[Acquired thrombotic thrombocytopenic purpura during durvalumab monotherapy for non-small cell lung cancer].

Immune checkpoint inhibitor (ICI)-induced thrombocytopenias are rare immune-related adverse events (irAE), but ICI-related thrombotic thrombocytopenic purpura (TTP) is extremely rare. A 79-year-old woman with non-small cell lung cancer received maintenance therapy with the anti-human PD-L1 monoclonal antibody durvalumab. Four weeks after the last infusion, she developed overt TTP. Remission was achieved by plasma exchange and prednisolone, and the patient has now been recurrence-free for over 12 months. To our knowledge, this is the first report of TTP occurring as an irAE of durvalumab.

Ephedrine Alkaloid-Independent High-Affinity Immunoglobulin-E Receptor (FcεRI) Internalization Results in CCL2 Production without Inducing Mast Cell Degranulation.

Mast cells (MCs) play an important role in allergies, leading to the development of MC-targeted therapies. Ephedra herb (Mao) has potent anti-allergic activity, but contains ephedrine alkaloids (EAs); therefore, its hazardous effects are taken into consideration during its clinical use. We previously reported that Mao attenuates robust MC degranulation by an allergen through high-affinity immunoglobulin E (IgE) receptor (FcεRI) internalization, in which an EA-independent mechanism was suggested to be at play. This study aimed to deepen our understanding of the potential of Mao against FcεRI internalization using two strains with different EA contents. Mao extracts were administered to bone marrow-derived MCs (BMMCs), and their cellular responses, including FcεRI internalization, were analyzed. In addition, physiological events were evaluated using a passive cutaneous anaphylactic (PCA) reaction mouse model. BMMCs mediate the production of diverse inflammatory mediators. Among these, the potent chemokine CCL2 is thought to be differentially regulated from other pro-inflammatory mediators. We found that Mao significantly induces CCL2 expression in BMMCs despite suppressing robust degranulation through FcεRI internalization. Importantly, this was a distinctly EAs-independent response. In the PCA reaction, local MC activation following allergen challenge was suppressed by Mao treatment, which strengthened the view that Mao sufficiently decreased the rapid activation of MCs and promoted CCL2 secretion. Collectively, these observations provide additional insights into the mechanism of Mao-induced silent FcεRI internalization in MCs and the complex and heterogeneous secretory responses operating in MCs.

The association between experience of COVID-19-related discrimination and psychological distress among healthcare workers for six national medical research centers in Japan.

BACKGROUND: Discrimination is an important determinant of negative mental health outcomes. This study determined the association between the experience of COVID-19-related discrimination and psychological distress among healthcare workers (HCWs) in Japan. METHODS: This cross-sectional study conducted a health survey among 5703 HCWs of six national medical and research centers in Japan from October 2020 to March 2021. COVID-19-related discrimination was defined either when participants or their family members were badmouthed or when they felt discriminated against in some way. We used the Kessler Psychological Distress Scale (K6) to assess the presence of severe psychological distress (≥ 13 points). We used logistic regression models to examine the association between discrimination and psychological distress. We also identified factors associated with discrimination. RESULTS: Of the participants, 484 (8.4%) reported COVID-19-related discrimination and 486 (8.5%) had severe psychological distress. HCWs who were female vs. male (adjusted odds ratio [AOR] = 1.41, 95% confidence interval [CI] = 1.28-1.55), had high vs. low viral exposure (AOR = 2.31, 95% CI = 1.81-2.93), and worked for 11 or more hours/day vs. 8 or less hours/day (AOR = 1.42, 95% CI = 1.35-1.49) were more likely to have experienced COVID-19-related discrimination. The AOR (95% CI) of severe psychological distress was 1.83 (1.29-2.59) among those who experienced discrimination. In the stratified analysis by sociodemographic and job-related factors, all the interactions did not reach statistical significance (p for interaction > 0.20). CONCLUSION: Experience of COVID-19-related discrimination was associated with severe psychological distress among HCWs. During the pandemic, effective measures should be taken to prevent the development of negative mental health outcomes in HCWs who experience discrimination.

[CD5- and CD10-positive MYC and BCL2 double-expressor diffuse large B-cell lymphoma with MYD88L265P mutation: a case report and literature review].

A 75-year-old man who had lymphadenopathy was admitted to our hospital. Histopathological examination of cervical lymph node biopsy specimens showed diffuse proliferation of lymphoma cells with large nuclei. In immunohistochemistry, the lymphoma cells were positive for CD5, CD10, CD20, BCL2, BCL6, and MYC. The patient was diagnosed with CD5- and CD10-positive diffuse large B-cell lymphoma (DLBCL). MYD88L265P mutations have been detected in DLBCL. Partial response was achieved after six courses of R-THP-COP therapy. However, the patient died because of disease progression 18 months after the diagnosis. On autopsy, lymphoma cells were found in the lymph nodes throughout the body, central nervous system, adrenals, and skin. CD5- and CD10-positive DLBCL account for 0.5-1% of DLBCL cases and have a very poor disease prognosis. This is a rare case of CD5- and CD10-positive DLBCL with MYC and BCL2 expressions harboring MYD88L265P mutation.

Group Cognitive-Behavioral Therapy With Interoceptive Exposure for Drug-Refractory Irritable Bowel Syndrome: A Randomized Controlled Trial.

INTRODUCTION: Few people can access psychotherapy for irritable bowel syndrome (IBS). Group cognitive-behavioral therapy (GCBT) may be efficient, but the evidence for its efficacy is weak and limited. We aimed to assess the efficacy and safety of GCBT with interoceptive exposure (GCBT-IE), a novel form of GCBT for drug-refractory IBS. METHODS: A single-center, open-label, randomized, controlled trial was conducted in Japan among people aged 18-75 years with moderate-to-severe drug-refractory IBS. Participants were stratified by IBS severity and allocated 1:1 to 10-week GCBT-IE or waiting list (WL) in a blockwise randomization by independent staff. Both arms practiced self-monitoring and received treatment as usual. Multiple primary outcomes were changes from baseline to week 13 in the IBS Symptom Severity Score and the IBS Quality of Life Measure (IBS-QOL), assessed in the intention-to-treat sample. RESULTS: A total of 114 people with drug-refractory IBS were randomized to GCBT-IE (n = 54) or WL (n = 60). Forty-nine participants (90.7%) in the GCBT-IE arm and 58 (96.7%) in the WL arm completed the week 13 assessment. Participants in the GCBT-IE arm reported greater improvements in both IBS symptom severity and quality of life compared with the WL arm, with -115.8 vs -29.7 on the IBS Symptom Severity Score (a difference of -86.1, 95% confidence interval -117.3 to -55.0), and 20.1 vs -0.2 on the IBS-QOL (a difference of 20.3, 95% confidence interval 15.2-25.3), respectively. Six unexpected serious adverse events were reported but were judged as unrelated to the interventions. DISCUSSION: GCBT-IE is an efficacious, safe, and efficient treatment option for people with drug-refractory IBS.

Feasibility study of adjuvant chemotherapy with S-1 after curative esophagectomy following neoadjuvant chemotherapy for esophageal cancer.

BACKGROUND: Despite advances in surgical techniques, long-term survival after esophagectomy for esophageal cancer remains unacceptably low, and more effective perioperative chemotherapy is expected. However, an important concern regarding the application of postoperative adjuvant chemotherapy is treatment toxicity. We aimed to evaluate the feasibility of adjuvant chemotherapy with S-1 in patients after esophagectomy. METHODS: We investigated the tolerability of a 2-week administration followed by 1-week rest regimen of S1 as postoperative adjuvant therapy in 20 patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy (NAC) and 22 patients who did not receive NAC during 2011-2020. RESULTS: In the non-NAC group, the mean and median relative dose intensity (RDI) were 78.7% and 99.4%, respectively, and 11 patients (50%) had altered treatment schedules. The corresponding rates in the NAC group were 77.9% and 100%, respectively, and nine patients (45%) had altered treatment schedules, with no significant difference among the groups. Moreover, 17 patients (77.2%) in the non-NAC group and 16 patients (80.0%) in the NAC group continued S-1 treatment as planned for one year postoperatively, with no significant difference in the S-1 continuation rate (p = 0.500). Seventeen of 22 patients (77.3%) and 15 of 20 patients (75.0%) experienced several adverse events in the non-NAC and NAC groups, respectively. The frequency, severity, and type of adverse events were consistent among patients with and without NAC. CONCLUSIONS: S-1 could be safely and continuously administered as adjuvant chemotherapy for patients with esophageal cancer regardless of NAC. Long-term prognosis should be evaluated for S-1 to become the standard treatment after esophagectomy.

Characteristics, Antithrombotic Patterns, and Prognostic Outcomes in Claudication and Critical Limb-Threatening Ischemia Undergoing Endovascular Therapy.

PURPOSE: The underlying difference between intermittent claudication (IC) and critical limb-threatening ischemia (CLTI) still remains unclear. This prospective multicenter observational study aimed to clarify differences in clinical features and prognostic outcomes between IC and CLTI, and prognostic factors in patients undergoing endovascular therapy (EVT). MATERIALS AND METHODS: A total of 692 patients with 808 limbs were enrolled from 20 institutions in Japan. The primary measurements were the 3-year rates of major adverse cardiovascular event (MACE) and reintervention. RESULTS: Among patients, 79.0% had IC and 21.0% had CLTI. Patients with CLTI were more frequently women and more likely to have impaired functional status, undernutrition, comorbidities, hypercoagulation, hyperinflammation, distal artery disease, short single antiplatelet and long anticoagulation therapies, and late cilostazol than patients with IC. Aortoiliac and femoropopliteal diseases were dominant in patients with IC and infrapopliteal disease was dominant in patients with CLTI. Patients with CLTI underwent less frequently aortoiliac intervention and more frequently infrapopliteal intervention than patients with IC. Longitudinal change of ankle-brachial index (ABI) exhibited different patterns between IC and CLTI (pinteraction=0.002), but ABI improved after EVT both in IC and in CLTI (p<0.001), which was sustained over time. Dorsal and plantar skin perfusion pressure in CLTI showed a similar improvement pattern (pinteraction=0.181). Distribution of Rutherford category improved both in IC and in CLTI (each p<0.001). Three-year MACE rates were 20.4% and 42.3% and 3-year reintervention rates were 22.1% and 46.8% for patients with IC and CLTI, respectively (log-rank p<0.001). Elevated D-dimer (p=0.001), age (p=0.043), impaired functional status (p=0.018), and end-stage renal disease (p=0.019) were independently associated with MACE. After considering competing risks of death and major amputation for reintervention, elevated erythrocyte sedimentation rate (p=0.003) and infrainguinal intervention (p=0.002) were independently associated with reintervention. Patients with CLTI merely showed borderline significance for MACE (adjusted hazard ratio 1.700, 95% confidence interval 0.950-3.042, p=0.074) and reintervention (adjusted hazard ratio 1.976, 95% confidence interval 0.999-3.909, p=0.05). CONCLUSIONS: The CLTI is characterized not only by more systemic comorbidities and distal disease but also by more inflammatory coagulation disorder compared with IC. Also, CLTI has approximately twice MACE and reintervention rates than IC, and the underlying inflammatory coagulation disorder per se is associated with these outcomes. CLINICAL IMPACT: The underlying difference between intermittent claudication (IC) and critical limb-threatening ischemia (CLTI) still remains unclear. This prospective multicenter observational study, JPASSION study found that CLTI was characterized not only by more systemic comorbidities and distal disease but also by more inflammatory coagulation disorder compared to IC. Also, CLTI had approximately twice major adverse cardiovascular event (MACE) and reintervention rates than IC. Intriguingly, the underlying inflammatory coagulation disorder per se was independently associated with MACE and reintervention. Further studies to clarify the role of anticoagulation and anti-inflammatory therapies will contribute to the development of post-interventional therapeutics in the context of peripheral artery disease.

Long-Term Outcomes in Elderly Patients After Deferral of Coronary Revascularization Guided by Fractional Flow Reserve.

BACKGROUND: Little evidence is available regarding the long-term outcome in elderly patients after deferral of revascularization based on fractional flow reserve (FFR).Methods and Results: From the J-CONFIRM registry (long-term outcomes of Japanese patients with deferral of coronary intervention based on fractional flow reserve in multicenter registry), 1,262 patients were divided into 2 groups according to age: elderly and younger patients (aged ≥75 or <75 years, respectively). The primary endpoint was the cumulative 5-year incidence of target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction (TVMI), and clinically driven target vessel revascularization (CDTVR). Cumulative 5-year incidence of TVF was not significantly different between elderly and younger patients (14.3% vs. 10.8%, P=0.12). Cardiac death occurred more frequently in elderly patients than younger patients (4.4% vs. 0.8%, P<0.001), whereas TVMI and CDTVR did not differ between groups (1.3% vs. 0.9%, P=0.80; 10.7% vs. 10.1%, P=0.80, respectively). FFR values in lesions with diameter stenosis <50% were significantly higher in elderly patients than in younger patients (0.88±0.07 vs. 0.85±0.07, P=0.01), whereas this relationship was not observed in those with diameter stenosis ≥50%. CONCLUSIONS: Elderly patients had no excess risk of ischemic events related to the deferred coronary lesions by FFR, although FFR values in mild coronary artery stenosis were modestly different between elderly and younger patients.

Study on Catalpol Content in Rehmannia glutinosa Root, an Important Ingredient in Kampo Prescriptions.

Rehmannia glutinosa is an important medicinal plant in Asia, and its roots are used as an ingredient in herbal medicine. However, the roots exhibit different medicinal effects depending on the processing conditions. Since the catalpol content differs greatly during the process, the catalpol content is an essential index for quality evaluation. R. glutinosa roots have various weights, diameters, and lengths, and there are differences between individuals and within an individual immediately after harvest. We found that, catalpol content in the roots tended to increase as root diameter increased. Furthermore, it has been reported that catalpol content decreased with drying, and our results also supported this phenomenon. To clarify the reason for the decrease in catalpol content, we investigated the effect of ß-glucosidase in R. glutinosa cells. An in situ assay for ß-glucosidase activity revealed that the activity in the tissue inside the cambium disappeared one month after drying under natural conditions, and the activity in the tissue outside the cambium completely disappeared after two months. Because catalpol content remained almost unchanged even after drying for two months, it was clarified that ß-glucosidase activity had minimal involvement in the decrease in catalpol content in R. glutinosa roots. Based on the above results, we proposed that slicing the roots and rapidly removing water by natural drying is best to obtain dry root with little loss of catalpol content.

Development of SCAR Markers to Identify Medicinal Cultivars of Paeonia lactiflora.

Paeoniae Radix, the dried root of Paeonia lactiflora, is one of the most important ingredients in Kampo medicine. It is known that Paeoniae Radix is derived from various P. lactiflora cultivars, including medicinal and horticultural cultivars, and that cultivar identification by DNA analysis has been unsuccessful. We attempted to develop sequence characterized amplified region (SCAR) markers as useful DNA markers for the identification and herbal medicine authentication of two cultivars developed in Japan, 'Bonten' and 'Kitasaisho,' which are two superior medicinal strains of P. lactiflora. Sequence-related amplified polymorphism (SRAP) analysis was conducted on fourteen P. lactiflora cultivars, and polymorphic fragments specific to 'Bonten' or 'Kitasaisho' were detected. Then, SCAR markers for 'Bonten' and 'Kitasaisho' were developed from the sequence information of these polymorphic fragments. Thirty cultivars of P. lactiflora and five herbal medicine samples were used to validate the specificity of the developed SCAR markers. As a result, we confirmed that our SCAR markers can identify 'Bonten' or 'Kitasaisho' from the plant samples and the herbal medicine samples. Thus, we have successfully designed two highly specific DNA markers and established an easy, rapid, and cost-efficient method to identify specific cultivars of P. lactiflora. Our SCAR markers are expected to contribute to the maintenance of P. lactiflora cultivars such as 'Bonten' as superior medicinal strains, the development of more elite cultivars in the future, and the deterrence of outflow of original cultivars to foreign countries.

Development of Highly Sensitive Method for Sugar Determination in Herbal Medicine; Application of Monosaccharides and Oligosaccharides in Japanese Angelica Root and Rehmannia Root.

We have developed a simple and accurate method for quantifying sugars in herbal medicines, which have hitherto been difficult to quantify. Using ultra performance liquid chromatography-quadrupole-time-of-flight (UPLC-Q-TOF)-MS and two types of columns with different chemical properties, we determined the optimum conditions for separating nine sugars (fructose, galactose, glucose, mannitol, sucrose, melibiose, raffinose, manninotriose, and stachyose) commonly found in herbal medicines. Separation was completed within 10 min when an apHera NH2 HPLC column was used, although galactose and glucose could not be separated. On the other hand, the nine sugars were completely separated within 16 min when a hydrophilic interaction chromatography (HILIC)pak VG-50 2D column was used. The calibration curves obtained using those two columns gave good linearity for the sugar standards, and the coefficient of determination was 0.995 or higher. Both columns showed excellent performance with short analysis time and high sensitivity. Using our developed method, we were able to quantify sugars in galactose-free herbal medicines within 10 min and in herbal medicines containing galactose within 16 min. We revealed that our method could be used for the analysis of sugars in Angelica acutiloba and Rehmannia glutinosa roots.

Efficacy and Acceptability of Remote Cognitive Behavioral Therapy for Patients With Major Depressive Disorder in Japanese Clinical Settings: A Case Series.

Remote cognitive and behavioral therapy (CBT) via videoconference has been garnering attention as a means of improving access to CBT for depression, in particular during the coronavirus disease 2019 pandemic. However, there is a lack of evidence supporting its implementation in Japanese clinical settings. This case series aimed to establish preliminary evidence of whether remote CBT can be an effective therapy for major depression in Japanese clinical settings. Five patients who met the diagnostic criteria for major depressive disorder were enrolled and underwent remote CBT via videoconference and face-to-face assessment interviews. The results showed that remote CBT via videoconference improved depressive symptoms, enabling a relatively high level of patient satisfaction and working alliance. Moreover, detailed feedback from our patients showed that continuous monitoring was preferable for increasing treatment engagement. Further research is warranted to test the efficacy and acceptability of remote CBT via videoconference for treating major depression.

A comprehensive study on the relieving effect of Lilium brownii on the intestinal flora and metabolic disorder in p-chlorphenylalanine induced insomnia rats.

CONTEXT: The bulb of Lilium brownii F. E. Brown (Liliaceae) (LB) is a common Chinese medicine to relieve insomnia. OBJECTIVE: To investigate the molecular mechanism of LB relieving insomnia. MATERIALS AND METHODS: Insomnia model was induced by intraperitoneally injection p-chlorophenylalanine (PCPA) in Wistar rats. Rats were divided into three groups: Control, PCPA (400 mg/kg, i.p. 2 days), LB (598.64 mg/kg, oral 7 days). The levels of 5-hydroxytryptamine (5-HT), norepinephrine (NE), melatonin (MT), and the expression of GABAA, 5-HT1A and MT receptors, as well as pathological changes in hypothalamus, were evaluated. 16S rDNA sequencing and UPLC-MS/MS were used to reveal the change of the intestinal flora and metabolic profile. RESULTS: The adverse changes in the abundance and diversity of intestinal flora and faecal metabolic phenotype altered by PCPA in rats were reversed after LB treatment, accompanied by the up-regulated levels of 5-HT as 8.14 ng/mL, MT as 16.16 pg/mL, 5-HT1A R and GABAA R, down-regulated level of NE as 0.47 ng/mL, and the improvement of pathological phenomena of cells in the hypothalamus. And the arachidonic acid metabolism and tryptophan metabolism pathway most significantly altered by PCPA were markedly regulated by LB. Besides, it was also found that LB reduced the levels of kynurenic acid related to psychiatric disorders and trimethylamine-N-oxide associated with cardiovascular disease. CONCLUSION: The mechanism of LB relieving insomnia involves regulating flora and metabolites to resemble the control group. As a medicinal and edible herb, LB could be considered for development as a health-care food to relieve increasing insomniacs in the future.

Ephedra Herb, Mao, Inhibits Antigen-Induced Mast Cell Degranulation by Induction of the Affinity Receptor for IgE Internalization.

PURPOSE: Ephedra herb (Mao) exerts potent anti-allergic effects. This study aimed to examine the underlying mechanisms of Mao on allergic inflammation using in vitro cultured mast cells (MCs) and an in vivo model of MC-dependent anaphylaxis. METHODS: Bone marrow-derived MCs (BMMCs) were presensitized with anti-2,4-dinitrophenol (DNP) immunoglobulin E (IgE) and challenged with antigens (Ag; DNP-human serum albumin). Degranulation responses and cell surface high-affinity receptor for IgE (FcεRI) expression were assessed with/without Mao treatment. Passive systemic anaphylaxis (PSA)-treated mice were administered Mao and the pathophysiological responses were evaluated. RESULTS: Mao inhibited Ag-induced BMMC degranulation, but not polyclonal activation with phorbol 12-myristate 13-acetate (PMA) and ionomycin, indicating that Mao inhibits IgE-dependent activation of BMMCs. Mao-treated BMMCs exhibited significant reductions in expression of surface IgE and its receptor FcεRI. Analysis of subcellular localization revealed that Mao induces FcεRI internalization in BMMCs without degranulation. In the PSA mouse model, Mao administration prevented antigen-induced hypothermia. Mao administration significantly reduced cell surface expression of IgE-bound FcεRI on peritoneal MCs. CONCLUSIONS: Mao induced FcεRI internalization in MCs, thereby inhibiting Ag-induced IgE-dependent degranulation. The inhibitory effects of Mao on MC degranulation may offer a novel therapeutic approach for allergic diseases.

Comparative Study of Tacrolimus and Short-Term Methotrexate: 2-Day versus 3-Day Methotrexate as Graft-versus-Host-Disease Prophylaxis after Umbilical Cord Blood Transplantation in Adults.

Methotrexate (MTX) in combination with a calcineurin inhibitor has been commonly used for prophylaxis of graft-versus-host disease (GVHD) following umbilical cord blood transplantation (UCBT) in Japan. However, the appropriate prophylactic MTX dosage in UCBT has not been established to date. To determine the preferential GVHD prophylaxis in UCBT, this study retrospectively investigated the administration of short-term MTX for 2 days versus 3 days. Of 103 adult patients submitted to UCBT enrolled in the study, 73 received tacrolimus (TAC) with 2 days of MTX given at 10 mg/m2 on day 1 and 7 mg/m2 on day 3 (very short-term [vs] MTX), whereas 30 patients received TAC with 3 days of MTX given at 10 mg/m2 on day 1, 7 mg/m2 on day 3, and 7 mg/m2 on day 6 (short-term [s] MTX). In univariate analysis, neutrophil engraftment was shown to be significantly better (P = .039) in the vsMTX/TAC group. Among high-risk patients, the vsMTX/TAC group also exhibited earlier neutrophil engraftment (P = .042); however, the incidence of acute GVHD was higher in the vsMTX/TAC group (P = .035) on univariate analysis. In multivariate analysis, compared with sMTX/TAC, vsMTX/TAC was associated with lower risk of relapse (hazard ratio, .27; 95% confidence interval, .11 to .64; P = .003) . These results suggest that vsMTX/TAC can be appropriate GVHD prophylaxis after UCBT, especially in higher-risk patients.

Group cognitive behavioural therapy (GCBT) versus treatment as usual (TAU) in the treatment of irritable bowel syndrome (IBS): a study protocol for a randomized controlled trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a common disease that affects the quality of life (QOL) and social functioning of sufferers. Visceral anxiety is currently considered a key factor in the onset and exacerbation of IBS, and cognitive-behavioural therapy (CBT) targeting visceral anxiety is thought to be effective. However, access to CBT is limited due to the lack of trained therapists, the substantial time required for therapy and the associated costs. Group CBT (GCBT) may solve some of these problems. We have therefore planned this trial to examine the efficacy of GCBT for IBS. METHODS: The trial is a two-armed, parallel group, open label, stratified block randomized superiority trial. The study group will consist of 112 participants (aged 18-75 years) with IBS (Rome-III or IV criteria). Participants will be randomly allocated 1:1 to (i) the intervention group: ten-week GCBT plus treatment as usual (TAU) or (ii) the control group: waiting list (WL) plus TAU. The co-primary outcomes are the change in IBS severity or disease-specific quality of life from baseline to week 13 which is 1 month after the end of treatment. The efficacy of GCBT for IBS will be examined through mixed-effects repeated-measures analysis. DISCUSSION: GCBT, if found effective, can address the issues of the shortage of therapists as well as the time required and the costs associated with individual CBT. Clinically, the findings will help make effective CBT programmes accessible to a large number of distressed IBS patients at lower costs. Theoretically, the results will clarify the relationship between IBS and psychological stress and will help elucidate the underlying mechanisms of IBS. TRIAL REGISTRATION: UMIN, CTR-UMIN000031710. Registered on March 13, 2018.

In Asian women undergoing total knee arthroplasty, lower leg morphology in those with rheumatoid arthritis differed from those with osteoarthritis.

Objectives: This retrospective, single-center study aimed to compare leg morphology between patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA) undergoing total knee arthroplasty (TKA).Methods: We enrolled 70 RA and 327 OA female patients undergoing TKA. Hip-knee-ankle angle (HKA), femorotibial angle (FTA), valgus correction angle (VCA), and femoral/tibial bowing were measured using full-length radiographs. Femoral bowing of more than 3° or tibial bowing more than 2°, either laterally or medially, was considered substantial. Distribution of these results and the incidence of substantial bowing in RA and OA were compared.Results: HKA, FTA, and VCA were significantly smaller in RA than those in OA. Femoral bowing was significantly smaller in RA (mean angle: 0.04° ± 3.1°) than that in OA (mean angle: 2.1° ± 3.6°) (p < .05). In almost half of the patients with RA (48.6%), femoral bowing occurred medially, whereas femoral bowing occurred laterally in approximately three quarters of OA patients (73.1%). Tibial bowing did not differ. The incidence of substantial femoral bowing was significantly lower in RA (27.1%) than that in OA (43.0%) (p < .05).Conclusion: RA patients undergoing TKA had different leg morphology than OA patients. These findings have implications for surgical planning.

Monitoring TIGIT/DNAM-1 and PVR/PVRL2 Immune Checkpoint Expression Levels in Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia.

After allogeneic stem cell transplantation (alloSCT), several immune checkpoints play an important role in the antileukemic immune response in the bone marrow (BM) microenvironment. However, immune checkpoint expression levels in the BM have not been reported after alloSCT in patients with acute myeloid leukemia (AML). We investigated the clinical impact of immune checkpoint expression in BM samples after alloSCT for AML. Higher expression of T cell immunoreceptor with Ig and ITIM domains (TIGIT) was associated with a decreased incidence of acute graft-versus-host disease (P = .048) and poor overall (P = .046) and progression-free survival (P = 0.024). In addition, higher expression of TIGIT at engraftment after alloSCT was correlated with a decreased number of natural killer cells in BM (P = .019). Monitoring TIGIT expression in the BM could be useful for predicting outcome after alloSCT for AML. Our findings raise the possibility that blockade of TIGIT would improve survival.

[Development of cardiac tamponade and emergence of arrhythmia during chemotherapy for diffuse large B-cell lymphoma].

Cardiac involvement during lymphoma often causes complications, including arrhythmia. A 68-year-old male with cardiac tamponade was diagnosed with diffuse large B-cell lymphoma with cardiac involvement based on the presence of the tumor mass in the myocardium and lymphoma cells in the pericardial effusion. He developed atrial fibrillation, ventricular tachycardia, and atrial flutter after initiating chemotherapy. Following chemotherapy, sinus rhythm was restored without invasive treatment for arrhythmia, while the cardiac mass disappeared. No recurrent arrhythmias were observed. In lymphoma with cardiac involvement, unexpected arrhythmias can emerge after initiation of chemotherapy, which could potentially be related to accelerated cardiac remodeling owing to the rapid relief of cardiac damage. Follow-up using electrocardiogram is thus necessary during chemotherapy for cardiac lymphoma, despite the absence of arrhythmia at the time of diagnosis.

Status of Natural Killer Cell Recovery in Day 21 Bone Marrow after Allogeneic Hematopoietic Stem Cell Transplantation Predicts Clinical Outcome.

Rapid immune recovery following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is important for clinical outcome prediction. In most studies, immune recovery after allo-HSCT is monitored via peripheral blood. However, few reports regarding the status of absolute lymphocyte subsets in the bone marrow (BM) microenvironment have been undertaken. Therefore, we evaluated the clinical impact of immune recovery in the early period following allo-HSCT using BM samples. We showed that delayed natural killer cell recovery was independently associated with a poor prognosis for overall survival (hazard ratio [HR], 3.07; 95% confidence interval [CI], 1.37- 6.89; P = .007), progression-free survival (HR, 3.42; 95% CI, 1.47-7.94; P = .004), and nonrelapse mortality (HR, 6.68; 95% CI, 1.82-25.0; P = .004) by multivariate analysis. In addition, low NK cell counts were associated with the presence of 1 or more bacterial, viral, or fungal infections. Our results indicate that investigating absolute lymphocyte subsets in BM in the early phase following allo-HSCT can be useful for predicting and improving survival outcomes.