Allogeneic stem cell transplantation for inherited metabolic disorders: 35 years' experience at a single institution.

Hematopoietic stem cell transplants for inherited metabolic disorders performed at Tokai University Hospital between June 5, 1986, and May 28, 2021, were analyzed and compared between the period before 2007 and the period from 2007 onward based on availability of medical resources. Transplants were performed for 38 patients with mucopolysaccharidosis, 33 with adrenoleukodystrophy, and 16 with another disorder. Before 2007, oral busulfan-based regimens were mainly used. From 2007 onward, intravenous busulfan-based regimens or 4 Gy of thoracoabdominal irradiation (TAI), fludarabine, and melphalan (Mel)/treosulfan were adopted. Between 2002 and 2010, adrenoleukodystrophy was treated with 12 Gy of TAI and Mel. HLA-identical sibling bone marrow was used in 43% of cases before 2007 and 15% from 2007 onward, while alternative donors were selected for other transplants. Overall survival and event-free survival (EFS) before 2007 and from 2007 onward were 76% and 62%, and 97% and 85%, respectively (P = 0.006 and 0.017). Transplant era predicted superior overall survival and EFS, while myeloablative conditioning also predicted EFS. The incidence of primary graft failure decreased from 2007 onward, especially in cord blood transplant when 4 Gy of TAI with 150 mg/m2 fludarabine and 180 mg/m2 Mel or 42 g/m2 treosulfan were used as conditioning.

Subcutaneous Panniculitis-like T Cell Lymphoma Diagnosed with a Slowly Progressive Course: A Case Report.

Panniculitis is an inflammation that occurs in subcutaneous adipose tissue. Panniculitis includes physical panniculitis (e.g., traumatic) and infectious panniculitis (e.g., bacterial, fungal, subcutaneous panniculitis-like T cell lymphoma [SPCTL], etc.). Accurate diagnosis is crucial due to similar clinical presentation of all types of panniculitis. Here, we report a case of SPCTL which was initially diagnosed with traumatic panniculitis. A 15-year-old male patient was admitted to a previous hospital due to a progressively enlarged right flank and inguinal mass after an abdominal bruise. He was initially diagnosed with traumatic panniculitis, but the mass expanded throughout the chest and abdomen accompanied by a fever of over 11 months. Computed tomography (CT) revealed a subcutaneous mass in the anterior chest and abdominal wall. Fludeoxyglucose F18 (FDG) uptake was observed at those lesions using FDG-positron emission tomography (PET). A biopsy of the mass lesion was performed, during which SPCTL was diagnosed based on pathological examination. He was initially treated with prednisolone and cyclosporine A for two weeks. His fever went down, but subcutaneous mass in the chest and abdominal wall persisted. Therefore, he received a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen. After 6 courses of CHOP, CT revealed no disease evidence. He remained in complete remission at 30 months of therapy.

Spontaneously Resolved Suspected Hemophagocytic Lymphohistiocytosis or Macrophage Activating Syndrome Associated with Neonatal Lupus Erythematosus: A Case Report.

OBJECTIVES: To present a rare case of neonatal lupus erythematosus (NLE) associated with suspected hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS). CASE PRESENTATION: A female infant weighing 2,995 g was born to a mother without medical history of any disease. At birth, the patient had erythematous papules on her face and trunk. She was admitted at 1 day of age with elevated C-reactive protein levels. The patient was diagnosed with NLE based on the presence of anti-Ro/SSA and anti-La/SSB antibodies. Thereafter, it became clear that the antibody levels in her mother were also elevated. At 20 days of age, the infant showed elevated transaminases, ferritin, triglyceride, and soluble interleukin-2 receptor levels. Although HLH or MAS was suspected, she did not fulfill the diagnostic criteria. Thereafter, these abnormal values spontaneously improved, and the skin rash improved with the use of topical steroids. The patient was discharged at 39 days of age. At 1 year of age, the patient's growth and development were normal. CONCLUSION: NLE should be considered in infants with an unexplained skin rash at birth. When a diagnosis is made, close observation of the infant's clinical features is needed to determine whether they will develop HLH or MAS.

Survival and unique clinical practices of extremely preterm infants born at 22-23 weeks' gestation in Japan: a national survey.

OBJECTIVES: To investigate prognosis and clinical practices of infants born at 22-23 weeks' gestational age (wkGA) in Japan. DESIGN: A national institutional-level electronic questionnaire surveys performed in September 2021. SETTING: All perinatal centres across Japan. PATIENTS: Infants born at 22-23 wkGA in 2018-2020. MAIN OUTCOME MEASURES: Proportion of active resuscitation and survival at neonatal intensive care unit (NICU) discharge, and various clinical practices. RESULTS: In total, 255 of 295 NICUs (86%) responded. Among them, 145 took care of infants born at 22-23 wkGA and answered the questions regarding their outcomes and care. In most NICUs (129 of 145 (89%)), infants born at 22+0 wkGA can be actively resuscitated. In almost half of the NICUs (79 of 145 (54%)), infants born at ≥22+0 wkGA were always actively resuscitated. Among 341 and 757 infants born alive at 22 and 23 wkGA, respectively, 85% (291 of 341) and 98% (745 of 757) received active resuscitation after birth. Among infants actively resuscitated at birth, 63% (183 of 291) and 80% (594 of 745) of infants born at 22 and 23 wkGA survived, respectively. The survey revealed unique clinical management for these infants in Japan, including delivery with caul in caesarean section, cut-cord milking after clamping cord, immediate intubation at birth, hydrocortisone use for chronic lung disease, analgesia/sedation use for infants on mechanical ventilation, routine echocardiography and brain ultrasound, probiotics administration, routine glycerin enema and skin dressing to prevent pressure ulcers. CONCLUSIONS: Many 22-23 wkGA infants were actively resuscitated in Japan and had a high survival rate. Various unique clinical practices were highlighted.

Impact of comprehensive quality improvement program on outcomes in very-low-birth-weight infants: A cluster-randomized controlled trial in Japan.

BACKGROUND: Differences in outcomes among neonatal intensive care units (NICUs) in Japan have been noted, prompting the need for quality improvement. AIM: To assess a comprehensive quality improvement program on outcomes in very-low-birth-weight (VLBW) infants. STUDY DESIGN: A cluster-randomized clinical trial. SUBJECTS: Forty hospitals and VLBW infants born in 2012-2014 and admitted to those hospitals were study subjects. OUTCOME MEASURES: The intervention group (IG) received a comprehensive quality improvement program involving clinical practice guidelines, educational outreach visits, workshops, opinion leader training, audits, and feedback. The control group (CG) was provided only with the guidelines. The primary outcome was survival without neurological impairment at three years of age. RESULTS: IG consisted of 19 hospitals and 1735 infants, while CG included 21 hospitals and 1700 infants. There were no significant differences in gestational weeks, 29.1(26.9-31.3) vs. 29.1(26.7-31.1) or birth weights (g), 1054(789-1298) vs. 1084(810-1309) between the two groups. Both groups showed survival rates without neurological impairment of 67.2 % (1166) and 66.9 % (1137), respectively, without a significant difference. There was no significant difference in mortalities at NICU discharge between the groups, with rates of 4.0 % (70) and 4.2 % (72) respectively. Several clinically relevant improvements were observed in IG, including reduced rates of sepsis, adrenal insufficiency, transfusion for anemia, and a shorter interval to achieve full enteral feeding. However, these did not lead to improvements in the primary outcome. CONCLUSION: The comprehensive quality improvement program to Japanese NICUs did not result in a significant improvement in survival without neurological impairment in VLBW infants.

Reference values for urinary protein, albumin, beta 2-microglobulin, and the alpha 1-microglobulin-to-creatinine ratio in Japanese children.

BACKGROUND: The importance of the ratio of creatinine to urinary protein, albumin, and low-molecular weight protein as a urinary marker in chronic kidney disease patients is widely recognized. However, no reference values have hitherto been established for these markers in Japanese children. The present study aimed to establish the reference values for these urinary markers in Japanese children. METHODS: The first morning urine was randomly collected from 1712 pupils aged ≥ 3 to < 18 years during school and kindergarten mass urinary screenings. The upper limit of the reference values was set at the 97.5th percentile of the creatinine ratio per marker. RESULTS: The urinary protein-to-creatinine ratio (PCR), urinary albumin-to-creatinine ratio (ACR), urinary beta 2-microglobulin-to-creatinine ratio (BMCR), and urinary alpha 1-microglobulin-to-creatinine ratio (AMCR) showed an age-related decrease at the 50th percentile reflecting an age-related increase in urinary creatinine. The appropriate reference value for the PCR and ACR was 0.12 g/gCr and 35 mg/gCr, respectively, in the entire cohort. The appropriate reference value for the BMCR was 0.5 µg /mgCr for age ≥ 3 to < 6 years and 0.35 µg/mgCr for age 6 years or older. The appropriate reference value for the AMCR was 5.0 µg/mgCr for age ≥ 3 to < 6 years and 3.5 µg /mgCr for age 6 years or older. CONCLUSION: The present study was the first to determine appropriate reference values for the PCR, ACR, BMCR, and AMCR based on an analysis of the first morning urine samples of a large number of children.

Postnatal longitudinal analysis of serum Nitric oxide and eosinophil counts in extremely preterm infants.

BACKGROUND: Nitric oxide (NO) may be related to the pathogenesis of several morbidities in extremely preterm infants, including late-onset adrenal insufficiency. However, eosinophilia is observed under pathological conditions with adrenal insufficiency. Therefore, this study explored postnatal changes in NO levels and eosinophil counts in extremely preterm infants with and without morbidities. METHODS: Nineteen extremely preterm infants with a median gestational age of 27.0 weeks and median birth weight of 888 g were enrolled in this study. Serum levels of nitrogen oxides (NOx) and peripheral blood eosinophil counts were measured at birth and every 2 weeks thereafter. Morbidities of the study group were diagnosed using a single criterion. RESULTS: Serum NOx levels (mean ± standard deviation) were 22.5 ± 14.9 µmol/L, 51.2 ± 23.7 µmol/L, 42.4 ± 15.2 µmol/L, and 33.8 ± 9.4 µmol/L at birth and 2, 4, and 6 weeks of age, respectively. The serum NOx level at 2 weeks of age was significantly higher than that at birth and 6 weeks of age. Eosinophil counts, which increase with adrenal insufficiency, were measured simultaneously and were 145 ± 199/µL, 613 ± 625/µL, 466 ± 375/µL, and 292 ± 228/µL at birth and 2, 4, and 6 weeks of age, respectively. These values showed that the eosinophil count was significantly higher at 2 weeks of age than at birth and 6 weeks of age. The serum NOx level of infants without chorioamnionitis was significantly increased at 4 weeks of age, and the eosinophil count of infants with necrotizing enterocolitis was significantly increased at 2 weeks of age. No correlation with the NOx level or eosinophil count was observed in infants with late-onset circulatory collapse. CONCLUSION: The postnatal serum NOx level and eosinophil count were significantly correlated with each other and peaked at 2 weeks of age.

One-step embedding method for maintaining orientation of pathological tissue specimens using agar thin films.

Pathological histology examination involves handling a variety of specimens that are cut according to regulations and placed in cassettes. Tissue fragments in the cassettes are then diagnosed after processing, embedding, thin sectioning, staining and other procedures using a processing machine. Maintaining tissue fragment order and orientation during these processes is important for accurate diagnosis. In this study, we present a method of maintaining tissue fragment order and orientation using a thin film of ultra-high-strength agar and evaluate its usefulness during tissue sectioning.Cassettes were prepared, each containing three pieces of porcine liver, and compared embedding time with and without agar thin films (ATFs). Embedding was performed by three medical laboratory scientists with different levels of experience.To enable one-step tissue sample embedding, ATFs were integrated with samples in the cassettes. This resulted in an average reduction of 6.22 s of embedding time per cassette compared with traditional embedding methods.Through the use of ATFs, tissue fragment order and orientation is maintained, and embedding process time shortened. Additionally, ATFs are easily prepared and stored in 10% neutral buffered formalin over extended periods, allowing for immediate use during sectioning. This method is ideal to implement in busy pathology laboratories.

Successful Emergency Decompressive Laminectomy for Burkitt Lymphoma with Metastatic Spinal Lesions: A Case Report.

Although Burkitt lymphoma (BL) usually arises in the abdomen or pelvis, it can also arise in the epidural space as a primary or secondary site and present with back pain or limb weakness. Emergency management is necessary to relieve spinal cord compression (SCC). Herein, we report a case of BL with metastatic spinal lesions in a 16-year-old female who presented with sudden-onset progressive walking difficulty. She was admitted to a previous hospital where she presented with abdominal pain and vomiting and was diagnosed with intussusception via a computed tomography scan. Laparoscopic small bowel resection was performed, during which a diagnosis of BL was made on the basis of pathological examination. Sudden numbness in the extremities and the complete inability to walk occurred ten days after surgery. Thoracolumbar MRI revealed a metastatic mass extending from C7 to T6 with evidence of SCC. Emergency decompressive laminectomies (from C7 to T6) and partial debulking of the tumor were performed 12 hours after the onset of her neurologic symptoms. She was subsequently treated with chemotherapy, and she made a complete neurologic recovery. Emergency decompressive laminectomies for BL with spinal lesions could effectively lead to the recovery of neurologic symptoms.

X-linked Agammaglobulinemia Diagnosed Following Bezold's Abscess: A Case Report.

Bezold's abscess is an extracranial complication of otitis media, in which a cervical abscess forms from the mastoid process through an ostial fistula, and is a rare condition in recent years. In this study, we experienced a X-linked agammaglobulinemia, which was discovered due to Bezold's abscess. Case: A 12-year-old boy suffering from recurrent right suppurative otitis media for three months was treated with tympanostomy and oral antibacterial therapy at a local otorhinolaryngology clinic. The patient visited the clinic due to a recurrence of symptoms. CT showed bony defects in the cortical bone and mastoid process of the lateral side of the right mastoid cell. The patient was referred to our hospital, admitted the same day and underwent emergency surgery. Intraoperative findings led to the diagnosis of acute mastoiditis and Bezold's abscess c aused b y mastoiditis spreading to the s ternocleidomastoid muscle. After drainage and administration of ABPC/SBT, the abscess disappeared, and the patient's general condition improved. Subsequently, a blood typing test performed on admission suggested the influence of low immunoglobulin levels. A close examination by the pediatric department led to a diagnosis of X-linked agammaglobulinemia. As a result, the patient receives regular immunoglobulin therapy and has been free of infection, including Bezold's abscess. CONCLUSIONS: In the case of recurrent otitis media and rare infections, congenital immune abnormalities should be considered.

Automatic detection of punctate white matter lesions in infants using deep learning of composite images from two cases.

Punctate white matter lesions (PWMLs) in infants may be related to neurodevelopmental outcomes based on the location or number of lesions. This study aimed to assess the automatic detectability of PWMLs in infants on deep learning using composite images created from several cases. To create the initial composite images, magnetic resonance (MR) images of two infants with the most PWMLs were used; their PWMLs were extracted and pasted onto MR images of infants without abnormality, creating many composite PWML images. Deep learning models based on a convolutional neural network, You Only Look Once v3 (YOLOv3), were constructed using the training set of 600, 1200, 2400, and 3600 composite images. As a result, a threshold of detection probability of 20% and 30% for all deep learning model sets yielded a relatively high sensitivity for automatic PWML detection (0.908-0.957). Although relatively high false-positive detections occurred with the lower threshold of detection probability, primarily, in the partial volume of the cerebral cortex (≥ 85.8%), those can be easily distinguished from the white matter lesions. Relatively highly sensitive automatic detection of PWMLs was achieved by creating composite images from two cases using deep learning.

Noninvasive respiratory support following extubation in preterm infants.

The use of noninvasive respiratory support is widespread in newborn infants with respiratory distress. As the use of noninvasive respiratory support has increased, so too have the number of modes available. Among these modes, low-flow nasal cannula and nasal continuous positive airway pressure (NCPAP) have been used for a long time and have known efficacy and safety in newborn infants needing respiratory support. High-flow nasal cannula (HFNC) has been newly introduced, and its efficacy and safety are currently being investigated. Bilevel nasal continuous positive airway pressure and nasal intermittent positive-pressure ventilation are often used when NCPAP or HFNC therapy fails. More recently, noninvasive neurally adjusted ventilatory assist and noninvasive high-frequency oscillatory ventilation have been introduced, and their efficacy and safety are currently under evaluation. Comparison of the efficacy and safety among various modes of noninvasive respiratory support after extubation in preterm infants is helping to clarify the position of each mode. The clarification of the strength and characteristics of each device within the same mode will become important as a future direction of noninvasive respiratory support after extubation in such subjects. However, no research has yet reported on long-term outcomes in preterm infants receiving noninvasive respiratory support after extubation. Therefore, further research is needed to evaluate the long-term outcomes.

Small for Gestational Age Affects Outcomes on Singletons and Inborn Births in Extremely Preterm Infants: A Japanese Cohort Study.

OBJECTIVE: This study aimed to compare the short- and long-term outcomes of extremely preterm small for gestational age (SGA) infants and appropriate for gestational age (AGA) infants in Japan. STUDY DESIGN: We retrospectively assessed 434 SGA and 1,716 AGA infants born at 22 to 27 weeks of gestational age (GA) and examined their outcomes on singletons and inborn births between 2003 and 2012. Infants were followed-up for 3 years, and the clinical characteristics and outcomes were compared. Fisher's exact and Student's t-tests were used for independent sample comparison. Logistic regression was used to identify associated factors. RESULTS: The prevalence of intraventricular hemorrhage ≥ grade 3 was significantly lower (adjusted odds ratio [aOR]: 0.28; 95% confidence interval [CI]: 0.11 - 0.72), and the prevalence of bronchopulmonary dysplasia at 36 weeks of GA and the need for home oxygen therapy were significantly higher (aOR: 2.20; 95% CI: 1.66 - 2.91 and aOR: 2.46; 95% CI: 1.75-3.47, respectively) in SGA infants than in AGA infants. SGA infants born at 24 to 25 weeks of GA had a significantly higher prevalence of developmental quotient (DQ) < 70 (aOR: 1.73; 95% CI: 1.08 - 2.77). Those born at 26 to 27 weeks of GA showed a significantly higher prevalence of cerebral palsy (CP) and visual impairment (aOR: 2.31; 95% CI: 1.22 - 4.40 and aOR: 2.61; 95% CI: 1.21 - 5.61, respectively). CONCLUSION: In SGA infants, birth at 24 to 25 weeks of GA is an independent risk factor for DQ < 70, and birth at 26 to 27 weeks of GA is an independent risk factor for CP and visual impairment. However, we did not consider nutritional and developmental factors, and a longer follow-up would help assess neurodevelopmental outcomes. KEY POINTS: · SGA is a risk factor for poor outcomes.. · In SGA infants, birth at 25 to 26 weeks is a risk factor for low a DQ.. · In SGA infants, birth at 26 to 27 weeks is a risk factor for CP..

Association Between Eosinophilia and Late-onset Circulatory Collapse in Preterm Infants: A case-Control Study.

Late-onset circulatory collapse (LCC) in preterm infants is presumably caused by relative adrenal insufficiency. Because eosinophilia is known to be associated with adrenal insufficiency, we attempted to clarify the relation-ship between eosinophilia and LCC in preterm infants. We divided the cases of the infants (born at < 28 weeks' gestation) admitted to our neonatal intensive care unit in 2008-2010 into 2 groups: those diagnosed with LCC that received glucocorticoids (LCC group), and those who did not receive glucocorticoids (control group). We compared eosinophil counts between the 2 groups and between before and after glucocorticoid treatment in the LCC group. A total of 28 infants were examined: LCC group (n = 12); control group (n = 16). The peak eosin-ophil counts of the LCC group were significantly higher than those of the control group (median: 1.392 × 109/L vs. 1.033 × 109/L, respectively; p = 0.02). Additionally, in the LCC group, the eosinophil counts declined significantly after glucocorticoid treatment (0.877 × 109/L vs. 0.271 × 109/L, p = 0.003). Eosinophil counts in the LCC group were significantly higher than in the control group and decreased rapidly after gluco-corticoid treatment. These results indicate that eosinophilia may be a factor associated with LCC caused by adrenal insufficiency.

Video-based neonatal state assessment method for timing of procedures.

BACKGROUND: Procedures should be performed when an infant is most receptive to disruptions in order to reduce the stress on the infant. However, frequent direct observations place a heavy burden on medical staff. There is therefore a need for a method for quantitatively and automatically evaluating the neonatal state. METHODS: Ten infants in our hospital were enrolled in this study. The states of the infants were assessed by medical staff using the Brazelton Neonatal Behavioral Assessment Scale and were recorded on video at the same time. The recorded states were reclassified as activity levels, a new state classification method that includes middle activity, which is the appropriate time for a procedure. Using image analysis, motions of the infant were quantified as two indices: activity and pause time. Activity and pause time were compared for each activity level. The cutoff values of the indices were calculated, and the sensitivity and specificity of the middle activity were calculated. RESULTS: There was a significant difference between all groups of activity level (P < 0.01). The maximum sensitivity and specificity of middle activity were 71.7% and 51.2%, respectively. CONCLUSIONS: The neonatal state of infants can be quantitatively and automatically evaluated using video cameras, and the activity level can be used to determine an appropriate time for procedures in infants. This will reduce the burden on medical staff and lead to less stressful procedures for infants.

Randomized Controlled Trial of High-Flow Nasal Cannula in Preterm Infants After Extubation.

OBJECTIVES: Our aim is to compare the efficacy and safety of high-flow nasal cannula (HFNC) against those of nasal continuous positive airway pressure (NCPAP) or nasal intermittent positive-pressure ventilation (NIPPV) after extubation in preterm infants. METHODS: This prospective, randomized, noninferiority trial was conducted in 6 tertiary NICUs. Infants born at <34 weeks who needed noninvasive ventilation after extubation were enrolled. We randomly assigned infants to an HFNC group when HFNC was used or to an NCPAP/NIPPV group when NCPAP or NIPPV was used. The primary outcome was treatment failure within 7 days after extubation. We then examined clinical aspects of treatment failure with HFNC use. RESULTS: In total, 176 and 196 infants were assigned to the HFNC and NCPAP/NIPPV groups, respectively. The HFNC group showed a significantly higher rate of treatment failure than that of the NCPAP/NIPPV group, with treatment failure occurring in 54 infants (31%) compared with 31 infants (16%) in the NCPAP/NIPPV group (risk difference, 14.9 percentage points; 95% confidence interval, 6.2-23.2). Histologic chorioamnionitis (P = .02), treated patent ductus arteriosus (P = .001), and corrected gestational age at the start of treatment (P = .007) were factors independently related to treatment failure with HFNC use. CONCLUSIONS: We found HFNC revealed a significantly higher rate of treatment failure than NCPAP or NIPPV after extubation in preterm infants. The independent factors associated with treatment failure with HFNC use were histologic chorioamnionitis, treated patent ductus arteriosus, and a younger corrected gestational age at the start of treatment.