Haematopoietic regeneration by HLA-A*0206-deficient clones in severe aplastic anaemia without definitive immunosuppressive treatment.

We describe the case of a 74-year-old man with severe aplastic anaemia who experienced persistent remission attributed to proliferation of HLA allele-deficient clones. Despite an initial worsening of pancytopenia with eltrombopag and ciclosporin treatment, gradual trilineage haematopoietic recovery occurred, with blood counts normalizing over 3 years. Flow cytometry and deep nucleotide sequencing revealed that haematopoiesis was primarily supported by several clones with somatic mutations that inactivated antigen presentation via HLA-A*0206. This suggests that monitoring haematopoietic regeneration by immune escape clones could be an alternative approach for immune aplastic anaemia patients who possess HLA allele-deficient clones and cannot tolerate standard therapy.

Application of transition-edge sensors for micro-X-ray fluorescence measurements and micro-X-ray absorption near edge structure spectroscopy: a case study of uranium speciation in biotite obtained from a uranium mine.

In this study, we successfully applied a transition-edge sensor (TES) spectrometer as a detector for microbeam X-ray measurements from a synchrotron X-ray light source in the hard X-ray region to determine uranium (U) distribution at the micro-scale and its chemical species in biotite obtained from a U mine. It is difficult to separate the fluorescent X-ray of the U Lα1 line at 13.615 keV from that of the Rb Kα line at 13.395 keV in the X-ray fluorescence spectrum with an energy resolution of approximately 220 eV using a conventional silicon drift detector (SDD). Meanwhile, the fluorescent X-rays of U Lα1 and Rb Kα were fully separated by a TES with 50 eV energy resolution at an energy of around 13 keV. The successful peak separation by the TES led to an accurate mapping analysis of trace U in micro-X-ray fluorescence measurements and a decrease in the signal-to-background ratio in micro-X-ray absorption near edge structure spectroscopy. Thus, it could be a powerful tool for studying the U distribution and speciation in various environmental samples.

How We Interpret Thrombosis with Thrombocytopenia Syndrome?

Platelets play an important role in hemostasis, and a low platelet count usually increases the risk of bleeding. Conditions in which thrombosis occurs despite low platelet counts are referred to as thrombosis with thrombocytopenia syndrome, including heparin-induced thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia, paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, thrombotic microangiopathy (TMA), and disseminated intravascular coagulation. TMA includes thrombotic thrombocytopenic purpura, Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (HUS), and atypical HUS. Patients with these pathologies present with thrombosis and consumptive thrombocytopenia associated with the activation of platelets and the coagulation system. Treatment varies from disease to disease, and many diseases have direct impacts on mortality and organ prognosis if therapeutic interventions are not promptly implemented. Underlying diseases and the results of physical examinations and general laboratory tests as part of a thorough workup for patients should promptly lead to therapeutic intervention before definitive diagnosis. For some diseases, the diagnosis and initial treatment must proceed in parallel. Utilization of not only laboratory tests but also various scoring systems is important for validating therapeutic interventions based on clinical information.

Left atrial epicardial adipose tissue exacerbates electrical conduction disturbance in normal-weight patients undergoing pulmonary vein isolation for atrial fibrillation.

INTRODUCTION: Epicardial adipose tissue (EAT) exacerbates both electrical and structural remodeling in obese atrial fibrillation (AF) patients, but the impacts of EAT on atrial arrhythmogenicity remain unclear in normal-weight AF patients. Therefore, we sought to investigate this issue using electroanatomic mapping. METHODS AND RESULTS: We enrolled drug-refractory 105 paroxysmal AF patients in the normal body mass index range (18.5-24.9 kg/m2 ), who had undergone electroanatomic mapping after pulmonary vein isolation (PVI). One day before PVI, we assessed P-wave duration in a 12-lead electrocardiogram and left atrial (LA)-EAT volumes using contrast-enhanced computed tomography. The patients were divided into two groups based on the median LA-EAT volume (16.0 ml); the high LA-EAT group (≥16.0 ml, n = 53) and low LA-EAT group (<16.0 ml, n = 52). We compared P-wave duration, LA conduction velocity and bipolar voltage, the presence of low-voltage zone (<0.5 mV), and LA volume index on echocardiography between the two groups. The LA bipolar voltage, low-voltage zone, and LA volume index were not different between the high and low LA-EAT groups. However, P-wave duration was significantly longer in the high group than in the low group (p < .001). Additionally, the LA conduction velocity was significantly more depressed in the high group than in the low group (p < .001). Multivariate linear regression analysis revealed that LA-EAT volume was correlated with P-wave duration (ß = .367, p < .001) and conduction velocity (ß = -.566, p < .001), respectively. CONCLUSIONS: Increased LA-EAT volumes were associated with electrical conduction disturbance after PVI in normal-weight patients with AF. P-wave duration may be a clinically useful predictor of LA-EAT.

Utility of short-time electrocardiogram to assess risk for atrial arrhythmia recurrence: Impact of atrial premature beat occurrence 1 day after pulmonary vein isolation for atrial fibrillation.

INTRODUCTION: Atrial premature beats (APBs) are the trigger for atrial fibrillation (AF). We sought to investigate the clinical significance of APB occurrence 1 day after pulmonary vein isolation (PVI) for AF using a short-time electrocardiogram. METHODS: A total of 206 patients undergoing PVI for paroxysmal AF were included. Electrocardiogram recording for 100 consecutive beats was performed 1 day after PVI. The patients were divided into two groups: those with reproducible APBs (≥1 beat) during reassessment (APB group, n = 49) or those without (non-APB group, n = 157). Late recurrence was defined as atrial tachyarrhythmia recurrence 3-12 months after PVI. The impact of APB occurrence on outcomes was investigated. RESULTS: Late recurrence occurred in 19 patients (9.2%). The presence of low-voltage areas, left atrial volume, and recurrence rate were higher in the APB group than in the non-APB group. In the APB group, the patients with recurrence had lower prematurity index (PI, coupling interval of APB/previous cycle length) compared to those without. Receiver-operating characteristic analysis revealed PI (<59.3) to be a predictive factor of recurrence (area under the curve: 0.733). The study subjects were then reclassified into three groups according to the absence of APB occurrence (n = 157), presence thereof with PI ≥ 59.3 (n = 33), and presence with PI < 59.3 (n = 16). The multivariate Cox models revealed that APB with PI < 59.3 was an independent predictor for recurrence (hazard ratio, 8.735; p < 0.001). CONCLUSION: A short-time electrocardiogram enables risk assessment for arrhythmia recurrence, and APB with low PI 1 day after PVI is a powerful predictor.

Clinical Outcomes of Follow-Up Observation After Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma Invading the Muscularis Mucosa Without Lymphovascular Involvement.

BACKGROUND: The therapeutic approach after endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) diagnosed as pathological T1a-muscularis mucosa (pT1a-MM) without lymphovascular involvement (LVI) remains uncertain. We aimed to determine whether observation after ESD is acceptable for patients without LVI showing pT1a-MM cancer. METHODS: We retrospectively registered 566 ESCC patients who were treated with ESD at ten institutions between January 2007 and December 2015. Of those, 447 cases showing pT1a-epithelium/lamina propria mucosa (EP/LPM) without LVI and vertical margin (VM) (EP/LPM group), and 41 cases showing pT1a-MM without LVI and VM (MM group) were analyzed in this investigation. The clinical outcomes were assessed between the groups. RESULTS: The 5 year cumulative incidence of metastatic recurrence was 0.5% and 3.3% in the EP/LPM and MM groups, respectively (P = 0.121). Two cases showing pT1a-EP/LPM and one showing pT1a-MM experienced lymph node recurrence. The 5 year cumulative incidence of local recurrence was 1.5% and 3.8% in the EP/LPM and MM groups, respectively (P = 0.455). The 5 year disease-specific survival (DSS) rate was 99.3% and 96.6% in the EP/LPM and MM groups, respectively (P = 0.118), whereas the 5 year overall survival rate was significantly higher in the EP/LPM group than in the MM group (92.6% versus 81.1%, respectively; P = 0.021). CONCLUSIONS: As regards metastatic recurrence and DSS, ESCC patients with pT1a-MM without LVI showed favorable outcomes that were equivalent to those with pT1a-EP/LPM, even when they were not treated with additional therapy after ESD.

Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development.

At the end of 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) was detected in Wuhan, China, that spread rapidly around the world, with severe consequences for human health and the global economy. Here, we assessed the replicative ability and pathogenesis of SARS-CoV-2 isolates in Syrian hamsters. SARS-CoV-2 isolates replicated efficiently in the lungs of hamsters, causing severe pathological lung lesions following intranasal infection. In addition, microcomputed tomographic imaging revealed severe lung injury that shared characteristics with SARS-CoV-2-infected human lung, including severe, bilateral, peripherally distributed, multilobular ground glass opacity, and regions of lung consolidation. SARS-CoV-2-infected hamsters mounted neutralizing antibody responses and were protected against subsequent rechallenge with SARS-CoV-2. Moreover, passive transfer of convalescent serum to naïve hamsters efficiently suppressed the replication of the virus in the lungs even when the serum was administrated 2 d postinfection of the serum-treated hamsters. Collectively, these findings demonstrate that this Syrian hamster model will be useful for understanding SARS-CoV-2 pathogenesis and testing vaccines and antiviral drugs.

Risk and prognostic factors of invasive gastric cancer detection during surveillance endoscopy: Multi-institutional cross-sectional study.

OBJECTIVES: Esophagogastroduodenoscopy (EGD) is important for the detection of curable gastric cancer (GC). However, there are no appropriate surveillance data during routine endoscopic inspections. This study aimed to clarify the risk factors of pT1b or deeper GC detection during surveillance endoscopy. METHODS: This was a retrospective, multicenter, cross-sectional study conducted in 15 Japanese hospitals. We retrospectively analyzed patients with GC who had previously undergone surveillance endoscopy at each institution from January 2014 to March 2020. Patients who had undergone gastrectomy, non-infection of Helicobacter pylori (Hp), and those with intervals <3 months or >10 years from a previous endoscopy were excluded. RESULTS: In total, 1085 patients with GCs detected during surveillance endoscopy were enrolled. The multivariate logistic analysis revealed that current Hp infection (odds ratio [OR] 2.18; 95% confidence interval [CI] 1.50-3.16) and a surveillance interval of >1.5 years (OR 1.96; 95% CI 1.35-2.84) were independent risk factors for pT1b or deeper GC. The 5-year disease-specific survival (5y-DSS) rate of GC was significantly lower in patients with surveillance interval of >1.5 years than in those with surveillance interval of ≤1.5 years (93.7% vs. 98.3%, P < 0.001). Similarly, the 5y-DSS rate of GC was significantly lower in patients with active Hp infection than in those without (93.7% vs. 99.4%, P < 0.001). CONCLUSION: In this study, a surveillance interval of >1.5 years and current Hp infection were independent risk factors for detecting pT1b or deeper GC. Additionally, these factors were poor prognostic factors of the detected GC during surveillance endoscopy.

Procedural characteristics of pulmonary vein isolation with high-power short-duration setting compared to conventional setting.

PURPOSE: The purpose of this study was to investigate the safety and efficacy of high-power short-duration (HP-SD) ablation compared to conventional ablation in patients with atrial fibrillation (AF). METHODS: We enrolled consecutive 158 drug-refractory symptomatic AF patients (119 males, mean age 63 ± 10 years) who had undergone first radiofrequency pulmonary vein isolation (PVI). PVI was performed using the conventional setting (20-35 W) in 73 patients (Conventional group) and using the HP-SD setting (45-50 W) in 85 patients (HP-SD group). The rate of first pass isolation, remaining gaps after circumferential ablation, dormant conduction, and the radiofrequency application time in each pulmonary vein (PV) were compared between the groups. RESULTS: The first pass isolation ratio was significantly higher in the HP-SD group than in the Conventional group (81% vs. 65%, P = 0.027) in the right PV, but did not differ in the left PV. The remaining gaps were fewer in the right superior PV (4% vs. 21%, P = 0.001) and left inferior PV (1% vs. 8%, P = 0.032) areas, and the radiofrequency application time in each PV was shorter (right PV, 12.0 ± 8.9 min vs. 34.0 ± 31.7 min, P < 0.001; left PV, 10.6 ± 3.6 min vs. 25.7 ± 22.3 min, P < 0.001) in the HP-SD group than in the Conventional group. CONCLUSION: The use of the HP-SD setting might contribute to improve the first pass isolation rate and to shorten the radiofrequency application time in each PV.

Endoscopic Submucosal Dissection for Early Gastric Cancer in Patients Aged 85 Years Old or Older Is Associated with a Good Prognosis Compared to Conservative Treatment without Any Invasive Procedure.

INTRODUCTION: Studies have reported the feasibility of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in elderly people with respect to both short- and long-term outcomes. As the elderly population in society increases, the requirement for managing super-elderly patients aged ≥85 years with EGC will also increase. This study aims to identify the long-term clinical outcomes of ESD for clinical T1N0 EGC in patients aged ≥85 years. METHODS: A total of 370 consecutive patients aged ≥85 years with clinical T1N0 EGC who were managed in 11 institutions were reviewed retrospectively. On the basis of treatment strategy, we compared the overall survival (OS) and disease-specific survival (DSS) after performing propensity score-matched analysis between patients undergoing ESD (ESD group) and those not undergoing treatment (conservative treatment group). The potential prognostic factors were also investigated in the propensity score-matched patients. RESULTS: After propensity score matching, we found that the 3-year OS and DSS rates were significantly higher in the ESD group than in the conservative treatment group (OS, 82.2% vs. 50.5%; p < 0.001; DSS, 100% vs. 80.1%; p = 0.008). Furthermore, ESD was identified as a significant factor for prolonged OS, whereas Charlson comorbidity index (CCI) ≥3 and prognostic nutritional index (PNI) <36.2 were associated with reduced OS. CONCLUSION: ESD was associated with improved OS in patients with clinical T1N0 EGC aged ≥85 years compared with the absence of treatment. Furthermore, CCI and PNI were helpful for patient selection.

Prognostic risk factors associated with esophageal squamous cell carcinoma patients undergoing endoscopic submucosal dissection: a multi-center cohort study.

BACKGROUND: Long-term outcomes of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) have not been assessed in a large, multicenter cohort. We aimed to evaluate long-term outcomes of ESD for ESCC in a real-world setting. METHODS: We retrospectively recruited 659 patients who underwent ESD for ESCC at ten institutions from January 2007 to December 2015. Of these, 566 patients were analyzed and classified into three groups according to the pathologic invasion depth after ESD: epithelium/lamina propria mucosa (EP/LPM group: 454 patients), muscularis mucosa/submucosa invasion ≤ 200 µm below the inferior margin of the muscularis mucosa (MM/SM1 group: 81 patients), and submucosa invasion > 200 µm below the MM inferior margin (SM2 group: 31 patients). RESULTS: The 5-year overall survival rates in the EP/LPM, MM/SM1, and SM2 groups were 92.6%, 80.0%, and 62.7%, respectively, while the 5-year disease-specific survival rates were 99.7%, 96.9%, and 88.3%, respectively. Multivariate analyses revealed that the invasion depth, Charlson Comorbidity Index (CCI), and prognostic nutritional index (PNI) were independent prognostic factors. Hazard ratios in the MM/SM1 and SM2 groups were 2.25 (95% confidence interval [CI] 1.04-4.83; P = 0.038) and 3.18 (95% CI 1.08-9.34; P = 0.036), respectively, compared to those in the EP/LPM group, while those for patients with a CCI ≥ 3 and PNI ≤ 47.75 were 3.25 (95% CI 1.79-5.89; P < 0.001) and 2.42 (95% CI 1.26-4.65; P = 0.008), respectively. CONCLUSIONS: This study identified that invasion depth, presence of comorbid diseases and preoperative nutritional status are independent prognostic risk factors associated with ESCC patients undergoing ESD.

Optimal surveillance interval after piecemeal endoscopic mucosal resection for large colorectal neoplasia: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Colorectal neoplastic lesions (≥ 20 mm) are commonly treated via piecemeal endoscopic mucosal resection (p-EMR) but have a high rate of local recurrence. We aimed to clarify the optimal surveillance interval after p-EMR for these neoplasias. METHODS: In this multicenter (15 participating institutions) prospective, randomized trial, 180 patients recruited over a 4-year period and were classified based on tumor location, tumor diameter, histological diagnosis, institution, and number of resected specimens. The patients underwent curative p-EMR followed by scheduled surveillance colonoscopy at 3, 6, 12, and 24 months after p-EMR (group A; n = 90) or at 6, 12, and 24 months after p-EMR (group B; n = 90). The primary endpoint was cumulative local recurrence at 6 months after p-EMR. Secondary endpoints included local recurrence and the cumulative surgical resection rate of recurrent tumors during the 24-month follow-up period. RESULTS: The median tumor diameter was 25 mm (IQR 20-30). Six months after p-EMR, 12 and 6 local recurrences were noted in groups A and B, which corresponded to 13 and 8 recurrences, respectively, during the 24-month surveillance period. The primary and secondary endpoints of recurrence were not significantly different between the groups on either intention-to-treat or per-protocol analysis; no surgery case was observed in group B when a strict surveillance protocol of 6-, 12-, and 24-month follow-up post-EMR was followed. CONCLUSIONS: For patients who underwent p-EMR for neoplastic lesions, additional postprocedural 3-month surveillance did not show superior results in detecting recurrence compared with a 6-month surveillance interval. CLINICAL TRIAL REGISTRATION: UMIN000015740.

Predictive impacts of chronic kidney disease and cardiac sympathetic nervous activity on lethal arrhythmic events in chronic heart failure.

BACKGROUND: The clinical implications of chronic kidney disease (CKD) and cardiac sympathetic nervous activity (CSNA) regarding lethal arrhythmic events have not yet been fully elucidated in patients with chronic heart failure (CHF). We hypothesized that the combination of CKD and abnormal CSNA, assessed by 123 I-metaiodobenzylguanidine (123 I-MIBG) scintigraphy, may provide useful prognostic information for lethal arrhythmic events. METHODS: We studied 165 consecutive hospitalized CHF patients without dialysis. Cardiac 123 I-MIBG scintigraphy was performed in a clinically stable condition, and abnormal CSNA was defined as a late heart-to-mediastinum ratio of <1.6. CKD was defined as an estimated glomerular filtration rate of <60 ml/min/1.73 m2 . We then investigated the incidence of lethal arrhythmic events (sustained ventricular tachyarrhythmia, appropriate implantable cardioverter-defibrillator therapy, or sudden cardiac death). RESULTS: During a median follow-up of 5.3 years, lethal arrhythmic events were observed in 40 patients (24.2%). The patients were divided into four groups according to the presence of CKD and CSNA abnormality: non-CKD/normal CSNA (n = 52), CKD/normal CSNA (n = 39), non-CKD/abnormal CSNA (n = 33), and CKD/abnormal CSNA (n = 41). Kaplan-Meier analysis showed that CKD/abnormal CSNA had the highest event rate (log-rank p = .004). Additionally, the Cox proportional hazard analysis revealed that CKD/abnormal CSNA was a predictor for lethal arrhythmic events compared with non-CKD/normal CSNA (hazard ratio, 5.368, p = .001). However, the other two groups did not show significant differences compared with the non-CKD/normal CSNA group. CONCLUSIONS: The combination of CKD and abnormal CSNA, assessed by 123 I-MIBG scintigraphy, had a high predictive value for lethal arrhythmic events in patients with CHF.

The Impact of Tofogliflozin on Physiological and Hormonal Function, Serum Electrolytes, and Cardiac Diastolic Function in Elderly Japanese Patients with Type 2 Diabetes Mellitus.

The sodium glucose transporter 2 (SGLT2) inhibitor tofogliflozin is a glucose-lowering drug that causes the excretion of surplus glucose by inhibiting SGLT2. Because of tofogliflozin's osmotic diuresis mechanism, patients' serum electrolytes, body fluid levels, and cardiac function must be monitored. We retrospectively analyzed the cases of 64 elderly Japanese patients with type 2 diabetes mellitus (T2DM) who received tofogliflozin for 3 months. Their HbA1c, serum electrolytes (sodium, potassium, chloride), hematocrit, brain natriuretic peptide (cardiac volume load marker) and renin and aldosterone (RAA; an index of regulatory hormones involved in body fluid retention) were continuously monitored during the investigation period. Renal function and cardiac function (by echocardiography) were assessed throughout the period. HbA1c significantly decreased (ß1=-0.341, p<0.0001, linear regression analysis [LRA]). Most of the hormonal, electrolyte, and physiological parameters were maintained throughout the study period. In these circumstances, E/e' tended to decrease (ß1=-0.382, p=0.13, LRA). Compared to the baseline, E/e' was significantly decreased at 1 and 3 months (p<0.01, p<0.05). In the higher E/e' group (E/e'≥10, n=34), E/e' decreased significantly (ß1=-0.63, p<0.05, LRA). ΔE/e' was correlated with body-weight change during treatment (r=0.64, p<0.01). The 3-month tofogliflozin treatment improved glycemic control and diastolic function represented by E/e' in T2DM patients, without affecting serum electrolytes, renal function, or RAA. No negative impacts on the patients were observed. Three-month tofogliflozin treatment lowered glucose and improved cardiac diastolic function.

Therapeutic Strategies for Disseminated Intravascular Coagulation Associated with Aortic Aneurysm.

Aortic aneurysms are sometimes associated with enhanced-fibrinolytic-type disseminated intravascular coagulation (DIC). In enhanced-fibrinolytic-type DIC, both coagulation and fibrinolysis are markedly activated. Typical cases show decreased platelet counts and fibrinogen levels, increased concentrations of fibrin/fibrinogen degradation products (FDP) and D-dimer, and increased FDP/D-dimer ratios. Thrombin-antithrombin complex or prothrombin fragment 1 + 2, as markers of coagulation activation, and plasmin-α2 plasmin inhibitor complex, a marker of fibrinolytic activation, are all markedly increased. Prolongation of prothrombin time (PT) is not so obvious, and the activated partial thromboplastin time (APTT) is rather shortened in some cases. As a result, DIC can be neither diagnosed nor excluded based on PT and APTT alone. Many of the factors involved in coagulation and fibrinolysis activation are serine proteases. Treatment of enhanced-fibrinolytic-type DIC requires consideration of how to control the function of these serine proteases. The cornerstone of DIC treatment is treatment of the underlying pathology. However, in some cases surgery is either not possible or exacerbates the DIC associated with aortic aneurysm. In such cases, pharmacotherapy becomes even more important. Unfractionated heparin, other heparins, synthetic protease inhibitors, recombinant thrombomodulin, and direct oral anticoagulants (DOACs) are agents that inhibit serine proteases, and all are effective against DIC. Inhibition of activated coagulation factors by anticoagulants is key to the treatment of DIC. Among them, DOACs can be taken orally and is useful for outpatient treatment. Combination therapy of heparin and nafamostat allows fine-adjustment of anticoagulant and antifibrinolytic effects. While warfarin is an anticoagulant, this agent is ineffective in the treatment of DIC because it inhibits the production of coagulation factors as substrates without inhibiting activated coagulation factors. In addition, monotherapy using tranexamic acid in cases of enhanced-fibrinolytic-type DIC may induce fatal thrombosis. If tranexamic acid is needed for DIC, combination with anticoagulant therapy is of critical importance.

Coagulopathy and Fibrinolytic Pathophysiology in COVID-19 and SARS-CoV-2 Vaccination.

Coronavirus Disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is frequently complicated by thrombosis. In some cases of severe COVID-19, fibrinolysis may be markedly enhanced within a few days, resulting in fatal bleeding. In the treatment of COVID-19, attention should be paid to both coagulation activation and fibrinolytic activation. Various thromboses are known to occur after vaccination with SARS-CoV-2 vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can occur after adenovirus-vectored vaccination, and is characterized by the detection of anti-platelet factor 4 antibodies by enzyme-linked immunosorbent assay and thrombosis in unusual locations such as cerebral venous sinuses and visceral veins. Treatment comprises high-dose immunoglobulin, argatroban, and fondaparinux. Some VITT cases show marked decreases in fibrinogen and platelets and marked increases in D-dimer, suggesting the presence of enhanced-fibrinolytic-type disseminated intravascular coagulation with a high risk of bleeding. In the treatment of VITT, evaluation of both coagulation activation and fibrinolytic activation is important, adjusting treatments accordingly to improve outcomes.

[Improving outcome of COVID-19-associated thrombosis: the need for evaluation of fibrinolytic activation].

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 and is known to have thrombotic complications. Various-sized thrombosis occurs in the arteries and veins, especially in lung tissue. The prevention and treatment of thrombosis is an important issue that is directly linked to its prognosis. Additionally, the drastic fibrinolytic enhancement and lethal bleeding in some severe COVID-19 are important issues. The efficacy of antiplatelet for COVID-19 is controversial. Thus, warfarin or tranexamic acid alone should be avoided. Heparin is effective for mild to moderate COVID-19 but is ineffective in severe cases since the anticoagulant activity of heparin is insufficient or heparin increases major bleeding. In severe COVID-19 cases with drastic fibrinolytic enhancement, heparin and nafamostat combination therapy may avoid lethal bleeding. In COVID-19 clinical practice, not only the coagulation activation was evaluated but also the fibrinolytic activation to consider treatment strategies.

How Grief, Funerals, and Poverty Affect Bereaved Health, Productivity, and Medical Dependence in Japan.

Grief has been shown to weaken bereaved persons' health, but measurements of their lost time and medical expense remain rare. Funerals traditionally managed and assuaged grief through ritual expression, approval, and social support. Research suggests that satisfying funeral participation reduces grief, while poverty exacerbates it. We hypothesized that: (1) psycho-physical symptoms of grief, (2) abbreviation/dissatisfaction in the funeral, and (3) poverty, correlate with decreased productivity and increased medical and social services use. We collected data from 165 mourning families about their grief, funerals, and subsequent medical conditions. (1) Deeper grief after bereavement in Japan correlated with more physical problems, more down time, and more medical dependency. (2) Low satisfaction with funerals correlated with higher hospital, pharmacy, and counseling costs. (3) Low income families lost more time, while declining incomes showed increased pharmaceutical costs. This suggests that satisfying funerals and income safeguards may reduce costs of low productivity and increased public services dependency.

Evaluations of Funerals and Health Trajectories in the Second Year After Bereavement-The Ongoing Japan National Survey.

Our nationwide postal survey analyzing 190 responses from Japanese bereaved who had responded a year earlier found that funeral dissatisfaction rose during the second year after the funeral. Controverting previous research advocating participation in funeral planning, elderly bereaved spouses forced to decide about and/or pay for the funeral showed elevated grief as much as 2 years later. While not reaching levels diagnosed as prolonged, traumatic, or complicated grief, nevertheless one out of three of our bereaved sample showed continuing daily symptoms of grief from 14 to 24 months after their bereavement, with continued or increasing use of tranquillizers or antidepressants. The medical and pharmaceutical costs incurred by mourners more than a year after bereavement warrant further research into what factors improve or exacerbate the health of grieving bereaved, not limited to a single year after the bereavement.

Clinical Outcomes of Vonoprazan-Treated Patients after Endoscopic Submucosal Dissection for Gastric Neoplasms: A Prospective Multicenter Observation Study.

BACKGROUND: Vonoprazan (VPZ) has the potential to prevent delayed bleeding and promote ulcer healing after endoscopic submucosal dissection (ESD) similar to proton pump inhibitors (PPIs). OBJECTIVE: We aimed to evaluate the outcomes of VPZ-treated patients after ESD and compared the efficacy and feasibility in preventing a delayed bleeding and in healing an artificial ulcer after ESD between the VPZ and PPI therapies. METHODS: This was a prospective, observation study in 11 Japanese medical institutions. We enrolled and evaluated 223 patients who underwent gastric ESD followed by VPZ treatment (VPZ group). We selected 385 patients who underwent gastric ESD followed by PPI treatment as historical controls (PPI group) to compare the outcomes between the VPZ and PPI groups using a propensity score matching analysis. RESULTS: Among the 223 patients treated with VPZ, 173 were men and 50 were women with a median age of 72 years and with a median tumor size of 12.0 mm. Rates of en bloc resection and complete resection were 99.1 and 94.2%, respectively. Lymphovascular invasion was found in 6 (6.3%) cases. Intraoperative perforation and delayed bleeding occurred in 3 (1.3%) and 10 patients (4.5%), respectively. Scarring of artificial post-ESD ulcer was found in 153 patients (68.6%) at 6 weeks after ESD. The 205 pairs of propensity score-matched patients were comparable between the VPZ and PPI groups. The rate of delayed bleeding in the VPZ and PPI groups was 3.9 and 4.4%, respectively (difference, 0.5 percentage points; 95% confidence interval, -3.7 to 2.8%; non-inferiority, p = 0.01). Therefore, VPZ therapy demonstrated non-inferiority against PPI therapy in reducing the rate of delayed bleeding. The scar-stage ulcer at 6 weeks in the VPZ group and 8 weeks in the PPI group was 68.3 and 74.6%, respectively (p = 0.19). CONCLUSIONS: VPZ therapy showed an efficacy and feasibility in preventing a delayed bleeding after ESD similar to the PPI therapy. VPZ for 6 weeks and PPI for 8 weeks were similarly effective for an artificial ulcer healing after ESD.