Search

We describe successful treatment of 3 cases of human herpesvirus 6 ( HHV-6) encephalitis/myelitis following cord blood transplantation ( CBT). Ganciclovir ( GCV) (10 mg/kg/day) reduced HHV-6 load to undetectable levels in cerebrospinal fluid ( CSF). Early dose reduction in the presence of HHV-6 detectable in CSF resulted in an increased HHV-6 load. GCV was capably shifted to valganciclovir ( VGCV) with an almost equivalent concentration. GCV/ VGCV may be effective for HHV-6 encephalitis/myelitis after CBT, although HHV-6 load in CSF should be monitored. [ABSTRACT FROM AUTHOR]

Chronic active Epstein-Barr virus (EBV) disease (CAEBV) is a systemic EBV-positive lymphoproliferative disorder characterized by fever, lymphadenopathy, and splenomegaly. Patients with CAEBV may present with cutaneous symptoms, including hypersensitivity to mosquito bites and hydroa vacciniforme (HV)-like eruptions. HV is a rare photodermatosis characterized by vesicles and crust formation after exposure to sunlight, with onset in childhood, and is associated with latent EBV infection. While γδ T cells have recently been demonstrated to be the major EBV-infected cell population in HV, the immunophenotypic features of EBV-infected γδ T cells in CAEBV with HV-like eruptions or HV remain largely undetermined. We describe three patients with CAEBV whose γδ T cells were found to be the major cellular target of EBV. HV-like eruptions were observed in two of these patients. A clonally expanded subpopulation of γδ T cells that were highly activated and T cell receptor Vγ9- and Vδ2-positive cells was demonstrated in all patients. We also show that the clonally expanded γδ T cells infiltrated into the HV-like eruptions in one patient from whom skin biopsy specimens were available. These results suggest the pathogenic roles of clonally expanded γδ T cells infected by EBV in patients with CAEBV and HV-like eruptions. [ABSTRACT FROM AUTHOR]

Abstract Systemic juvenile idiopathic arthritis (sJIA) is a systemic inflammatory disease characterized by arthritis, spiking fever and a skin rash that is frequently complicated by macrophage activation syndrome (MAS), a life-threatening disorder. We report a 22-month-old girl with sJIA who developed severe MAS but was successfully treated with corticosteroids, cyclosporin A, and non-steroidal anti-inflammatory drugs by monitoring serum IL-18 levels. IL-18 is an extremely useful cytokine for monitoring the activity of sJIA and MAS, and serum IL-18 can be used as an indicator for the effectiveness of treatment and the decision to discontinue therapy.

Background: Severe combined immunodeficiency (SCID) is a heterogenous disorder with profound deficiency of T/B-cell functions. The best SCID therapy requires hematopoietic stem cell transplantation (HSCT) early in life. HSCT with conditioning is necessary to achieve a long-term reconstitution of B-cell functions. However, conditioning may aggravate pre-existing infection and cause transplant-related toxicity, especially in very young infants. Hence, the intensity of conditioning should be reduced to allow the reconstitution of immunity including B cells to the extent that prevents transplant-related toxicity and delayed complications., Methods: An infant with a family history of X-linked SCID (X-SCID) was diagnosed with X-SCID disorder soon after birth. The infant exhibited cytomegalovirus (CMV) infection despite being strictly isolated. At 1.5 months of age, we performed an unrelated cord blood transplantation (CBT) with a less intensity conditioning regimen: fludarabine (125 mg/m 2 ) + melphalan (80 mg/m 2 ). We evaluated the efficacy of reconstitution by assessing B-cell function and growth and psychomotor development at 5 years and 7 months after CBT., Results: The clinical course after CBT was uneventful after CBT. The CMV infection was fully controlled by ganciclovir or foscavir therapy, which was discontinued at day 55 after CBT. Furthermore, immunoglobulin (Ig) replacement therapy was also discontinued at 6 months after CBT. A sufficient proportion of CD27 + memory B cells was developed, which was essential for an effective vaccination and prevention of infections. While the B-cell chimerism became recipient-dominant, the Ig replacement therapy was substituted by very successful post-vaccine immunity acquisition after CBT. The analysis of the general developmental parameters showed that chemotherapy did not cause any delay in growth and psychomotor development., Conclusions: The CBT therapy with this conditioning regimen was well tolerated and induced an effective reconstitution of B-cell functions in an X-SCID infant under the 3 months of age., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Proton magnetic resonance spectroscopy ( 1 H-MRS) has shown inconsistent alterations in the brain metabolites of individuals with chronic pain. We used 3T 1 H-MRS to investigate the brain metabolites in the anterior cingulate cortex and thalamus of 22 patients with chronic mild pain and no gait disturbance and 22 healthy controls. The chronic-pain group included patients with chronic low back pain and/or osteoarthritis but none suffering from hypersensitivity. There were no significant between group-differences in glutamate, glutamate plus glutamine (Glx), N-acetylaspartate, glycerophosphorylcholine (GPC), glutamine, creatine plus phosphocreatine, or myo-inositol in the anterior cingulate cortex, but the patients showed a significant decrease in GPC, but not other metabolites, in the thalamus compared to the controls. The GPC values in the patients' thalamus were significantly correlated with pain components on the Short-Form McGill Pain Questionnaire (SF-MPQ-2) and affective empathy components on the Questionnaire of Cognitive and Affective Empathy (QCAE). The GPC in the patients' anterior cingulate cortex showed significant correlations with cognitive empathy components on the QCAE. Myo-inositol in the controls' anterior cingulate cortex and Glx in the patients' thalamus each showed significant relationships with peripheral responsivity on the QCAE. These significances were not significant after Bonferroni corrections. These preliminary findings indicate important roles of GPC, myo-inositol, and Glx in the brain of patients with chronic mild pain., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Introduction: Tight filum terminale is a neurological condition marked by various symptoms, including muscle weakness. There is a notable lack of literature addressing muscle weakness, particularly in cases emerging during adolescence and beyond. The diagnosis is challenging due to a lack of radiological abnormalities, and the literature on its treatment, especially untethering, in adults is limited. This study aims to evaluate the effectiveness of untethering in improving muscle weakness and other symptoms in postadolescent patients diagnosed with tight filum terminale., Methods: A retrospective analysis was conducted on seven postadolescent patients diagnosed with tight filum terminale and presenting muscle weakness who underwent untethering at our institution between January 2018 and August 2022. Patients were monitored for muscle strength improvement, lumbar and lower extremity pain, and bowel and bladder dysfunction (BBD) after untethering., Results: Muscle weakness improved in all cases after untethering, with a mean duration of 9.1 weeks for the improvement. Patients unable to walk independently regained mobility in an average of 22.3 weeks. Lumbar and lower limb pain improved in all cases within an average of 8.1 weeks, while BBD improved in six of the seven cases within an average of 1.9 weeks., Conclusions: Our findings suggest that untethering is an effective surgical intervention for postadolescent patients diagnosed with tight filum terminale and presenting muscle weakness., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of Asahi General Hospital issued approval 2023071812. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kitamura et al.)

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by molecular defects in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. p67 phox -CGD is an autosomal recessive CGD, which is caused by a defect in the cytosolic components of NADPH oxidase, p67 phox , encoded by NCF2. We previously established a flow cytometric analysis for p67 phox expression, which allows accurate assessment of residual protein expression in p67 phox -CGD. We evaluated the correlation between oxidase function and p67 phox expression, and assessed the relevancy to genotypes and clinical phenotypes in 11 patients with p67 phox -CGD. Reactive oxygen species (ROS) production by granulocytes was evaluated using dihydrorhodamine-1,2,3 (DHR) assays. p67 phox expression was evaluated in the monocyte population. DHR activity and p67 phox expression were significantly correlated (r = 0.718, p < 0.0162). Additionally, DHR activity and p67 phox expression were significantly higher in patients carrying one missense variant in combination with one nonsense or frameshift variant in the NCF2 gene than in patients with only null variants. The available clinical parameters of our patients (i.e., age at disease onset, number of infectious episodes, and each infection complication) were not linked with DHR activity or p67 phox expression levels. In summary, our flow cytometric analysis revealed a significant correlation between residual ROS production and p67 phox expression. More deleterious NCF2 genotypes were associated with lower levels of DHR activity and p67 phox expression. DHR assays and protein expression analysis by using flow cytometry may be relevant strategies for predicting the genotypes of p67 phox -CGD., (© 2024 The Scandinavian Foundation for Immunology.)

Objective: We assess the clinical characteristics of patients with cryopyrin-associated periodic syndrome (CAPS) in Japan and evaluate the real-world efficacy and safety of interleukin-1 (IL-1) inhibitors, primarily canakinumab., Methods: Clinical information was collected retrospectively, and serum concentrations of canakinumab and cytokines were analyzed., Results: A total of 101 patients were included, with 86 and 15 carrying heterozygous germline and somatic mosaic mutations, respectively. We identified 39 mutation types, and the common CAPS-associated symptoms corresponded with those in previous reports. Six patients (5.9% of all patients) died, with four of the deaths caused by CAPS-associated symptoms. Notably, 73.7% of patients (100%, 79.6%, and 44.4% of familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurological cutaneous articular syndrome/neonatal onset multisystem inflammatory disease, respectively) achieved complete remission with canakinumab, and early therapeutic intervention was associated with better auditory outcomes. In some patients, canakinumab treatment stabilized the progression of epiphysial overgrowth and improved height gain, visual acuity, and renal function. However, 23.7% of patients did not achieve inflammatory remission with crucial deterioration of organ damage, with two dying while receiving high-dose canakinumab treatment. Serological analysis of canakinumab and cytokine concentrations revealed that the poor response was not related to canakinumab shortage. Four inflammatory nonremitters developed inflammatory bowel disease (IBD)-unclassified during canakinumab treatment. Dual biologic therapy with canakinumab and anti-tumor necrosis factor-α agents was effective for IBD- and CAPS-associated symptoms not resolved by canakinumab monotherapy., Conclusion: This study provides one of the largest epidemiologic data sets for CAPS. Although early initiation of anti-IL-1 treatment with canakinumab is beneficial for improving disease prognosis, some patients do not achieve remission despite a high serum concentration of canakinumab. Moreover, IBD may develop in CAPS after canakinumab treatment., (© 2024 American College of Rheumatology.)

This article describes three cases in which a dislocated hip prosthesis was reduced by a new reduction technique - that we previously described - using traction table. The dissociation of a prosthesis is a rare but serious complication of closed reduction manoeuvre. The new reduction manoeuvre using a traction table may be a good option to avoid dissociation of the prosthesis during closed reduction for treatment of dislocation after total hip arthroplasty., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Dislocation is a major complication of total hip arthroplasty (THA). The modular femoral neck system provides practical advantages by allowing adjustment of neck version and length in the presence of intraoperative instability. Anatomical studies have identified morphological differences in the hip joint between men and women. Despite sex-based differences in hip morphology, it remains unclear whether such differences affect neck selectivity in THA using a modular neck system and whether this approach achieves anatomical reconstruction, thereby reducing complications such as dislocation. This study aimed to investigate gender differences in neck selectivity in THA with the modular neck system and assess the clinical impact of the modular neck system., Methods: A total of 163 THAs using a modular neck system were included in this study. Data on the type of modular neck and intraoperative range of motion (ROM) were retrieved from patient records. Pre- and post-operative leg length differences (LLD) were examined as part of the radiographic assessment. Dislocation was investigated as a postoperative complication., Results: Neck selectivity did not significantly differ between men and women. The comparison of pre- and post-operative LLD revealed a tendency for varus necks to improve LLD more than version-controlled necks. Furthermore, no significant correlation was found between intraoperative ROM and neck selectivity, or postoperative dislocation and neck selectivity., Conclusions: This study on THA with a modular neck system provided valuable insights into sex-based differences in neck selectivity and highlighted the potential benefits of the modular neck system in addressing LLD and preventing postoperative dislocation., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The pararectus (PR) approach combines the advantages of the second window of the ilioinguinal approach and the medial view of the modified Stoppa approach. However, it is unclear whether the PR approach is more effective or safer than the other approaches, as few clinical studies have compared the PR approach with the other approaches. The aim of this study was to provide a systematic review and meta-analysis comparing the PR approach with the other approaches for the treatment of acetabular fractures and to answer the following question: Are the results of the PR approach superior to those of the other approaches in terms of reduction quality, operative time, operative blood loss, complications, and clinical outcomes for treatment of acetabular fractures?, Patients and Methods: A systematic literature review was conducted using relevant original studies from various databases. Pooling of data was performed using RevMan software (version 5.3, Cochrane Collaboration, Oxford, UK). A p-value<0.05 was considered to be significant. We calculated the mean differences for continuous data and odds ratio for dichotomous data with 95% confidence intervals for each outcome. Statistical heterogeneity was assessed based on I 2 using the standard χ 2 test., Results: Five studies were included in this meta-analysis. The findings demonstrated that operative blood loss was significantly lower in the PR approach than in the other approaches (p=0.04). There was no significant difference in the rate of anatomical reduction, the operative time, the rate of complications, and the rate of excellent or good clinical score between the PR approach and the other approaches., Discussion: The PR approach provided lower operative blood loss, although there was no significant difference in reduction quality, operative time, complications, and excellent or good clinical score between the PR approach and the other approaches., Level of Evidence: III., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: The immune checkpoint HERV-H LTR-associating 2 (HHLA2) is expressed in kidney cancer and various other tumor types. Therapeutics targeting HHLA2 or its inhibitory receptor KIR3DL3 are being developed for solid tumors, including renal cell carcinoma (RCC). However, the regulation of HHLA2 expression remains poorly understood. A better understanding of HHLA2 regulation in tumor cells and the tumor microenvironment is crucial for the successful translation of these therapeutic agents into clinical applications., Methods: Flow cytometry and quantitative real-time PCR were used to analyze HHLA2 expression in primary kidney tumors ex vivo and during in vitro culture. HHLA2 expression in A498 and 786-O ccRCC cell lines was examined in vitro and in subcutaneous tumor xenografts in NSG mice. Monocytes and dendritic cells were analyzed for HHLA2 expression. We tested a range of cytokines and culture conditions, including hypoxia, to induce HHLA2 expression., Results: Analysis of HHLA2 expression revealed that HHLA2 is expressed on tumor cells in primary kidney tumors ex vivo; however, its expression gradually diminishes during a 4-week in vitro culture period. A498 and 786-O ccRCC tumor cell lines do not express HHLA2 in vitro, but HHLA2 expression was observed when grown as subcutaneous xenografts in NSG immunodeficient mice. Induction experiments using various cytokines and culture conditions failed to induce HHLA2 expression in A498 and 786-O tumor cell lines in vitro. Analysis of HHLA2 expression in monocytes and dendritic cells demonstrated that only IL-10 and BMP4, along with IL-1β and IL-6 to a lesser extent, modestly enhanced HHLA2 protein and mRNA expression., Conclusions: HHLA2 expression is induced on kidney cancer cells in vivo by a tumor microenvironmental signal that is not present in vitro. HHLA2 expression is differentially regulated in kidney cancer epithelial cells and monocytes. Cytokines, particularly IL10, that induce HHLA2 expression in monocytes fail to upregulate HHLA2 expression in tumor cell lines in vitro. These findings underscore the importance of the interplay between tumor cell and tumor microenvironmental signals in the regulation of HHLA2. Further investigation is warranted to elucidate the mechanisms involved in HHLA2 regulation and its implications for therapeutic development., (© 2023. The Author(s).)

Background: The adherence to home exercise is generally low despite its well-known effect on knee osteoarthritis. Therefore, we developed a home exercise application, LongLifeSupport, to provide patients with daily basic exercise videos and an automatic recording calendar. We hypothesized that this application would encourage patients to exercise and help maintain their motivation; this pilot study aimed to determine their exercise adherence rates. Using outcome measures, we also aimed to determine the effect of home exercise using this application and the factors for its continuation., Methods: Twenty patients with knee osteoarthritis were included. The participants exercised for 12 weeks. Using pre- and post-tests, we examined their satisfaction with continuation (only in the post-test), Japanese knee osteoarthritis measure score, short physical performance battery score, bilateral knee extension muscle strength, and short test battery for locomotive syndrome. Furthermore, we investigated correlations between adherence rates and pretest scores of Japanese knee osteoarthritis measure and short test battery and between pretest scores and variations in Japanese knee osteoarthritis measure and short test battery., Results: The mean adherence rate was 82.4%. The participants showed ease of continuation (100%) and significant improvements in the degree of knee pain, pain, and stiffness, and daily life conditions using the Japanese knee osteoarthritis measure score, total score, walk seconds, and chair stand seconds of the short physical performance battery, as well as the extension muscle strength of the right- and pain-side knee. No significant correlations were identified between the adherence rate and the pretest or variation., Conclusion: The adherence rate to the application was over 80%. Participants with knee osteoarthritis showed almost full satisfaction, reduced pain, and improved physical ability. Therefore, the use of this application provided a safe exercise program and maintained the exercise motivation of participants. Thus, it may be useful for unsupervised home exercise., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Total hip arthroplasty (THA) using a minimally invasive (MI) approach is a commonly performed procedure, and several approaches are now being used clinically. The MI anterolateral (MIAL) approach is one of the MI approaches used in clinical practice. Whether the MIAL approach is superior to non-MI approaches remains controversial. To resolve this controversy, we performed a systematic review and a meta-analysis of results of THA procedures that used the MIAL approach. We assessed whether the MIAL approach was superior to the lateral transmuscular (LT) approach in terms of operative time, operative blood loss, radiological parameters, and clinical outcomes., Methods: We performed a methodical search for all literature published on PubMed, Web of Science, and the Cochrane Library, and pooled data using the RevMan software. A p value < 0.05 was considered statistically significant. We calculated the mean differences (MD) for continuous data with 95% confidence intervals (CI) for each outcome., Results: This meta-analysis included 6 studies. Pooled results indicated no statistically significant differences between the groups in terms of operative time (MD = 5.13, 95% CI -2.49 to 12.75, p = 0.19), cup abduction angle (MD = 1.64, 95% CI -1.32 to 4.60, p = 0.28), and cup anteversion angle (MD = 0.75, 95% CI -1.09 to 2.59, p = 0.43). Operative blood loss was significantly greater in those who underwent THA via the MIAL approach than those who underwent THA via the LT approach (MD = 68.01, 95% CI 14.69 to 121.33, p = 0.01). The postoperative Harris hip score (HHS) assessed at the time of final follow-up was significantly higher in those who underwent THA via the MIAL approach than those who underwent THA via the LT approach (MD = 1.41, 95% CI 0.50 to 2.33, p = 0.002)., Conclusion: We conclude that the MIAL approach is superior to the LT approach in terms of clinical outcomes., Level of Evidence: Level Ⅱ., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Background: The modified Stoppa (MS) approach is an alternative to the ilioinguinal (IL) approach and three meta-analyses comparing these two approaches for the treatment of acetabular fractures were published previously. The aim of this study was to provide an updated systematic review and meta-analysis comparing the MS approach with the IL approach for the treatment of acetabular fractures and to answer the following question: are the results of the MS approach superior to those of the IL approach in terms of reduction quality, operative time, operative blood loss, complications, and clinical outcomes for treatment of acetabular fractures?, Patients and Methods: An updated systematic literature review was conducted using relevant original studies from various databases (PubMed, Web of Science and the Cochrane Library). Pooling of data was performed using RevMan software (version 5.3, Cochrane Collaboration, Oxford, UK). A p-value of<0.05 was considered to be significant. We calculated the mean differences (MDs) for continuous data and odds ratio (OR) for dichotomous data with 95% confidence intervals (CIs) for each outcome. Statistical heterogeneity was assessed based on I 2 using the standard Chi 2 test. When I 2 >50%, significant heterogeneity was assumed and a random-effects model was applied for the meta-analysis. A fixed-effects model was applied in the absence of significant heterogeneity., Results: Six studies were included in this meta-analysis. The findings demonstrated that the rate of anatomical reduction was significantly higher in the MS approach than in the IL approach (I 2 =0%, OR=1.75, 95% CI: 1.13-2.69, p=0.01), the operative time was significantly shorter in the MS approach than in the IL approach (I 2 =88%, MD=-63.60, 95% CI: -93.01 - (-34.20), p<0.0001) and operative blood loss was significantly lower in the MS approach than in the IL approach (I 2 =75%, MD=-350.51, 95% CI: -523.45 - (-177.58), p<0.0001). There was no significant difference in the rate of nerve injury (I 2 =0%, OR=0.47, 95% CI: 0.16-1.39, p=0.17), the rate of vascular injury (I 2 =0%, OR=0.51, 95% CI: 0.17-1.49, p=0.22), the rate of infection (I 2 =0%, OR=0.53, 95% CI: 0.25-1.12, p=0.10), the rate of heterotopic ossification (I 2 =45%, OR=0.63, 95% CI: 0.22-1.85, p=0.40), and the rate of excellent or good clinical score (I 2 =21%, OR=1.15, 95% CI: 0.56-2.38, p=0.70) between the two approaches., Discussion: The MS approach provided better reduction quality, shorter operative time, lower operative blood loss, although there were no significant differences in the rate of complications, and excellent or good clinical score between the two approaches., Level of Evidence: III., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Introduction: Haploinsufficiency of A20 (HA20) is a form of inborn errors of immunity (IEI). IEIs are genetically occurring diseases, some of which cause intestinal dysbiosis. Due to the dysregulation of regulatory T cells (Tregs) observed in patients with HA20, gut dysbiosis was associated with Tregs in intestinal lamina propria., Methods: Stool samples were obtained from 16 patients with HA20 and 15 of their family members. Infant samples and/or samples with recent antibiotics use were excluded; hence, 26 samples from 13 patients and 13 family members were analyzed. The 16S sequencing process was conducted to assess the microbial composition of samples. Combined with clinical information, the relationship between the microbiome and the disease activity was statistically analyzed., Results: The composition of gut microbiota in patients with HA20 was disturbed compared with that in healthy family members. Age, disease severity, and use of immunosuppressants corresponded to dysbiosis. However, other explanatory factors, such as abdominal symptoms and probiotic treatment, were not associated. The overall composition at the phylum level was stable, but some genera were significantly increased or decreased. Furthermore, among the seven operational taxonomic units (OTUs) that increased, two OTUs, Streptococcus mutans and Lactobacillus salivarius , considerably increased in patients with autoantibodies than those without autoantibodies., Discussion: Detailed interaction on intestinal epithelium remains unknown; the relationship between the disease and stool composition change helps us understand the mechanism of an immunological reaction to microorganisms., Competing Interests: KH is a scientific advisory board member of Vedanta Biosciences and 4BIO CAPITAL. YK is an employee of JSR Corporation. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Toyofuku, Takeshita, Ohnishi, Kiridoshi, Masuoka, Kadowaki, Nishikomori, Nishimura, Kobayashi, Ebato, Shigemura, Inoue, Suda, Hattori, Morio, Honda and Kanegane.)

Background: Stepladders are used to work at heights in daily life, but their structure and usage differs from that of a ladder; stepladders can fold and stand without support, whereas ladders cannot fold and, thus, require support from other objects. We hypothesised that this difference made ladder and stepladder fall injuries to differ in characteristics. To clarify this hypothesis, we performed a retrospective cohort study on the stepladder fall injuries and compared their characteristics with that of ladder fall injuries., Materials and Methods: We conducted a retrospective cohort study of injuries sustained from either ladder or stepladder falls. In this study, data were retrieved from the computerised database of Teikyo University Chiba Medical Center. Patients admitted to the orthopaedic department because of injury from ladder or stepladder fall were included. The following data were retrieved from the patient records: sex, age, height, body weight, body mass index (BMI), injury severity score (ISS), season, number of injury sites, details of injury and treatment option., Results: One hundred thirty-two patients were included in this study. 101 patients were injured from stepladder falls, and 31 patients were injured from ladder falls. The number of females sustaining injuries due to a stepladder fall was significantly higher than those due to a ladder fall. The most frequent type of injury after fall from stepladder was fracture (48.9%), whereas the most frequent type of injury after fall from ladder was contusion/sprain (56.4%). The most frequently injured body part from stepladder fall was lower extremity (32.6%). In contrast, the most frequently injured body part due to a ladder fall was spine (27.3%)., Conclusion: The current study found that the number of females sustaining injuries due to a stepladder fall was significantly higher than those due to a ladder fall. Furthermore, the most frequent body parts that needed surgery following a ladder fall injury were spine and upper extremity, whereas the most frequent body parts that needed surgery following a stepladder fall injury was lower extremity. Our study indicated that stepladder falls cause severe injuries and physical disability and can be a huge financial burden., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Hematopoietic cell transplantation (HCT) is a curative therapy for patients with severe combined immunodeficiency (SCID). Here, we conducted a nationwide study to assess the outcome of SCID patients after HCT in Japan., Methods: A cohort of 181 SCID patients undergoing their first allogeneic HCT in 1974-2016 was studied by using the Japanese national database (Transplant Registry Unified Management Program, TRUMP)., Results: The 10-year overall survival (OS) of the patients who received HCT in 2006-2016 was 67%. Umbilical cord blood (UCB) transplantation was performed in 81 patients (45%). The outcomes of HCT from HLA-matched UCB (n = 21) and matched sibling donors (n = 22) were comparable, including 10-year OS (91% vs. 91%), neutrophil recovery (cumulative incidence at 30 days, 89% vs. 100%), and platelet recovery (cumulative incidence at 60 days, 89% vs. 100%). Multivariate analysis of the patients who received HCT in 2006-2016 demonstrated that the following factors were associated with poor OS: bacterial or fungal infection at HCT (hazard ratio (HR): 3.8, P = 0.006), cytomegalovirus infection prior to HCT (HR: 9.4, P = 0.03), ≥ 4 months of age at HCT (HR: 25.5, P = 0.009), and mismatched UCB (HR: 19.8, P = 0.01)., Conclusion: We showed the potential of HLA-matched UCB as a donor source with higher priority for SCID patients. We also demonstrated that early age at HCT without active infection is critical for a better prognosis, highlighting the importance of newborn screening for SCID., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Epstein-Barr virus-associated post-transplant lymphoproliferative disorder (EBV-PTLD) is increasingly recognized as a life-threatening complication after transplantation. Most areas affected by EBV-PTLD are lymph nodes, with occasional reports of extranodal lesions such as the gastrointestinal tract and central nervous system; however, orbital regions are extremely rare. We report a case of EBV-PTLD in a cord blood transplant recipient with a tumor in the upper right eyelid. Ultimately, eye symptoms were the first signs of PTLD. Transplant physicians should consider the possibility of PTLD when encountering an orbital lesion., (© 2020 Wiley Periodicals LLC.)

ABO-incompatible hematopoietic stem cell transplantations (HSCTs) are widely practiced; however, the delay in erythrocyte engraftment can be problematic. While erythrocyte engraftment is usually indicated by an increase in reticulocyte levels without the need for erythrocyte transfusions, the disappearance of recipient-derived anti-A/B isoagglutinin and detection of donor-derived A/B antigens can also be used as other parameters. We conducted a retrospective analysis of 68 ABO-incompatible HSCTs, focusing on major and bidirectional mismatch. We analyzed known clinical risk factors associated with delayed erythrocyte engraftment using the three parameters (disappearance of anti-A/B isoagglutinin in recipient, detection of donor-derived A/B antigen, and reticulocyte levels >1%). Although the three parameters were well correlated, the results showed heterogeneity when analyzing the associated risk factors for delayed erythrocyte engraftment. In the analysis of all cases, the requirement for an HLA-matched platelet transfusion was a common risk factor. Furthermore, erythrocyte engraftment was slower in adults than in children. In adults, cytomegalovirus antigenemia was a risk factor for two parameters; however, in children, underlying disease was a common risk factor for all parameters. There is a complex relationship between erythrocyte engraftment and various factors related to HSCTs. Our results suggest that greater accuracy is possible by using analysis methods other than the measurement of reticulocyte levels., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Multiple myeloma (MM) cells are derived from mature B cells based on immunoglobulin heavy chain (IgH) gene analysis. The onset of MM is often caused by a reciprocal chromosomal translocation (cTr) between chr 14 with IgH and chr 11 with CCND1. We propose that mature B cells gain potential to transform by reprograming, and then chromosomal aberrations cause the development of abnormal B cells as a myeloma-initiating cell during B cell redifferentiation. To study myeloma-initiating cells, we have already established normal B cell-derived induced pluripotent stem cells (BiPSCs). Here we established two BiPSCs with reciprocal cTr t(11;14) using the CRISPR/Cas9 system; the cleavage site were located in the IgH Eμ region of either the VDJ rearranged allele or non-rearranged allele of IgH and the 5'-upsteam region of the CCND1 (two types of BiPSC13 with t(11;14) and MIB2-6 with t(11;14)). Furthermore, p53 was deleted using the CRISPR/Cas9 system in BiPSC13 with t(11;14). These BiPSCs differentiated into hematopoietic progenitor cells (HPCs). However, unlike cord blood, those HPCs did not differentiated into B lymphocytes by co-culture with BM stromal cell. Therefore, further ingenuity is required to differentiate those BiPSCs-derived HPCs into B lymphocytes.

Background: Precise implant alignment is a crucial prognostic factor for successful outcomes following total hip arthroplasty (THA). A portable accelerometer-based navigation (PN) device may achieve the same accuracy as that achieved by the computer-assisted navigation surgery technique, with the convenience of a conventional technique. Although the usefulness of PN in THA (PN-THA) has been reported, whether it is more accurate than performing THA with a conventional technique (CON-THA) remains controversial. The difference in surgical time between PN-THA and CON-THA is also unclear. Therefore, we conducted a systematic review and meta-analysis of studies comparing results of PN-THA with those of CON-THA. We focused on the following question: is PN-THA superior to CON-THA in terms of radiological parameters and surgical time?, Patients and Methods: A literature search was conducted in PubMed, Web of Science, and Cochrane Library, to identify studies that met the following inclusion criteria: randomised controlled trials (RCT) or non-RCT, studies involving patients who underwent PN-THA and patients who underwent CON-THA, studies including data on radiological parameters and surgical outcomes. Author names, publication year, country, study design, surgical approach, demographic characteristics of the participants (diagnosis, gender, age, and body mass index), and surgical outcomes (the radiological parameters and the surgical time) were extracted. We calculated the mean differences (MDs) for continuous data with 95% confidence intervals (CIs) for each outcome. p<0.05 was considered significant., Results: Three studies were included in this meta-analysis. The meta-analysis showed that absolute deviation of the postoperative measured angles from the target position for the cup anteversion was significantly smaller in PN-THA than in CON-THA (MD=-1.70, 95% CI=-2.91 to -0.50, [p=0.005]). There was no significant difference in the absolute deviation of the postoperative measured angles from the target position for cup abduction between the groups (MD=-1.82, 95% CI=-4.32-0.67, [p=0.15]). The surgical time was significantly longer in PN-THA than in CON-THA (MD=8.58, 95% CI=4.05-13.10, [p=0.0002])., Discussion: This systematic review and meta-analysis of studies comparing the results of PN-THA with those of CON-THA showed that the PN-THA is advantageous for precise cup implantation compared to CON-THA, although PN-THA has a longer surgical time compared to CON-THA., Level of Evidence: III., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)