Day-to-day regularity and diurnal switching of physical activity reduce depression-related behaviors: a time-series analysis of wearable device data.

BACKGROUND: Wearable devices have been widely used in research to understand the relationship between habitual physical activity and mental health in the real world. However, little attention has been paid to the temporal variability in continuous physical activity patterns measured by these devices. Therefore, we analyzed time-series patterns of physical activity intensity measured by a wearable device and investigated the relationship between its model parameters and depression-related behaviors. METHODS: Sixty-six individuals used the wearable device for one week and then answered a questionnaire on depression-related behaviors. A seasonal autoregressive integral moving average (SARIMA) model was fitted to the individual-level device data and the best individual model parameters were estimated via a grid search. RESULTS: Out of 64 hyper-parameter combinations, 21 models were selected as optimal, and the models with a larger number of affiliations were found to have no seasonal autoregressive parameter. Conversely, about half of the optimal models indicated that physical activity on any given day fluctuated due to the previous day's activity. In addition, both irregular rhythms in day-to-day activity and low-level of diurnal variability could lead to avoidant behavior patterns. CONCLUSION: Automatic and objective physical activity data from wearable devices showed that diurnal switching of physical activity, as well as day-to-day regularity rhythms, reduced depression-related behaviors. These time-series parameters may be useful for detecting behavioral issues that lie outside individuals' subjective awareness.

The effectiveness of pretreatment video-based psychoeducation for patients with breast cancer.

OBJECTIVES: This study confirms the effectiveness of pretreatment video-based psychoeducation on stress management and relaxation in reducing depression, anxiety, and uncertainty among patients with breast cancer. METHODS: We conducted a nonrandomized trial with 86 pretreatment patients with breast cancer who were divided equally into intervention and control groups, and stratified according to cancer stages and patient ages. Omitting the excluded participants, 35 intervention group and 36 control group participants were asked to complete the Hospital Anxiety and Depression Scale and Universal Uncertainty in Illness Scale (UUIS) before the psychoeducational intervention (baseline, hereafter "BL ") as well as 1 and 3 months later. Then, a 2 group (intervention and control groups) × 3 time points (BL and 1 and 3 months post-intervention) mixed models repeated measures (MMRM) analysis was implemented. RESULTS: Analysis confirmed interaction between 2 group × 3 time points for depression, anxiety, and UUIS. Multiple comparisons revealed that each score in the intervention group was significantly lower 1 and 3 months post-intervention compared to BL. Meanwhile, in the control group, the depression score was significantly higher at 3 months post-intervention compared to pre-intervention. The anxiety scores and UUIS of the same group were not significantly different between 1 and 3 months post-intervention. The effect size values 3 months post-intervention were -0.57 for depression, -0.25 for anxiety, and 0.05 for uncertainty. SIGNIFICANCE OF RESULTS: Pretreatment psychoeducation reduced depression, anxiety, and uncertainty in the intervention group of patients with breast cancer compared to the control group. The effect sizes at 3 months post-intervention were moderate for depression and small for anxiety. These results suggest the effectiveness of psychoeducation for patients with breast cancer, using videos on stress management and relaxation, early at the pretreatment stage.

Methotrexate mediates the integrity of intestinal stem cells partly through nitric oxide-dependent Wnt/ß-catenin signaling in methotrexate-induced rat ileal mucositis.

This study aimed to elucidate the role of nitric oxide (NO) in intestinal stem cells in methotrexate-induced ileal mucositis in rats. Methotrexate induced the mRNA expressions of the Wnt/ß-catenin target genes Wnt3a, Sox9, and Lgr5 and the Wnt-antagonist gene sFRP-1 and the protein expressions of Lgr5 and sFRP-1. Methotrexate also induced Lgr5+ cells and lysozyme+ cells. A non-selective NO inhibitor inhibited the methotrexate induction of Wnt/ß-catenin target genes and Lgr5+ cells but enhanced that of sFRP-1 expression. Thus, methotrexate mediates the integrity of intestinal stem cells partly through NO-dependent Wnt/ß-catenin signaling and may enhance tolerability to methotrexate-induced injury.

Incidence of fistula occurrence in patients with cervical cancer treated with bevacizumab: data from real-world clinical practice.

BACKGROUND: This study aimed to determine the incidence of pelvic fistulas in cervical cancer patients treated with bevacizumab in Japanese clinical practice. METHODS: A post-marketing surveillance (PMS) study was conducted between June 2016 and February 2018 to survey physicians who treated advanced or recurrent cervical cancer patients with bevacizumab (according to the product label). The clinical/treatment status of patients with pelvic fistulas was assessed in an additional retrospective case series study. RESULTS: 142 patients were included in the PMS study (median age 51 years; 66.9% squamous cell carcinoma; 66.2% recurrent cervical cancer; 64.1% previous radiotherapy). Patients received a median of seven bevacizumab doses. Six patients, all of whom had a history of pelvic irradiation, developed seven fistulas (4.2%; 95% confidence interval, 1.56-8.96), and five patients had also undergone pelvic surgery. The case series study of the patients who developed fistulas indicated that three patients had high cumulative bladder and rectal doses of radiation, and two of them had undergone salvage re-irradiation for pelvic recurrence. The other three patients underwent both radical hysterectomy and adjuvant radiotherapy, but did not receive an excessive radiation dose to the bladder or rectum. CONCLUSIONS: This study found that the upper limit of the 95% confidence interval for pelvic fistula incidence did not exceed the incidence reported in the GOG 240 study. To ensure an adequate benefit-risk assessment of bevacizumab in cervical cancer patients, a comprehensive evaluation of prior treatment is essential and the possibility of unexpected fistulas, even after careful evaluation, should be considered.

Metabolome Shift in Both Metastatic Breast Cancer Cells and Astrocytes Which May Contribute to the Tumor Microenvironment.

The role of astrocytes in the periphery of metastatic brain tumors is unclear. Since astrocytes regulate central nervous metabolism, we hypothesized that changes in astrocytes induced by contact with cancer cells would appear in the metabolome of both cells and contribute to malignant transformation. Coculture of astrocytes with breast cancer cell supernatants altered glutamate (Glu)-centered arginine-proline metabolism. Similarly, the metabolome of cancer cells was also altered by astrocyte culture supernatants, and the changes were further amplified in astrocytes exposed to Glu. Inhibition of Glu uptake in astrocytes reduces the variability in cancer cells. Principal component analysis of the cancer cells revealed that all these changes were in the first principal component (PC1) axis, where the responsible metabolites were involved in the metabolism of the arginine-proline, pyrimidine, and pentose phosphate pathways. The contribution of these changes to the tumor microenvironment needs to be further pursued.

Clinical impact of baseline renal function on safety and early discontinuation of adjuvant capecitabine plus oxaliplatin in elderly patients with resected colon cancer: a multicenter post-marketing surveillance study.

BACKGROUND: Adjuvant capecitabine and oxaliplatin (CAPOX) is a standard treatment for resected colon cancer; however, in patients with moderate renal impairment, the incidence of CAPOX-related adverse events (AEs) and the rate of early discontinuation are higher than in patients with no or mild renal impairment. The aim of this retrospective study was to assess the impact of baseline renal function on the safety and discontinuation of adjuvant CAPOX therapy started with the standard dose of capecitabine in elderly patients with colon cancer. METHODS: Data from patients aged ≥65 years old who received CAPOX at the standard starting dose as adjuvant therapy for stage II/III colon cancer were collected and analyzed retrospectively. Patients were divided into two groups based on their renal function: CLcr-H (patients with a creatinine clearance [CLcr] ≥50 ml/min) and CLcr-L (CLcr <50 ml/min), and AEs and discontinuations were assessed. RESULTS: Overall, 189 patients were assessed (CLcr-H group = 137 and CLcr-L group = 52). No patients experienced grade 4 AEs. The incidence of grade 3 CAPOX-related AEs was higher in the CLcr-L group (42.3%) than in the CLcr-H group (31.3%). The proportion of patients who discontinued treatment within four cycles due to AEs was also higher in the CLcr-L group (21.1%) than in the CLcr-H group (2.9%). Multivariate analysis identified that CLcr <50 ml/min was the only significant risk factor for CAPOX therapy discontinuation due to AEs (P = 0.0008). CONCLUSIONS: This study demonstrates that the tolerability of adjuvant CAPOX therapy was decreased in elderly patients with impaired renal function. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry number UMIN000016446.

Safety and effectiveness of bevacizumab in Japanese patients with malignant glioma: a post-marketing surveillance study.

OBJECTIVE: This surveillance study was conducted to verify the post-market safety and effectiveness of bevacizumab, which was approved in Japan in 2013 for the treatment of patients with newly diagnosed and or recurrent malignant glioma. METHODS: This was a prospective, observational, multicenter post-marketing surveillance study. Patients with newly diagnosed or recurrent malignant glioma scheduled for bevacizumab treatment were enrolled. The incidence and severity of adverse drug reactions were calculated. The effectiveness of bevacizumab was assessed by the 1-year survival rate and the overall survival rate. RESULTS: The safety analysis set and the effectiveness analysis set each comprised 258 of the 268 enrolled patients: tumours were newly diagnosed in 80 patients (31%) and recurrent in 178 patients (68.9%). The incidence of grade ≥ 3 adverse drug reactions was 15.1%. Adverse drug reactions of special interest included 14 cerebral bleeding events and 11 infections. Of the 80 patients with newly diagnosed malignant glioma, 44 (55%) were alive throughout the 18-month observation period. The 1-year survival rate for patients with newly diagnosed glioblastoma was 78%. Median overall survival was not calculated, but 51.2% of patients were alive at the last date of observation of the last observed patient. In patients with recurrent glioblastoma, the 1-year survival rate was 38.9%, and the median overall survival was 10.2 months. CONCLUSIONS: The results suggest no new safety concerns, and the effectiveness might be similar to previously reported data in clinical trials. Therefore, bevacizumab is considered as one of the treatment options for patients with malignant glioma in real-world clinical practice.

Conflicting Roles of Connexin43 in Tumor Invasion and Growth in the Central Nervous System.

The tumor microenvironment is known to have increased levels of cytokines and metabolites, such as glutamate, due to their release from the surrounding cells. A normal cell around the tumor that responds to the inflammatory environment is likely to be subsequently altered. We discuss how these abnormalities will support tumor survival via the actions of gap junctions (GJs) and hemichannels (HCs) which are composed of hexamer of connexin43 (Cx43) protein. In particular, we discuss how GJ intercellular communication (GJIC) in glioma cells, the primary brain tumor, is a regulatory factor and its attenuation leads to tumor invasion. In contrast, the astrocytes, which are normal cells around the glioma, are "hijacked" by tumor cells, either by receiving the transmission of malignant substances from the cancer cells via GJIC, or perhaps via astrocytic HC activity through the paracrine signaling which enable the delivery of these substances to the distal astrocytes. This astrocytic signaling would promote tumor expansion in the brain. In addition, brain metastasis from peripheral tissues has also been known to be facilitated by GJs formed between cerebral vascular endothelial cells and cancer cells. Astrocytes and microglia are generally thought to eliminate cancer cells at the blood-brain barrier. In contrast, some reports suggest they facilitate tumor progression as tumor cells take advantage of the normal functions of astrocytes that support the survival of the neurons by exchanging nutrients and metabolites. In summary, GJIC is essential for the normal physiological function of growth and allowing the diffusion of physiological substances. Therefore, whether GJIC is cancer promoting or suppressing may be dependent on what permeates through GJs, when it is active, and to which cells. The nature of GJs, which has been ambiguous in brain tumor progression, needs to be revisited and understood together with new findings on Cx proteins and HC activities.

Connexin 43 enhances Bax activation via JNK activation in sunitinib-induced apoptosis in mesothelioma cells.

The constituent protein of gap junctions, connexin (Cx), interacts with various proteins via its C-terminus region, including kinases, cell-adhesion proteins, and a pro-apoptotic protein, Bax. This molecular interaction may affect expression and functioning of the interacting proteins and modulate the cellular physiology. In our previous work, Cx43 was found to interact directly with Bax and in the presence of sunitinib, lead to the Bax-mediated apoptosis in mesothelioma cells. In this study, we investigated the mechanism of how Cx43 promotes Bax-mediated apoptosis using the same cell line. Treatment with sunitinib increased the expression of the active conformation of the Bax protein, which was predominantly localized at the mitochondria, only in Cx43-transfected cells. Bax oligomerization and decrease in the mitochondrial membrane potential were also observed. The involvement of c-Jun N-terminal kinase (JNK) in the interaction of Cx43 and Bax was further examined. Treatment with sunitinib increased the expression of phosphorylated (active) form of JNK only in the Cx43-transfected cells. Phosphorylated JNK and active Bax were co-localized, and the co-localization was suppressed by the knockdown of Cx43. Moreover, JNK inhibition clearly suppressed Bax activation. In conclusion, we identified a novel Cx43-JNK-Bax axis regulating the process of apoptosis for the first time.

Bevacizumab for non-small-cell lung cancer: A nested case control study of risk factors for hemoptysis.

Potentially life-threatening, serious hemoptysis is an adverse event associated with bevacizumab in non-squamous non-small-cell lung cancer (NSCLC) trials. Suggested risk factors include central tumor location and cavitation; however, the profile of hemoptysis occurrence in clinical practice is still unclear. A nested case-control study was conducted to assess the onset profile and risk factors for hemoptysis in bevacizumab-treated patients in a real-world setting in Japan. After bevacizumab was approved for NSCLC, physicians registered all NSCLC patients scheduled for bevacizumab therapy, from November 2009 to August 2011. Patients developing grade 2 hemoptysis requiring an injectable hemostatic agent or grade ≥3 hemoptysis were selected as case subjects, matched with four control subjects each. Case report forms were collected after an observation period of 24 weeks. Radiologists assessed blinded thoracic images. Risk factors for hemoptysis were assessed by univariate and stepwise multivariate analysis. Of 6774 patients registered, 23 (0.3%) experienced grade ≥2 drug-related hemoptysis. A total of 104 patients (21 cases, 83 controls) were analyzed by central reviewers for risk factors of hemoptysis occurrence. In the univariate analysis seven factors were associated with hemoptysis. In the step-wise multivariate analysis, prior thoracic radiotherapy (P = 0.1844), presence of tumor exposure in the central airway (P = 0.0256) and concomitant radiotherapy (P = 0.1169) were identified as risk factors for hemoptysis. While the incidence of hemoptysis was low in the real-world setting in Japan, the three risk factors identified, prior thoracic radiotherapy, presence of tumor exposure in the central airway and concomitant radiotherapy, should be considered when selecting patients for bevacizumab treatment. Although technically classed as a clinical trial, a nested case-control study was a non-interventional surveillance study analyzing all NSCLC patients receiving bevacizumab in Japan, therefore it was not registered as a phase II/III clinical trial would be.

Defective splicing of the background K+ channel K2P5.1 by the pre-mRNA splicing inhibitor, pladienolide B in lectin-activated mouse splenic CD4+ T cells.

The two-pore domain K+ channel K2P5.1 has been implicated in the pathogenesis of autoimmune diseases. We investigated the changes in K2P5.1 activity caused by a defect in normal pre-mRNA splicing in concanavalin A-activated mouse splenic CD4+ T cells. The pre-mRNA splicing inhibitor, pladienolide B (1 µM) markedly decreased full-length K2P5.1 transcription in activated CD4+ T cells, resulting in the disappearance of K2P5.1 activity and an imbalance in Th17 and Treg cytokines. These results suggest that the defect in K2P5.1 splicing by the pre-mRNA splicing inhibitor regulates pro- and/or anti-inflammatory cytokine production in K2P5.1-associated autoimmune diseases.

Safety of Low-Dose Oral Food Challenges for Hen's Eggs, Cow's Milk, and Wheat: Report from a General Hospital without Allergy Specialists in Japan.

An oral food challenge (OFC) is useful for managing food allergies. However, because OFCs have the risk of severe allergic reactions, including anaphylaxis, conducting OFCs under this situation without allergy specialists is difficult. To investigate the safety of a low-dose OFC for eggs, milk, and wheat in a general hospital without allergy specialists. We retrospectively analyzed the medical records of children who were hospitalized in a general hospital without allergy specialists for a low-dose OFC of egg, milk, or wheat between April 2018 and March 2021. The records of 108 patients were evaluated. The median age was 15.8 months (range: 7.5-69.3 months). Challenged foods were eggs (n = 81), milk (n = 23), and wheat (n = 4). Fifty-three (49.0%) patients showed positive allergic reactions. Thirty-five (66.0%) patients showed grade 1 (mild), 18 (34.0%) showed grade 2 (moderate), and none showed grade 3 (severe) reactions. The interventions comprised antihistamines (n = 18), prednisolone (n = 3), inhaled Β2-agonist (n = 2). No patients required adrenaline and no deaths occurred. Low-dose OFCs may be safe in a general hospital without allergy specialists. Conducting a low-dose OFC may be essential in food allergy practice.

Presence and Characteristics of Behavioral and Psychological Symptoms in Subacute Stroke Patients with Cognitive Impairment.

This retrospective cross-sectional study is aimed at investigating the prevalence and characteristics of behavioral and psychological symptoms (BPS) in subacute stroke patients with cognitive impairment. The Neuropsychiatric Inventory-Questionnaire (NPI-Q) was used to assess BPS. A total of 358 consecutive patients with first-ever stroke admitted to rehabilitation wards and with Mini-Mental State Examination (MMSE) scores < 24 on admission were included. BPS was defined as a total NPI-Q Severity or Distress score ≥ 1. Differences between the severity and presence of BPS among patients with severe cognitive impairment (MMSE scores 0-17) and those with mild cognitive impairment (MMSE scores 18-23) were analyzed using the Mann-Whitney U test and chi-squared test, respectively. Eighty-one patients (mean (standard deviation) age, 73.5 (13.1) years) were enrolled for analysis. BPS were observed in 69.1% and 74.1% of patients when assessed with NPI-Q Severity and NPI-Q Distress, respectively. The most frequently observed BPS was apathy, followed by depression (approximately 44% and 40%, respectively). The severity and frequency of delusions, euphoria, apathy, and disinhibition were significantly higher in the severe cognitive impairment group than in the mild cognitive impairment group. However, the severity, distress, and frequency of depression were not dependent on the severity of cognitive impairment. The presence of BPS, especially apathy and depression, in subacute stroke patients with cognitive impairment is high. The severity and frequency of some BPS are higher in patients with severe cognitive impairment than in those with mild cognitive impairment. However, depression is highly prevalent among the patients regardless of the severity of cognitive impairment.

Resting-state functional connectivity disruption between the left and right pallidum as a biomarker for subthreshold depression.

Although the identification of late adolescents with subthreshold depression (StD) may provide a basis for developing effective interventions that could lead to a reduction in the prevalence of StD and prevent the development of major depressive disorder, knowledge about the neural basis of StD remains limited. The purpose of this study was to develop a generalizable classifier for StD and to shed light on the underlying neural mechanisms of StD in late adolescents. Resting-state functional magnetic resonance imaging data of 91 individuals (30 StD subjects, 61 healthy controls) were included to build an StD classifier, and eight functional connections were selected by using the combination of two machine learning algorithms. We applied this biomarker to an independent cohort (n = 43) and confirmed that it showed generalization performance (area under the curve = 0.84/0.75 for the training/test datasets). Moreover, the most important functional connection was between the left and right pallidum, which may be related to clinically important dysfunctions in subjects with StD such as anhedonia and hyposensitivity to rewards. Investigation of whether modulation of the identified functional connections can be an effective treatment for StD may be an important topic of future research.

Comparison of gelatin and low-molecular weight gelatin hydrolysate ingestion on hydroxyproline (Hyp), Pro-Hyp and Hyp-Gly concentrations in human blood.

This study showed that gelatin ingestion significantly increased prolyl-hydroxyproline (Pro-Hyp) levels in plasma of 9 subjects, with maximum concentrations of 15.5 ± 3.0 nmol/mL 2 h post-ingestion. Hydroxyprolyl-glycine (Hyp-Gly) concentrations were significantly increased and reached a maximal level of 2.3 ± 0.5 nmol/mL 1 h post-ingestion of gelatin. A low molecular weight gelatin hydrolysate (LMW-GH) significantly enhanced concentrations of both peptides, while gelatin hydrolysate ingestion did not significantly enhance the maximum concentration and area under the plasma concentration-time curve (AUC) of Hyp-Gly relative to gelatin. The absorption of free Hyp following gelatin ingestion (94.4 ± 16.4 nmol/mL) was significantly lower relative to GH (150.9 ± 15.3 nmol/mL) and LMW-GH (169.1 ± 32.5 nmol/mL). The present study is the first report demonstrating that Hyp-containing peptides are elevated to µM levels in human plasma after gelatin ingestion. These results suggested that gelatin is useful as a functional food as effectively as GH.

Decreased physical activity with subjective pleasure is associated with avoidance behaviors.

The main hypothesis for the relation between physical activity and mental health is that autonomous motivation, such as subjective pleasure for the activity, plays an important role. However, no report has described empirical research designed to examine the role of subjective pleasure in the relation between objectively measured physical activity and psychological indexes. We used accelerometers to collect data indicating participants' physical activity intensity during a week. Participants recorded their subjective pleasure of activity per hour. In 69% of them, the individual correlation coefficients between physical activity and pleasure in an hour (an index of Physical Activity-Pleasure; PA-PL) were positive (r = 0.22, 95%Cl = [0.11-0.38]), indicating that pleasant sensations increased concomitantly with increasing physical activity. Conversely, 31% participants exhibited negative values of PA-PL, which means that the increase in physical activity had the opposite effect, decreasing pleasure. Multiple linear regression analysis showed that avoidance/rumination behaviors decreased significantly with increased PA-PL (ß = -6.82, 95%CI: [-13.27 to -0.38], p < .05). These results indicate that subjective pleasure attached to the PA is more important than the PA amount for reducing depressive behavior.

Synthesis of 4-Imidazolidinones from Diamides and Ethynyl Benziodoxolones via Double Michael-Type Addition: Ethynyl Benziodoxolones as Electrophilic Ynol Synthons.

The moiety of 4-imidazolidinone is an important structural motif in organic synthesis and medicinal chemistry. We present the synthesis of 4-imidazolidinones from various diamides with ethynyl benziodoxolones through double Michael-type addition, which is an unprecedented reaction mode for hypervalent alkynyl iodine compounds. cis-2,5-Disubstituted 4-imidazolidinones were diastereoselectively synthesized from amino acid derived diamides. Having derivatized the 4-imidazolidinones, several control experiments and density functional theory calculations were conducted to realize mechanistic insight.

Vitality index is a predictor of the improvement in the functional independence measure score in subacute stroke patients with cognitive impairment.

OBJECTIVES: To investigate the effect of motivation on improvements in the Functional Independence Measure (FIM) scores in subacute stroke patients with cognitive impairment. METHODS: This retrospective cohort study included 358 consecutive subacute stroke patients with first-ever stroke and Mini-Mental State Examination score ≤23 at admission. We determined motivation and rehabilitation outcome using the vitality index and FIM-motor gain, respectively. Stepwise multiple regression analysis was performed to identify the factors at admission related to FIM-motor gain. RESULTS: Of 80 participants enrolled in this study (mean age: 74.2 ± 11.3 years). The median (interquartile range) vitality index at admission and FIM-motor gain were 7 (4) and 23 (22) points, respectively. Stepwise multiple regression analysis revealed that age (B, -0.43; 95% confidence interval [CI], -0.65-(-0.21); ß, -0.31; P <.001), duration from stroke onset to admission (B, -0.18; 95% CI, -0.33-(-0.04); ß, -0.20; P =.014) and Stroke Impairment Assessment Set-motor function (B, 1.27; 95% CI, 0.92-1.61; ß, 0.78; P <.001), FIM-motor (B, -0.80; 95% CI, -1.01-(-0.60); ß, -0.95; P <.001), and vitality index (B, 3.79; 95% CI, 2.37-5.21; ß, 0.50; P <.001) scores at admission were significantly associated with the FIM-motor gain. DISCUSSION: The vitality index was significantly associated with FIM improvement in subacute stroke patients with cognitive impairment.

Transformation of Acute Myeloid Leukemia with Deletion of Chromosome 7q and Additional Abnormalities in Chromosome 8 in a Patient with Essential Thrombocythemia.

This is a case report of a 60-year-old male patient with essential thrombocythemia (ET) that progressed to acute myeloid leukemia (AML) in approximately 9 years. His platelet count decreased approximately 8 years after ET treatment with hydroxyurea (HU) and aspirin. The dose of HU was reduced because of suspected myelosuppression due to HU; however, myelosuppression did not improve. Bone marrow examination revealed myelofibrosis; therefore, ruxolitinib was administered. Approximately 1 year later, his leukocyte and blast counts in the peripheral blood increased; thus, ET was judged to have progressed to AML-myelodysplasia-related change. Induction chemotherapy and consolidation therapy were initiated; however, the patient unfortunately failed to achieve complete remission. We then continued to administer salvage chemotherapy; however, his general condition worsened, and he died from cerebral hemorrhage. The karyotype at the onset of ET was 46,XY, which changed to 47,XY,del(7q),+8 at the time of AML diagnosis. In addition, genetic testing revealed FLT-3 ITD mutation. His histopathological analysis showed subarachnoid and intraparenchymal hemorrhages and tumor cell infiltration into the cerebrum, brainstem, and cerebellum. In this case, deletion of the long arm of chromosome 7, additional abnormalities in chromosome 8, and FLT3-ITD mutation were confirmed as risk factors for having developed secondary AML for approximately 9 years and death from cerebral hemorrhage 1 year later.

Severe Gastroparesis After Ablation for Atrial Fibrillation.

A 70-year-old man was treated with catheter ablation for symptomatic paroxysmal atrial fibrillation (AF). The treatment consisted of pulmonary vein isolation and radiofrequency ablation of the cavo-tricuspid isthmus line. However, the patient started vomiting two days after ablation. Abdominal radiography and plain abdominal computed tomography revealed gastric distension and massive accumulation of food residues. Esophagogastroduodenoscopy after fasting for two days revealed no organic stricture; food residues were retained in the stomach but not in the duodenum, suggesting gastroparesis. The most likely mechanism underlying gastroparesis associated with AF ablation is collateral periesophageal vagal nerve injury. Mosapride citrate is considered effective for symptoms.