Dupilumab Leads to Clinical Improvements including the Acquisition of Tolerance to Causative Foods in Non-Eosinophilic Esophagitis Eosinophilic Gastrointestinal Disorders.

A recent report showed that most pediatric cases of non-eosinophilic esophagitis (EoE) eosinophilic gastrointestinal disorders (EGIDs) (non-EoE EGIDs) are persistent and severe compared with those of EoE, thus requiring further effective therapeutic approaches. In this study, we present the first case based on a systematic search of non-EoE EGID for which tolerance to causative foods and histological and symptomatic improvements were achieved following dupilumab administration, after elimination diets and omalizumab and mepolizumab treatments. Driven by this case, we investigated the efficacies of biological treatments in non-EoE EGID cases based on the patient studied herein, and other patients identified in the conducted systematic review. Seven articles, including five different biologics, were reviewed. Both clinical efficacies and impact differences among the targeted molecules are demonstrated in this study. Our findings show that dupilumab may affect mechanisms that can suppress symptoms induced by offending foods that are different from those induced by other biologics as identified in the conducted systematic review. Additional studies are required to address the unmet needs of non-EoE EGID treatments.

Challenges of Agitation in Dementia: A Plea for Early Discussion.

ABSTRACT: Behavioral and psychological symptoms of dementia (BPSD) occur frequently among people with dementia and are known precipitants for placement in care facilities. Despite the social, financial, and psychological impact on dementia care, education and discussions on BPSD have not been routinely included in advance care planning (ACP). As a result, families can face great challenges in making complex medical decisions when their loved ones are admitted to the geriatric psychiatric inpatient unit with refractory BPSD. We present the case of an 83-year-old gentleman with BPSD to illustrate universal struggles in dementia care experienced by many families, which could have been alleviated by education and discussions around BPSD earlier in the patient's dementia course. A literature search did not yield any articles that mention discussions of BPSD in ACP. The lack of literature referencing BPSD in ACP supports our clinical experiences with the case and highlights the need for improvement in current dementia care. We propose a guideline for providers to facilitate conversations around BPSD as an integral part of ACP, including discussions of four key points related to the progressive nature of dementia, the commonality of BPSD, the lack of FDA-approved treatment for BPSD, and the difficulty in balancing agitation and sedation to allow safe placement. We firmly believe it is important to start discussion on BPSD as part of ACP as early as possible. Early education and discussion will help to facilitate meaningful care decisions as patients and families navigate the challenges associated with this progressive disease.

A young child with pediatric multisystem inflammatory syndrome successfully treated with high-dose immunoglobulin therapy.

Pediatric multisystem inflammatory syndrome (MIS-C) is a disease that presents mainly in older children after coronavirus disease 2019 (COVID-19) and is associated with Kawasaki-like symptoms and multiple-organ failure. The number of cases of MIS-C has increased since April 2020, with reports mainly from Europe and the United States. The reason is unclear, but few cases of MIS-C have been reported in Asian countries, including Japan. No treatment has been established for MIS-C. In this study, we report the case of a young boy treated with IVIg for MIS-C by measuring the cytokine profile over time. A 4-year-old boy presented with Kawasaki disease-like symptoms 28 days after a positive result from polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), meeting the World Health Organization criteria for MIS-C diagnosis. Blood tests showed lower levels of C-reactive protein and ferritin, and no decrease in lymphocyte count (<1000/µL) or more increase in fibrinogen than those reported in Japan for MIS-C in school-aged children and older. Neopterin, interleukin (IL)-6, IL-18, soluble tumor necrosis factor receptor (sTNF-R)I and sTNF-RII were all high at disease onset, but neopterin, IL-6, and sTNF-RII rapidly decreased with fever resolution after the second dose of IVIg, while IL-18 and sTNF-RI decreased bimodally. As far as we can determine, this case represents the youngest identified in Japan. The key point of difference between MIS-C and Kawasaki disease is older age in MIS-C, but attention is also needed in infants.

A Support System for Adolescent and Young Adult Patients with Cancer at a Comprehensive Cancer Center.

Cancer patients in adolescents and young adults (AYA) generation aged 15-39 years have various psychosocial needs during their treatment course such as school enrollment, finding employment, marriage, and fertility. It is difficult for medical professionals to gain experience related to providing medical care and consultation support to these kinds of AYA generation cancer patients. There is a need to provide information and establish both support and medical care systems that are able to meet the diverse needs unique to this generation. This review will explain how to launch an AYA support team (AST). We have worked and established the AST since 2016, which is medical care teams that provide support according to the life stage of each individual patient and build a multidisciplinary AYA generation patient support system. The team-building process consisted of two main projects: building and enlarging multidisciplinary team and establishing screening process of psychosocial needs of AYA generation patients. Multidisciplinary healthcare professionals got involved in the AST with already-existing patient support functions in our center: the patient support center, which is an outpatient department and the palliative care team, which is an inpatient interdepartmental team. The AST systematically finds patients in need of assistance and offers them support as a multidisciplinary team. The AST also established a procedure that systematically gathers information about the needs of patients by using a screening tool. In addition, the AST provides the following specialized services: reproductive medicine, supporting cancer patients with children, employment support, and peer support. The AST has been established and sophisticatedly worked. It can flexibly provide various psychosocial support services. This review will explain how to launch an AST.

HLA-haploidentical peripheral blood stem cell transplantation following reduced-intensity conditioning with very low-dose antithymocyte globulin for relapsed/refractory acute leukemia in pediatric patients: a single-institution retrospective analysis.

The prognosis of relapsed/refractory (R/R) pediatric acute leukemia is extremely poor. We retrospectively reviewed 20 consecutive pediatric patients with R/R acute leukemia who underwent a first HLA-haploidentical peripheral blood stem cell transplantation following reduced-intensity conditioning (haplo-RIC-PBSCT) with very low-dose antithymocyte globulin (ATG) between 2012 and 2019. Of these 20 patients, 7 patients had acute lymphoblastic leukemia, and 13 had acute myeloid leukemia. At the time of haplo-RIC-PBSCT, 15 patients had active disease. The median follow-up duration for survivors was 56 months (range 22-108 months). Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, short-term methotrexate, methylprednisolone, and ATG 1.25 mg/kg on day-2. The 2-year cumulative incidence of transplant-related mortality and relapse were 5.0% [95% confidence interval (CI) 0.7-30.5%)] and 57.8% (95% CI 37.4-79.6%), respectively. Among the 20 patients, 16 (80.0%) developed grade III-IV acute GVHD, and 2 developed severe chronic GVHD. The 2-year event-free survival and overall survival rates were 40.0% (95% CI 19.3-60.0%) and 50.0% (95% CI 27.1-69.2%), respectively. Although the sample size is small, the survival outcomes of the present study are encouraging.

Can probability neglect bias promote social distancing during the COVID-19 pandemic?

The effectiveness of a stay-at-home order depends on the speed of behavioral changes that are triggered by risk perception. Probability neglect bias, one of the cognitive biases, may lead people to engage in social distancing. However, there is no empirical evidence of the relationship between probability neglect bias and social distancing. This study aims to examine the relationship between individual differences in susceptibility to probability neglect bias and the level of social distancing practice during the early stages of the COVID-19 outbreak in Japan. The level of engagement in social distancing was defined as the narrowing of life-space mobility. We conducted a web-based questionnaire survey among 1000 adults living in central Tokyo, Japan, at the beginning of the pandemic outbreak. Our results show that people had a strong fear of infection in the early pandemic stages. Approximately 60% of our subjects were influenced by probability neglect bias. People susceptible to probability neglect bias engaged in social distancing more intensely than those who were not susceptible after the state of emergency was lifted.

Radiation-sparing reduced-intensity unrelated umbilical cord blood transplantation for rare hematological disorders in children.

Graft failure is a major pitfall of unrelated umbilical cord blood transplantation (CBT) in children with rare hematological disorders other than acute leukemia, such as acquired and inherited bone marrow failure, myelodysplastic syndrome, juvenile myelomonocytic leukemia, and chronic myeloid leukemia. We developed a less-toxic conditioning regimen for CBT that achieves a higher rate of complete donor chimerism, and retrospectively compared it against two other conditioning regimens for CBT performed at our single institution. The engraftment rate with complete donor chimerism was 100% and 5-year event-free survival (5y-EFS) was 90.9% in patients using our latest regimen (n = 11) of reduced-intensity conditioning (RIC) containing fludarabine (Flu) 180 mg/m2, melphalan (MEL) 210 mg/m2, and low-dose rabbit anti-thymocyte globulin (LD-rATG) 2.5 mg/kg without irradiation (regimen C). Outcomes were better than in patients (n = 10) treated with previous regimens involving irradiation (5y-EFS 30.0%, p = 0.004): regimen A, consisting of myeloablative conditioning containing cyclophosphamide (CY) and total body irradiation (TBI) with 8-12 Gy, or regimen B, consisting of RIC with Flu, CY, horse ATG, and thoracoabdominal irradiation (TAI) with 6 Gy. In conclusion, Flu/MEL/LD-rATG (regimen C) without TBI/TAI may be preferable as RIC for unrelated CBT in children with rare hematological disorders.

[Investigation the contents of employment consultation and support in a cancer center hospital].

OBJECTIVES: This study aimed to analyze and categorize the actual situation of employment consultation and support according to consultation times or employment status at the Consultation Support Center of the National Cancer Center Hospital of Japan. METHODS: We retrospectively analyzed the patient backgrounds, consultation contents, and the number of employment consultation cases conducted at the Consultation Support Center of the National Cancer Center Hospital during a 6-month period from May to December 2018. RESULTS: During the study period, 117 patients (male: female = 46:71) visited the Consultation Support Center. The median age of patients was 48 years old. The most common primary cancer site was the breast in 28 patients followed by the lung in 16 patients, and then gynecologic cancer in 10 patients. The most common cancer treatment was chemotherapy in 53 patients (45.3%), and 12 patients (10.2%) were recurrent patients. Fifty-two patients were in regular employment, 24 were unemployed, 17 were of unknown employment status, 16 were in non-regular employment, and 8 were classified/categorized as other. In terms of working status, 40 were on leave, 35 were working, 15 were seeking work, 8 were unemployed, and 19 were categorized as other. The median number of consultations was 1 (1,11). The content of consultations was the social security system in 44 cases (37.6%) job seeking in 24 cases (20.5%), how to inform the workplace in 14 cases (12%), and workplace environment adjustment in 13 cases (11.1%). CONCLUSIONS: We conducted a survey on the actual status of employment consultation in a cancer center hospital. The majority of consultations were completed in one session. In terms of the content of consultations, there was a high need for consultations on the social security system and job seeking. Further study is needed on the characteristics of employment consultations according to employment status and other attributes.

Sudden unexpected death caused by infantile acute lymphoblastic leukaemia.

A 7-week-old girl with a normal birth history suddenly developed respiratory distress while feeding. Cardiopulmonary resuscitation was initiated at home after she had a cardiac arrest and was continued in the emergency room but all efforts at resuscitation proved unsuccessful and she died 2 h after presentation. Investigations performed in the emergency room revealed that she had a significantly high white blood cell count and severe anaemia. The cause of death was identified as KMT2A-rearranged infantile acute lymphoblastic leukaemia based on cytogenetic tests. She had no abnormalities at the 4-week check-up; however, she developed a skin nodule on her abdomen thereafter, and the family did not consult a doctor for fear of contracting COVID-19. Early detection and diagnosis could have changed the prognosis of the patient. The present case highlights the negative impact of the reduction of outpatient consultations during the COVID-19 pandemic.

Psychological Reactance to Mobility Restrictions Due to the COVID-19 Pandemic: A Japanese Population Study.

In Japan, mobility restrictions were enforced by the government to abate the spread of COVID-19. The current study examined whether experiences of such mobility restrictions affected motivation for future going-out activities. To this end, we conducted a one-time online survey of 1,000 adults in Tokyo to measure going-out activities in four different time periods at once: before the spread of infection, during and after the emergency declaration, and after the end of the pandemic (future desire). In addition, to examine the impact of preferences for online services that make it easier to stay home, we measured the usage history of online services to obtain food during the mobility restriction period. Results indicated that desire for going-out activities after the end of the pandemic increased compared with those before the pandemic, particularly for leisure-related purposes. In addition, the use of online services to obtain food tended to suppress the increased desire for future going-out activities, although this effect was not significant. In conclusion, mobility restrictions resulted in motivational arousal for going-out activities after the end of the pandemic. Our findings indicate that psychological reactance plays a role in determining going-out activities in the future.

A Bornean peat swamp forest is a net source of carbon dioxide to the atmosphere.

Tropical peat forests are a globally important reservoir of carbon, but little is known about CO2 exchange on an annual basis. We measured CO2 exchange between the atmosphere and tropical peat swamp forest in Sarawak, Malaysia using the eddy covariance technique over 4 years from 2011 to 2014. The CO2 fluxes varied between seasons and years. A small carbon uptake took place during the rainy season at the beginning of 2011, while a substantial net efflux of >600 g C/m2 occurred over a 2 month period in the middle of the dry season. Conversely, the peat ecosystem was a source of carbon during both the dry and rainy seasons in subsequent years and more carbon was lost during the rainy season relative to the dry season. Our results demonstrate that the forest was a net source of CO2 to the atmosphere during every year of measurement with annual efflux ranging from 183 to 632 g C m-2  year-1 , noting that annual flux values were sensitive to gap filling methodology. This is in contrast to the typical view of tropical peat forests which must have acted as net C sinks over time scales of centuries to millennia to create the peat deposits. Path analyses revealed that the gross primary productivity (GPP) and ecosystem respiration (RE) were primarily affected by vapour pressure deficit (VPD). Results suggest that future increases in VPD could further reduce the C sink strength and result in additional net CO2 losses from this tropical peat swamp forest in the absence of plant acclimation to such changes in atmospheric dryness.

Impact of melphalan dose during reduced-intensity conditioning on engraftment of cord blood transplantation for chronic Epstein-Barr virus-associated T or NK cell lymphoproliferative diseases.

The rejection rate in cord blood transplants for chronic Epstein-Bar virus-associated T or natural killer cell lymphoproliferative diseases using our standard reduced-intensity conditioning "LPAM140 regimen," which includes fludarabine, melphalan (LPAM), etoposide, and antithymocyte globulin, has been high. To ensure better engraftment, we increased the LPAM dose to 210 mg/m2 ("LPAM210 regimen"). Patient data (n = 22; LPAM140, n = 7; LPAM210, n = 15) were analyzed retrospectively. The engraftment rate after the LPAM210 regimen (100.0%) was significantly higher than that after the LPAM140 regimen (57.1%; P = .002). Fludarabine combined with melphalan (210 mg/m2 ) had a favorable impact on engraftment.

A Case of Childhood Blastic Phase Chronic Myeloid Leukemia With Minor BCR-ABL.

Chronic myeloid leukemia (CML) is commonly associated with major BCR-ABL transcript. We present a child with blastic phase CML associated with minor BCR-ABL transcript without prior CML diagnosis. Diagnosis was achieved by fluorescence in situ hybridization of peripheral blood neutrophils, which identified 90% as BCR-ABL positive. The patient received chemotherapy with imatinib followed by dasatinib and underwent reduced-intensity hematopoietic allogeneic stem cell transplantation with prophylactic posttransplant dasatinib for 2 years and has remained in complete molecular remission. Our intensified treatment regimen was effective compared with previous studies on minor BCR-ABL CML describing inferior outcomes with tyrosine kinase inhibitor therapy.

The exchange of water and energy between a tropical peat forest and the atmosphere: Seasonal trends and comparison against other tropical rainforests.

Tropical rainforests control the exchange of water and energy between the land surface and the atmosphere near the equator and thus play an important role in the global climate system. Measurements of latent (LE) and sensible heat exchange (H) have not been synthesized across global tropical rainforests to date, which can help place observations from individual tropical forests in a global context. We measured LE and H for four years in a tropical peat forest ecosystem in Sarawak, Malaysian Borneo using eddy covariance, and hypothesize that the study ecosystem will exhibit less seasonal variability in turbulent fluxes than other tropical ecosystems as soil water is not expected to be limiting in a tropical forested wetland. LE and H show little variability across seasons in the study ecosystem, with LE values on the order of 11 MJ m-2 day and H on the order of 3 MJ m-2 day-1. Annual evapotranspiration (ET) did not differ among years and averaged 1579 ±â€¯47 mm year-1. LE exceeded characteristic values from other tropical rainforest ecosystems in the FLUXNET2015 database with the exception of GF-Guy near coastal French Guyana, which averaged 8-11 MJ m-2 day-1. The Bowen ratio (Bo) in tropical rainforests in the FLUXNET2015 database either exhibited little seasonal trend, one seasonal peak, or two peaks. Volumetric water content (VWC) and VPD explained a trivial amount of the variability of LE and Bo in some of the tropical rainforests including the study ecosystem, but were strong controls in others, suggesting differences in stomatal regulation and/or the partitioning between evaporation and transpiration. Results demonstrate important differences in the seasonal patterns in water and energy exchange across different tropical rainforest ecosystems that need to be understood to quantify how ongoing changes in tropical rainforest extent will impact the global climate system.

High rates of ovarian function preservation after hematopoietic cell transplantation with melphalan-based reduced intensity conditioning for pediatric acute leukemia: an analysis from the Japan Association of Childhood Leukemia Study (JACLS).

Women are at high risk of hypergonadotropic hypogonadism after hematopoietic cell transplantation (HCT). Hypogonadism is universal after irradiation or busulfan. We hypothesized that reduced intensity conditioning (RIC) might protect ovarian function after HCT. We retrospectively reviewed data from patients with acute leukemia treated according to the Japan Association of Childhood Leukemia Study and nationwide multicenter study protocol. We selected 11 female patients with acute leukemia who received first HCT with RIC, had survived for three or more years after HCT, and were aged ≥ 12 years at the last follow-up visit. Median age at diagnosis, HCT, and last visit were 8, 10, and 17 years. Six patients received HLA-matched bone marrow (BM), two HLA-mismatched BM, and three cord blood. Melphalan was used as conditioning regimen in all patients. At the last visit, six of seven post-pubertal patients at transplantation recovered menstruation, and four of four patients who underwent transplantation at the pre-pubertal began menstruation. Height z scores showed no significant reduction between pre-transplant and post-transplant. No patients received growth hormone treatment. Only one recipient displayed subclinical hypothyroidism. Melphalan-based RIC may be an encouraging option for patients with acute leukemia to avoid ovarian and endocrine dysfunction after HCT.

A Content Analysis of Multidimensional Support Needs Regarding Fertility Among Cancer Patients: How Can Nonphysician Health Care Providers Support?

PURPOSE: This study aimed to identify support needs among young cancer patients regarding fertility-related issues to describe multidimensional support provided by nonphysician health care providers. METHODS: Participants were cancer patients and their families who contacted the Hotline for Cancer Treatment and Reproduction at National Cancer Center Hospital in Japan. Medical charts were analyzed through content analysis. RESULTS: A total of 51 participants met the inclusion criteria, of which 32 cases (63%) involved patients themselves, 13 (25%) patients' family members, and 6 (12%) both patients and their families. About patients' demographic status, 40% of the patients were female and 28% were in their thirties. Gynecological and breast cancer patients were the majority, and 24 patients (47%) had not yet started cancer treatment. As a result of content analysis regarding support needs, 9 categories and 55 codes were extracted. The categories included information about risk of infertility, information about means to maintain reproductive function, referral to specialists, support for economic burden, support for worry about cancer progression, support for psychological distress upon facing the risk of infertility, support for communication with oncologists, support for family relationships, and decisional aid. CONCLUSIONS: This study suggests that nonphysician health care providers should acquire knowledge about fertility preservation and provide psychological support within their specialties.