in continuous-wave measurements: a phantom study.

Significance: Although the depth detection limit of fluorescence objects in tissue has been studied, reports with a model including noise statistics for designing the optimum measurement configuration are missing. We demonstrate a variance analysis of the depth detection limit toward clinical applications such as noninvasively assessing the risk of aspiration. Aim: It is essential to analyze how the depth detection limit of the fluorescence object in a strong scattering medium depends on the measurement configuration to optimize the configuration. We aim to evaluate the depth detection limit from theoretical analysis and phantom experiments and discuss the source-detector distance that maximizes this limit. Approach: Experiments for detecting a fluorescent object in a biological tissue-mimicking phantom of ground beef with background emission were conducted using continuous wave fluorescence measurements with a point source-detector scheme. The results were analyzed using a model based on the photon diffusion equations. Then, variance analysis of the signal fluctuation was introduced. Results: The model explained the measured fluorescence intensities and their fluctuations well. The variance analysis showed that the depth detection limit in the presence of ambient light increased with the decrease in the source-detector distance, and the optimum distance was in the range of 10 to 15 mm. The depth detection limit was found to be ∼ 30 mm with this optimum distance for the phantom. Conclusions: The presented analysis provides a guide for the optimum design of the measurement configuration for detecting fluorescence objects in clinical applications.

Exploratory Online Survey Regarding Perceptions of Health Inequities Influenced by Social Determinants of Health Among Cardiovascular Disease Patients.

Despite establishing conventional risk factors and preventive medicine for cardiovascular diseases (CVD), there remains a notable lack of research for identifying social determinants of health (SDOH). The aim of this study was to identify the SDOH domains contributing to health inequities perceived by Japanese CVD citizens. An online survey was conducted among 2,083 Japanese CVD patients from November 7 to 13, 2023, to assess their perceptions of 19 social determinants of health (SDOH) domains and their impact on health inequities. Using the 5-point Likert scale, a high level of agreement was defined as over 50% selecting "Agree" or "Strongly Agree." The "Health inequity perception score (HIPS)" was calculated by assigning 1 point for 'Agree' and 2 points for 'Strongly Agree.' Additionally, patient factors that defined a group with HIPS above the median were also evaluated. High agreement was noted in 7 out of 19 domains: "Employment" (61%), "Food Insecurity" and "Environmental Condition" (each at 60%), "Poverty" (58%), "Early Childhood Development and Education" (57%), "Housing Instability and Quality" (56%), and "Access to Health Service" (52%). Young age, high annual income, high educational level, and living alone were significantly associated with high HIPS. This study highlights that several SDOH factors commonly acknowledged in Western contexts are also recognized as contributors to health inequities among Japanese CVD patients.

Propelling Nurse-Led Structured Intervention to Enhance Self-Care among Patients with Chronic Heart Failure (PROACT-HF): A Cluster Randomized Controlled Trial Study Protocol.

BACKGROUND: Heart Failure (HF) is a common chronic disease that has a high readmission rate and is associated with worsening symptoms and major financial impacts. Disease management implemented during or after an HF hospitalization has been shown to reduce hospitalization and mortality rates. Particularly for outpatients, it is necessary to provide self-care interventions. Structured nurse-led support such as timely follow-ups, including phone calls, is beneficial for improving self-care assessments. Evidence for nurse-led support has been investigated but is less than conclusive. The aim of this study is to compare the effectiveness of a nurse-led structured intervention for outpatients with chronic HF against the usual medical care in terms of self-care behaviors and occurrence of symptom exacerbation or rehospitalization. METHODS AND ANALYSIS: This is a cluster-randomized controlled trial. A total of 40 facilities with certified HF nurses will be allocated to two-arm clusters at a 1:1 ratio, randomly to the intervention or usual care arms. A total of 210 participants will be assigned from the hospital. Participants will be adults aged 18 years or older diagnosed with chronic HF who are classified as Stage C according to the ACCF/AHA Heart Failure staging system. In the intervention group, patients will receive structured nursing support. This begins with weekly support, including phone calls, for the first month, then transitions to monthly support thereafter. The aim is to ensure the stability of their living conditions, promote medication adherence, and encourage self-management. In the control group, patients will receive the usual care. Primary outcomes will assess the improvement or continuation of self-care behavior as measured by changes in EHFScBS (European Heart Failure Self-Care Behavior Scale) scores. Secondary outcomes include occurrence of readmission within 30 days, 3 months, 6 months, and 1 year after discharge, duration of home care until readmission, and blood levels of BNP and NT-proBNP.

Impact of off-hours admissions in STEMI-related cardiogenic shock managed with microaxial flow pump - insights from J-PVAD.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock (STEMI-CS) is associated with high mortality rates. Patients admitted during off-hours, specifically on weekends and at night, show higher mortality rates, which is called the "off-hours effect". The off-hours effect in patients with STEMI-CS treated with mechanical circulatory support, especially Impella, has not been fully evaluated. AIMS: We aimed to investigate whether off-hours admissions were associated with higher mortality rates in this population. METHODS: We used large-scale Japanese registry data for consecutive patients treated with Impella between February 2020 and December 2021 and compared on- and off-hours admissions. On- and off-hours were defined as the time between 8:00 and 19:59 on weekdays and the remaining time, respectively. The Cox proportional hazards model was used to calculate the adjusted hazard ratios (aHRs) for 30-day mortality. RESULTS: Of the 1,207 STEMI patients, 566 (46.9%) patients (mean age: 69 years; 107 females) with STEMI-CS treated with Impella were included. Of these, 300 (53.0%) were admitted during on-hours. During the follow-up period (median 22 days [interquartile range 13-38 days]), 112 (42.1%) and 91 (30.3%) deaths were observed among patients admitted during off- and on-hours, respectively. Off-hours admissions were independently associated with a higher risk of 30-day mortality than on-hours admissions (aHR 1.60, 95% confidence interval: 1.07-2.39; p=0.02). CONCLUSIONS: Our findings indicated the persistence of the "off-hours effect" in STEMI-CS patients treated with Impella. Healthcare professionals should continue to address the disparities in cardiovascular care by improving the timely provision of evidence-based treatments and enhancing off-hours medical services.

Left-digit bias in out-hospital cardiac arrest: The JCS-ReSS study.

INTRODUCTION: The left-digit bias (LDB), a numerical-related cognitive bias, not only potentially influences decision-making among the general public but also that of medical practitioners. Few studies have investigated its role in out-of-hospital cardiac arrest (OHCA). METHODS: We retrospectively included all consecutive patients with OHCA witnessed by family members registered in the All-Japan Utstein Registry of the Fire and Disaster Management Agency between January 1, 2005, and December 31, 2020. Target outcomes were the percentage of bystander cardiopulmonary resuscitation (BCPR) performed by family members or paramedics and the percentage of prehospital physician-staffed advanced cardiac life support (ACLS). Using a nonparametric regression discontinuity methodology, we examined whether a significant change occurred in the percentages of BCPR and ACLS at the age thresholds of 60, 70, 80, and 90 years, which would indicate the presence of LDB. RESULTS: Of the 1,930,273 OHCA cases in the All-Japan Utstein Registry, 384,200 (19.9%) cases witnessed by family members were analyzed. The mean age was 75.8 years (±SD 13.7), with 38.0% (n = 146,137) female. We identified no discontinuities in the percentages of chest compressions, mouth-to-mouth ventilation, or automated external defibrillator (AED) usage by family members for the age thresholds of 60, 70, 80, and 90 years. Moreover, no discontinuities existed in the percentages of chest compressions, advanced airway management, and AED usage by paramedics or prehospital ACLS by physicians for any of the age thresholds. CONCLUSIONS: In conclusion, our study did not find any evidence that age-related LDB affects medical decision-making in patients with OHCA.

Bereaved family members' perspectives on quality of death in deceased acute cardiovascular disease patients compared with cancer patients - a comparison of the J-HOPE3 study and the quality of palliative care in heart disease (Q-PACH) study.

BACKGROUND: Outcome measures during acute cardiovascular disease (CVD) phases, such as quality of death, have not been thoroughly evaluated. This is the first study that compared the family members' perceptions of quality of death in deceased CVD patients and in deceased cancer patients using a bereaved family survey. METHODS: Retrospectively sent questionnaire to consecutive family members of deceased patients with CVD from ten tertiary hospitals from October 2017 to August 2018. We used the short version of the Good Death Inventory (GDI) and assessed overall care satisfaction. Referencing the GDI, the quality of death was compared between CVD patients admitted to a non-palliative care unit (non-PCU) and cancer patients in palliative care units (PCU) and non-PCUs in the Japan Hospice and Palliative Care Evaluation Study (J-HOPE Study). Additionally, in the adjusted analysis, multivariable linear regression was performed for total GDI score adjusted by the patient and participant characteristics to estimate the difference between CVD and other patients. RESULTS: Of the 243 bereaved family responses in agreement (response rate: 58.7%) for CVD patients, deceased patients comprised 133 (54.7%) men who were 80.2 ± 12.2 years old on admission. The GDI score among CVD patients (75.0 ± 15.7) was lower (worse) than that of cancer patients in the PCUs (80.2 ± 14.3), but higher than in non-PCUs (74.4 ± 15.2). After adjustment, the total GDI score for CVD patients was 7.10 points lower [95% CI: 5.22-8.97] than for cancer patients in PCUs and showed no significant differences compared with those in non-PCUs (estimates, 1.62; 95% CI [-0.46 to 5.22]). CONCLUSIONS: The quality of death perceived by bereaved family members among deceased acute CVD patients did not differ significantly from that of deceased cancer patients in general wards, however, was significantly lower than that of deceased cancer patients admitted in PCUs.

Case report: Gait-induced palilalia in a patient with hemiplegia due to cerebral infarction.

Background: Palilalia is a type of speech characterized by compulsive repetition of words, phrases, or syllables. Several reports have noted that palilalia can occur in response to external verbal stimuli. Here, we report, for the first time, a patient with palilalia induced by gait, which we call "movement-related palilalia." Case presentation: Eleven months after the onset of cerebral infarction sparing the right precentral gyrus and its adjacent subcortical regions, a 63-year-old, left-handed Japanese man was referred for psychiatric consultation because of a complaint of irritability caused by the stress of compulsive repetition of a single meaningless word, "wai." The repetition of a word, palilalia, in this case, was characterized by its predominant occurrence during walking and by its melodic tones. The palilalia during walking disappeared almost completely after 5 months of treatment with carbamazepine 600 mg. Conclusion: Palilalia induced by gait can occur in patients with a history of cerebral infarction. This palilalia during walking may be due to the reorganization of networks in areas nearby or surrounding cerebral infarcts.

Streptococcal Toxic Shock Syndrome with Multiple Cerebral Infarctions Caused by Streptococcus dysgalactiae subsp. equisimilis: An Autopsy Case Report.

We herein report an autopsy case of streptococcal toxic shock syndrome with disseminated intravascular coagulation and multiple cerebral infarctions induced by Streptococcus dysgalactiae subsp. equisimilis (STSS) in an 84-year-old male. Pathological examination revealed sepsis with hemophagocytosis in the reticular system and intravascular bacteria in multiple organs, originating from bacterial necrotizing fasciitis of the lower extremities. The brain MRI findings showed a DWI-FLAIR mismatch, whereas the pathology was almost normal, thus supporting a hyperacute phase of cerebral infarction. The findings in this case help to elucidate the pathogenesis of STSS and develop appropriate treatment strategies.

Remodeling of the Proximal Sealing Zone and Sac Shrinkage after Endovascular Aortic Repair or Fenestrated Endovascular Aortic Repair.

BACKGROUND: Variations in sac shrinkage (SS) are noted between endovascular aneurysm repair for abdominal aortic aneurysm (AAA) and fenestrated endovascular aneurysm repair for short neck AAA. These variations may originate from difference in the geometry and length of proximal sealing, which influences the quality and durability of the seal. This study aimed to explore the disparities in aneurysm exclusion and sac remodeling across these 2 scenarios. METHODS: This study involved a retrospective analysis of prospectively collected data from 2014 to 2021. Of 486 endovascular abdominal aortic repair cases, 33 that exclusively used a low permeability expanded polytetrafluoroethylene infrarenal device, strictly adhering to the instructions for use (IFUs), were selected. Concurrently, 30 cases of fenestrated repair that utilized modified polyester woven fabric devices proximally with consistent use of the aforementioned low-permeability devices infrarenally were examined. The quality of both proximal and distal sealing zones in fenestrated repairs was maintained within the range specified in the expanded polytetrafluoroethylene infrarenal device's IFUs, ensuring consistent sealing integrity for reliable group comparisons. Key metrics used for analysis were the detection of endoleaks and measurements of sac dimensions. Additional analyses included comparisons of demographic data and postoperative diameter changes in the proximal sealing zone (PZ) (encompassing 0, 5, 10, 15, and 20 mm below the most proximal sealing stent). RESULTS: The demographic data and preoperative maximum-minimum diameter of the aneurysms did not differ between the groups. Proximal neck dilatation was similarly observed after both procedures. Immediately after the procedure, the incidence of lumbar arterial type II endoleaks was significantly lower after fenestrated repair than that after endovascular aortic repair (EVAR, 10% vs. 39.4%, P = 0.0094). At the final observation, EVAR substantially reduced the PZ length (-4.73 ± 15.30%), while fenestrated repair maintained the length (21.98 ± 24.34%; P < 0.0001). The preservation of the sealing length in fenestrated repairs was attributable to dilation occurring within the sealing range of the proximal device, oversized to accommodate the larger diameters in the more proximal sections of the aorta. The cumulative occurrence of SS (>5 mm) following fenestrated repair increased faster than that after endovascular repair (P = 0.002). CONCLUSIONS: Although aortic neck dilatation progressed similarly in both groups, fenestrated repair maintained the sealing length and demonstrated a greater extent of SS, even under the challenging circumstances in PZ. The superior postoperative results were linked to both the durability of proximal sealing and a lower occurrence of lumbar arterial type II endoleaks, stemming from the effective shuttering of the collateral sources in the proximal lumbar or intercostal arteries.

Thymic MALT lymphoma associated with Sjögren's syndrome with postoperative cardiac tamponade and acute pleuritis: a case report.

BACKGROUND: Thymic mucosa-associated lymphoid tissue (MALT) lymphoma is rare and is known to be associated with Sjögren's syndrome (SjS). SjS is rarely accompanied by serositis. Here, we describe the first case of postoperative cardiac tamponade and acute pleuritis in a patient with thymic MALT lymphoma associated with SjS. CASE PRESENTATION: A 33-year-old woman with SjS presented with an anterior mediastinal mass on chest computed tomography, which was performed for further examination of the condition. Suspecting a thymic MALT lymphoma or thymic epithelial tumor, total thymectomy was performed. The mediastinal mass was histopathologically diagnosed as a thymic MALT lymphoma. The patient was discharged with a good postoperative course but visited the hospital 30 days after surgery for dyspnea. Cardiac tamponade was observed and drainage was performed. Four days after pericardial drainage, chest radiography revealed massive left pleural effusion, and thoracic drainage was performed. The patient was diagnosed with serositis associated with SjS and treated with methylprednisolone, which relieved cardiac tamponade and pleuritis. CONCLUSIONS: Surgical invasion of thymic MALT lymphomas associated with SjS may cause serositis. Postoperative follow-up should be conducted, considering the possibility of cardiac tamponade or acute pleuritis due to serositis as postoperative complications.

A Case of Refractory Posterior Scleritis with Marked Retinochoroidal Detachment Associated with Panuveitis.

An 84-year-old man presented with decreased right-eye visual acuity. Upon initial examination, the rightand left-eye visual acuities were 0.03 and 1.2, respectively; moreover, the right- and left-eye intraocular pressure was 12 mmHg and 13 mmHg, respectively. Examination revealed a shallow anterior chamber of the right eye, anterior chamber inflammation, vitreous opacity, and marked retinochoroidal detachment. Optical coherence tomography (OCT) revealed retinal detachment (RD) and choroidal folds; moreover, B-scan ultrasonography (B-scan) showed RD as well as thickened sclera with fluid in Tenon's space. Fluorescent fundus angiography revealed hyperfluorescence in the optic disc and vascular hyperpermeability in the right eye. The left eye lacked extra-ocular symptoms or abnormalities. The right ocular axis measured 23.4 mm with no apparent subretinal fluid migration due to positional changes. Accordingly, the patient was diagnosed with panuveitis associated with posterior scleritis and immediately started on 40 mg prednisolone, which improved his symptoms. However, at 3 post-treatment months, choroidal folds were observed and was restarted on 20 mg prednisolone. The choroidal folds subsequently disappeared, with a current visual acuity of 0.3 in the right eye and no recurrence. Our findings indicated the utility of accurate diagnosis of posterior scleritis by B-scan and prompt systemic steroid administration.

Comparison of Intraocular Lens Location Between Suture Fixation and Intrascleral Sutureless Fixation Procedure.

OBJECTIVE: Two methods are available for intraocular lens (IOL) insertion when the lens capsule is unavailable, including suture and sutureless fixations in which the IOL haptics are fixed in the sclera. The IOL position and refractive error after both procedures were compared. METHODS: Data were retrospectively extracted from patients who underwent IOL insertion at our institution by suture or sutureless fixation (suture fixation: 12 eyes and sutureless fixation: 15 eyes). The postoperative IOL tilt angle and decentration distance were automatically calculated. The difference between the postoperative refractive error and the preoperative expected refractive value was determined and statistically investigated. RESULTS: IOL position, tilt, and decentration were not significantly different between the two groups, but the refractive difference was significantly lower in the sutureless fixation group (P = 0.035). No significant correlation was found between IOL position and refractive difference. CONCLUSIONS: Short-term results reveal that both the suture and sutureless fixation groups performed well, with no significant deviation in IOL tilt and decentration compared to previous reports. However, suture fixation was significantly more prone to refractive differences than sutureless fixation.

FLI1 is associated with regulation of DNA methylation and megakaryocytic differentiation in FPDMM caused by a RUNX1 transactivation domain mutation.

Familial platelet disorder with associated myeloid malignancies (FPDMM) is an autosomal dominant disease caused by heterozygous germline mutations in RUNX1. It is characterized by thrombocytopenia, platelet dysfunction, and a predisposition to hematological malignancies. Although FPDMM is a precursor for diseases involving abnormal DNA methylation, the DNA methylation status in FPDMM remains unknown, largely due to a lack of animal models and challenges in obtaining patient-derived samples. Here, using genome editing techniques, we established two lines of human induced pluripotent stem cells (iPSCs) with different FPDMM-mimicking heterozygous RUNX1 mutations. These iPSCs showed defective differentiation of hematopoietic progenitor cells (HPCs) and megakaryocytes (Mks), consistent with FPDMM. The FPDMM-mimicking HPCs showed DNA methylation patterns distinct from those of wild-type HPCs, with hypermethylated regions showing the enrichment of ETS transcription factor (TF) motifs. We found that the expression of FLI1, an ETS family member, was significantly downregulated in FPDMM-mimicking HPCs with a RUNX1 transactivation domain (TAD) mutation. We demonstrated that FLI1 promoted binding-site-directed DNA demethylation, and that overexpression of FLI1 restored their megakaryocytic differentiation efficiency and hypermethylation status. These findings suggest that FLI1 plays a crucial role in regulating DNA methylation and correcting defective megakaryocytic differentiation in FPDMM-mimicking HPCs with a RUNX1 TAD mutation.

Synthesis of dihydrotropone derivatives using an anionic 8π-electrocyclic reaction.

A new method to synthesise functionalised cycloheptatrienes was established using the anionic 8π-electrocyclic reaction of ß-ketoester-derived dienyne substrates. The cyclised products were converted to a variety of cycloheptatriene derivatives including tropones. Using this method, a concise, first total synthesis of (-)-orobanone, a natural sesquiterpenoid, was achieved.

Rocuronium Can Trigger a Hypertensive Crisis in a Patient With Paraganglioma: A Case Report.

We present a case of rocuronium-induced hypertensive crises that occurred twice in a patient with paraganglioma. An 86-year-old woman was first scheduled for laminectomy for lumbar spinal stenosis. Five minutes after intravenous induction of anesthesia using fentanyl, propofol, rocuronium, and remifentanil, the patient's blood pressure (BP) and heart rate (HR) suddenly increased with no stimuli. Surgery was postponed because the patient was suspected of having pheochromocytoma. After that, paraganglioma was diagnosed, and surgery for removal of the paraganglioma was scheduled after the commencement of alpha-blocker therapy. The patient's hemodynamic parameters remained stable when anesthesia was induced with an infusion of remimazolam. Subsequently, immediately after rocuronium was administered as an intravenous bolus, the patient's arterial BP and HR increased, and plasma concentrations of noradrenaline and rocuronium had markedly increased. Ten minutes after the administration of rocuronium, the patient's BP and HR gradually and fully recovered without any intervention. The plasma concentrations of both noradrenaline and rocuronium also concurrently decreased. We conclude that simultaneous increases in BP, HR, and plasma concentration of noradrenaline revealed a direct correlation with rocuronium.

WT1-guided pre-emptive therapy after allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia.

Measurable residual disease (MRD)-guided pre-emptive therapies are now widely used to prevent post-transplant hematological relapse in patients with acute myeloid leukemia (AML). This single-center retrospective study aimed to clarify the significance of pre-emptive treatment based on Wilms' tumor gene-1 mRNA (WT1) monitoring for MRD in patients with AML who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients with AML who received chemotherapy for hematological relapse or WT1 increase after allo-HSCT were eligible for inclusion. From January 2017 to June 2022, 30 patients with a median age of 57 (16-70) years were included and stratified into two groups: 10 with WT1 increase and 20 with hematological relapse. The median times from HCT to WT1 increase or hematological relapse were 309 days (range: 48-985) or 242 days (range: 67-1116), respectively. Less intensive chemotherapy using azacitidine or cytarabine was selected for all patients with WT1 increase and 12 (60%) with hematological relapse. The 1-year overall survival and event-free survival rates for WT1 increase and hematological relapse were 70% vs. 44% (P = 0.024) and 70% vs. 29% (P = 0.029), respectively. These real-world data suggest that WT1-guided pre-emptive therapy may be superior to therapy after hematological relapse in patients with AML who have undergone allo-HSCT.