Effect of maturation at birth on the clinical features of neonatal cow's milk protein allergy: A retrospective study.

Neonatal immune regulation transitions from fetal immunity and varies with maturation status, but its role in neonatal cow's milk protein allergy (CMPA) remains unknown. We studied the association between maturation status at birth and neonatal CMPA. Clinical and laboratory data of neonates presenting with CMPA symptoms were retrospectively collected from two tertiary hospitals. Patients were assessed according to gestational age at birth: preterm, late-preterm, and full-term. Fifty-five infants (26 females, 14 preterm, 15 late-preterm, and 26 full-term) were included; 44 were negative for milk-specific immunoglobulin E. Neonatal CMPA was common during moderately premature periods. Preterm infants exhibited longer latency from initial CM exposure to disease onset, lower incidence of bloody stool, and absence of elevated monocyte counts. However, immunoreactivity to CM antigens was retained in all infants. Neonatal CMPA features varied with infant maturation status at birth. Our results improve the understanding of intestinal immunity development, fetal/neonatal immune regulation, and CMPA pathogenesis.

Social networking service messages improve novice trainees' motivation and performance of skills.

PURPOSE: We examined the usefulness of positive social networking service (SNS) messages to improve motivation and performance during off-the-job training. METHODS: Subjects were sixth-year medical students who completed a 4-week clinical clerkship in our department involving two separate tasks. Time taken to perform the tasks was recorded on Days 1, 14, and 28. All trainees voluntarily practiced the task until Day 14. The trainees were classified into two groups according to the results of their time measurements on Day 14. The slow time group was intervened with SNS messages (SNS group) and the fast time group was not intervened (non SNS group, nSNS). The SNS group received messages from the moderator daily or every other day. The time to complete the skills practiced in the first (Days 1-14) and second half (Days 15-28) were recorded for each group. RESULTS: On Day 14, the time for both tasks of the nSNS group was significantly faster than the SNS group. However, there was no significant time difference on Day 28. During Days 15-28, the SNS group had significantly more practice days than the nSNS group (5.3 vs. 3.8 days, p = .023). On questionnaire, all SNS group participants indicated that the messages increased their motivation to practice. CONCLUSIONS: SNS messages using smartphones might have increased motivation for task training and improved the performance of tasks in off-the-job training for novice trainees.

Lifetime Follow-Up of a Patient with Metastatic Prostate Cancer Undergoing Multiple Surgical Resections: A Case Report.

BACKGROUND Prostate cancer (PC) often metastasizes after primary resection, and long-term survival following surgical removal of multiple pulmonary metastases is rare. We present a case of a surgeon who demonstrated long-term survival after overcoming repeated surgical challenges for multiple pulmonary metastases from PC. CASE REPORT Twenty-six years ago, a 62-year-old man initially reported discomfort during urination. A prostate examination revealed mildly elevated prostate-specific antigen (PSA) levels. Six months later, PC was diagnosed, and a radical prostatectomy was performed, revealing moderately differentiated adenocarcinoma but no vessel infiltration. At 9 years after the operation, three 10-mm nodules were detected in the right lung. Then, surgical biopsy by wedge pulmonary resection revealed metastatic PC, and therefore, right lower lobectomy including all nodules was planned. Although postoperative maintenance with luteinizing hormone-releasing hormone agonists kept the low PSA levels for 3 years, other newly limited metastases were observed in the opposite left lung, necessitating more surgeries of partial left lung resection. Six years later, a third lung metastasis was detected, as well as mild increases in the tumor size and PSA level, and the patient died 26 years after the initial PC intervention because of malnutrition for 1 year after sustaining bone compression fractures due to a fall, and not due to PC progression. CONCLUSIONS Repeated surgical resections for slow-growing metastatic pulmonary PC was an alternative treatment that facilitated favorable survival and a good quality of life for 26 years in the present case.

Ventilator-induced diaphragmatic dysfunction in extremely preterm infants: a pilot ultrasound study.

To investigate the development of diaphragmatic dysfunction in ventilated extremely preterm infants (EPI) using diaphragm ultrasound (DU). EPI of less than 28 weeks' gestational age who required mechanical ventilation within six hours of birth were included in this prospective, observational study. DU was performed once a day until four days of life. End-inspiratory and end-expiratory thicknesses of the diaphragm were measured, and the diaphragm thickening fraction was calculated. A total of 20 EPI were enrolled. After intubation, there was a progressive reduction in end-inspiratory thickness of the diaphragm from baseline to day 1 (P < 0.001), but not from day 1 to day 2 (P = 0.092), day 2 to day 3 (P = 1.0), or day 3 to day 4 (P = 1.0). There was also a significant reduction in the diaphragm thickening fraction from baseline to day 1 (P < 0.001), but not from day 1 to day 2 (P = 1.0), day 2 to day 3 (P = 1.0), or day 3 to day 4 (P = 1.0).    Conclusions: This study provides the first evidence of diaphragmatic dysfunction in ventilated EPI. We demonstrated a rapid progression of ventilator-induced diaphragmatic dysfunction, with a significant reduction in diaphragm thickness and thickening fraction within 24 h of ventilation. What is Known: • Over-assistance of the ventilator suppresses respiratory effort and induces diaphragm unloading, resulting in diaphragm atrophy or dysfunction. • Diaphragmatic dysfunction contributes to prolonged ventilator dependence and poor clinical outcomes. What is New: • Most extremely preterm infants develop diaphragmatic dysfunction after intubation within 24 hours. • Diaphragm thickness and contraction ability measured by ultrasound would be important indicators of worsening breathing or respiratory outcomes.

Successful Treatment With Everolimus for Multifocal Lymphangioendotheliomatosis With Thrombocytopenia in an Infant.

Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a rare disease characterized by the presence of multiple cutaneous lesions and bleeding from the gastrointestinal tract with thrombocytopenia. Because of the varied phenotypes and rarity of MLT, a treatment strategy has not been standardized thus far. We describe a case of infantile MLT that did not respond to treatment with propranolol, prednisolone, or vincristine. We successfully treated the patient with everolimus, an inhibitor of the mammalian target of rapamycin. Our case provides the first evidence of the effectiveness of everolimus for the treatment of MLT.

Diagnosis and management of neonatal respiratory distress syndrome in Japan: A national survey.

BACKGROUND: Respiratory distress syndrome (RDS) is characterized by a lack of lung surfactant; therefore, biochemical evidence of surfactant deficiency is needed to diagnose RDS. European guidelines recommend surfactant administration when patients need fraction of inspired oxygen exceeding 0.3 on continuous positive airway pressure or intubation. We hypothesized that the European guidelines for surfactant administration were not adopted in Japan because of the lack of RDS diagnosis. This study aimed to investigate neonatologists' attitudes and practices regarding the diagnosis and management of RDS in Japan. METHODS: A mail-based survey regarding the diagnosis and management of RDS was conducted at 111 level III or ΙV neonatal intensive care units in Japan. The questionnaire was completed by the person in charge of each unit. RESULTS: The overall response rate for the questionnaire was 91% (101/111 centers). All respondents referred to chest radiography, and the majority (83%) of respondents referred to stable microbubble rating (SMR) for establishing the diagnosis of RDS. Surfactant administration was chiefly based on clinical conditions, chest radiography, and/or SMR. Most units in Japan do not adopt the European criteria for surfactant administration. CONCLUSION: In Japan, chest radiography and/or SMR are commonly used for the diagnosis of RDS and as the rationale for surfactant administration. Further studies from other countries are required to establish the ideal criteria for surfactant administration.

Number of Examined Lymph Nodes as a Risk Factor for Recurrence in pT1N+ or pT2-3N0 Gastric Cancer.

BACKGROUND/AIM: Japanese Gastric Cancer Treatment Guidelines do not recommend adjuvant chemotherapy after radical gastrectomy for pathological stage (p) T1N+ or pT2~3N0 gastric cancer. However, some patients experience disease recurrence. This study aimed to identify the risk factors for recurrence in pT1N+ or pT2-3N0 gastric cancer. PATIENTS AND METHODS: The study included 157 patients with diagnosed pT1N+ or pT2-3N0 gastric cancer who underwent radical gastrectomy at our institution between January 2001 and December 2020. Clinicopathological data and surgical data were obtained. Independent prognostic factors were analyzed using a Cox proportional hazards regression model. RESULTS: Thirteen patients (8.3%) experienced disease recurrence. Multivariate analysis revealed that the number of examined lymph nodes was an independent prognostic factor for recurrence-free survival (hazard ratio=10.90; 95% confidence interval=1.39-85.86; p=0.023). The group with ≤35 examined lymph nodes had significantly worse recurrence-free survival compared with the group with ≥36 examined lymph nodes (80.7% versus 98.7%; p=0.0005). CONCLUSION: The number of examined lymph nodes (≤35) was an independent risk factor for recurrence after radical gastrectomy with pT1N+ or pT2-3N0 gastric cancer.

Gravity-induced loss of aeration and atelectasis development in the preterm lung: a serial sonographic assessment.

OBJECTIVE: To assess the impact of gravity and time on the changes in the distribution patterns of loss of aeration and atelectasis development in very preterm infants. STUDY DESIGN: Preterm infants less than 32 weeks gestation were included in this prospective, observational study. Infants were assessed via serial lung ultrasound (LUS) score in four lung zones, performed on days 7, 14, 21, and 28 after birth. RESULT: Eighty-eight patients were enrolled. There was a significant main effect of gravity (P < 0.001) and time (P = 0.01) on the LUS score between gravity-dependent lungs and non-dependent lungs. Moreover, there was a significant main effect of gravity (P = 0.003) on atelectasis development between the lungs. CONCLUSION: Gravity and time have an impact on the changes in the distribution patterns of gravity-induced lung injuries in preterm infants.

Lung Ultrasound for Predicting the Respiratory Outcome in Patients with Bronchopulmonary Dysplasia.

OBJECTIVE: This study aimed to investigate the utility of lung ultrasound (LUS) with whole chest scanning for predicting respiratory outcomes in patients with bronchopulmonary dysplasia (BPD). STUDY DESIGN: We performed a prospective observational study. Preterm infants of less than 32 weeks' gestational age requiring oxygen therapy at 28 days of life were included. LUS was performed on day 28, at 36 weeks' postmenstrual age, and at the time of discharge. Each lung was divided into three regions by the anterior and posterior axillary lines and received an LUS score of 0 to 3 points; the total score was obtained by adding the six regional scores. The classification of BPD was determined based on the National Institute of Child and Human Development. The outcomes of this study were the development of moderate-to-severe BPD and the need for home oxygen therapy (HOT). RESULTS: We enrolled 87 patients; 39, 33, and 15 infants had mild, moderate, and severe BPD, respectively. The LUS score correlated with BPD severity and exhibited an improvement trend with time toward the point of discharge. LUS at 28 days of life predicted moderate-to-severe BPD with an area under the curve of 0.95 (95% confidence interval: 0.91-0.99) and HOT with an area under the curve of 0.95 (95% confidence interval: 0.81-1.0). CONCLUSION: LUS with whole chest scanning is useful for predicting respiratory outcomes in patients with BPD, as well as for understanding BPD severity or clinical improvement trends. KEY POINTS: · LUS predicts respiratory outcomes in patients with BPD.. · LUS indicates BPD severity.. · LUS can show clinical improvement with time..

Healthcare for children depend on medical technology and parental quality of life in Japan.

BACKGROUND: The aim of this study was to explore and clarify the healthcare service utilization of children dependent on medical technology (CMT), and the parental health-related quality of life (HRQOL). METHODS: Participants recruited the primary caregivers of children with medical complexity (CMC), identified using an existing registry of raising CMC aged 1-20 years and receiving reimbursements for their home-based medical care at a children's hospital. We used an exploratory cross-sectional study design and sent questionnaires to 286 parents. To clarify the characteristics of CMT and families, we compared two groups on demographics of children's and families', service utilization and parental HRQOL. The participants were categorized into the CMT and children with chronic conditions (CCC) groups, based on whether they required ventilator, suctioning, or tube feeding; had tracheostomy, or gastrostomy; or had central line or clean intermittent catheterization. RESULTS: Of the 95 children selected, 31 were CMT. The participants' characteristics, service utilization, and the parents' HRQOL were compared between the two groups. Compared to CCC, CMT were more likely to be younger, more unstable, more demanding of their caregiver's time, caused greater reductions in their caregiver's sleep time, caused heavier caregiver burden, had higher rates of unexpected hospital admissions and emergency visits, required greater care coordination, and exhibited a higher health service utilization. Parents of CMT were found to have poor mental and physical health in HRQOL. CONCLUSIONS: Improving the outcomes of parents caring for CMT requires high quality healthcare services, especially respite care for the parents, and care coordination.

A novel case of congenital hepatic arterio-veno-portal shunts with umbilical vein aneurysm.

A term male infant presented with congenital hepatic arterio-veno-portal shunts. A mass-like lesion in the left lobe of the liver received blood supply from not only the umbilical vein, but also the hepatic and inferior intrahepatic arteries, communicating with the hepatic and portal veins in a complicated manner, with an umbilical vein aneurysm. The blood flow of the arterio-veno-portal shunts spontaneously and gradually declined from the neonatal period to six years of age. Although mild high-output cardiac failure had developed, no life-threatening events or health problems originating from portosystemic shunts, such as pulmonary artery hypertension and hepatopulmonary syndrome, were observed. However, this report shows that scrupulous follow-up to identify pulmonary artery hypertension and hepatopulmonary syndrome should be continued because complete resolution of the arterio-veno-portal shunts was not obtained in this case.

Nationwide survey of late-onset hemolysis in very low birthweight infants.

BACKGROUND: In Japan, some cases of late-onset acute hemolysis in very low birthweight (VLBW) infants have been reported. These cases had common features but the cause of hemolysis was unknown. The incidence and prognosis of this disease are also unknown. However, there are only few reports of such hemolytic episodes in countries other than Japan. Thus, this study aimed to examine the incidence and clinical course of late-onset acute hemolysis and to establish it as a new disease concept. METHODS: A nationwide prospective survey was conducted from 2011 to 2015 as a rare disease surveillance project of the Japan Society for Neonatal Health and Development. RESULTS: Twenty-four cases were confirmed. The median (range) gestational age, birthweight, and onset of hemolytic episodes were 26 weeks and 2 days (23 weeks and 4 days-31 weeks and 2 days), 898 g (627-1,416 g), and 19 days after birth (9-33 days), respectively. Phototherapy, blood transfusion, and exchange transfusion were required in 22 (96%), 24 (100%), and 7 (29%) cases, respectively. During the observation period, no recurrence of the hemolytic episode occurred. All patients survived; however, one case developed kernicterus and suffered severe neurological sequelae. CONCLUSIONS: In this study, at least 1 out of 1,259 VLBW infants developed hemolysis at 9-33 days after birth in Japan. Owing to the risk of kernicterus, this disease should be recognized as among the important pathological conditions of VLBW infants, suggesting the need to manage jaundice and anemia until 5 weeks after birth.

Care coordination for children with medical complexity in Japan: Caregivers' perspectives.

BACKGROUND: Little is known about the provision of care coordination to children with medical complexity (CMC) and their families in Japan. The aim of this study was to describe provision of care coordination and explore the factors associated with quality of care coordination for Japanese CMC and their families. METHODS: We used an exploratory cross-sectional study design. Participants were recruited at a children's hospital located in one prefecture, Japan. Primary caregivers raising children aged between <1 and 20 years and receiving reimbursements for their home-based medical care at a children's hospital were eligible to participants in this study. The study examined the relationship between parents' ratings of care coordination as 'adequate,' 'inadequate' or 'not received' and characteristics of children, parents, and families. RESULTS: Ninety-nine parents caring for CMC were included in the analysis. Of those, 22.2% reported their child had a care coordinator. Caregivers were divided into three groups depending on the quality of care coordination: Group 1 reported adequate care coordination; Group 2 reported inadequate care coordination; and Group 3 had no need for care coordination. We compared the socio-demographics of children, parents and families, their service use and the health-related quality of life (HR-QOL) and caregiver burden scores of parents across the three groups. The parents' free time, access to timely care for children and service satisfaction were positively associated with adequate care coordination for CMC and their families. CONCLUSIONS: Providing adequate care coordination for CMC and their families is essential for access to timely services and more positive psychological health of parents. High quality care coordination for CMC and their families is urgently needed in Japan.

Ideal endotracheal tube insertion depth in neonates with a birthweight less than 750 g.

BACKGROUND: Appropriate management of the endotracheal tube (ETT) insertion depth is important. The depth calculated using Tochen's formula is overestimated in extremely-low- birthweight infants, particularly those with a birthweight <750 g. Gestational age has been shown to be particularly useful in the Neonatal Resuscitation Program, 7th edition.5 However, a randomized trial for estimating the ETT insertion depth failed to show the advantage of using gestational age over birthweight.6 Therefore, we aimed to estimate the appropriate ETT insertion depth in neonates weighing <750 g. METHODS: This was a single-center, retrospective observational study including neonates weighing <750 g who required intubation. The appropriate depth was determined by adjusting the distance between the actual ETT position and the area from the first to the second thoracic vertebra on the radiograph. Correlations between gestational age and physique were investigated using Pearson's correlation coefficient. We examined small-for- gestational-age (SGA) infants and non-SGA infants separately. RESULTS: Forty neonates were enrolled in this study. The mean gestational age and birthweight were 26.3 weeks and 620 g respectively. Twenty infants were SGA. The ETT position was deep in 35 of 40 cases, with the strongest correlation between weight and ETT insertion depth. The correlation with gestational age was not observed in this study. CONCLUSIONS: Our study showed that the ideal ETT insertion depth at birth correlates with birthweight in neonates weighing <750 g. Therefore, determination by gestational age may not be feasible in populations with a high proportion of SGA infants.

Diaphragm ultrasound examination for congenital diaphragmatic eventration in two premature neonates.

Congenital diaphragmatic eventration (CDE) is always diagnosed by fluoroscopic examination. However, this technique is inappropriate for premature neonates because of risks of transport, hypothermia and ionising radiation. Herein, we describe two cases of premature neonates suspected to have CDE on radiography. We could not perform fluoroscopic examination due to their prematurity status. Therefore, we performed ultrasound examination and succeeded in diagnosing CDE without any risks. Using ultrasound examination, we could evaluate movement and thickness of the diaphragm. We consider this additional information useful for CDE diagnosis. This is the first report on CDE diagnosis using ultrasound examination.

Ultrasonographic confirmation of endotracheal intubation in extremely low birthweigh infants - secondary publication.

BACKGROUND: The purpose of this study was to investigate the usefulness of ultrasonography (US) for confirmation of endotracheal tube (ETT) placement during resuscitation in extremely low birthweight (ELBW) infants. METHODS: We conducted a retrospective review of the medical records of ELBW infants in whom ETT position was verified using US between June 2016 and September 2017. We investigated the backgrounds of the patients and US investigators, and the time required for the detection of exhaled carbon dioxide using the colorimetric method and US. RESULTS: Eleven ELBW infants were evaluated using US by four neonatologists. The median duration required to determine the ETT position by the colorimetric method and US were 11 s and 3 s, respectively. In six ELBW infants, we were able to verify the ETT position more rapidly using US than using the colorimetric method, and were able to perform prompt resuscitation. Unnecessary reintubations were avoided in three ELBW infants. CONCLUSION: Ultrasonography allowed the swift confirmation of the tracheal intubations. The colorimetric method yielded false negative results; in such cases, unnecessary reintubation could have been avoided if US was used. We assessed the mechanism of false negative results and performed appropriate resuscitation.

Resection of liposarcoma of the greater omentum: A case report and literature review.

INTRODUCTION: Liposarcoma usually occurs in the retroperitoneum and limbs. Liposarcoma of the greater omentum is rare, and most information of such liposarcomas has come from case reports. PRESENTATION OF CASE: A 60-year-old woman was found to have an 8-cm intra-abdominal mass (suspected lipoma) by computed tomography. At the age of 63 years, she underwent a medical examination and a mass was palpated in the abdomen. Contrast-enhanced computed tomography and magnetic resonance imaging confirmed the presence of a huge intra-abdominal tumor with the omental artery passing through the mass. The tumor was simply resected. Histopathologically, the tumor was diagnosed as a well-differentiated liposarcoma, and the resection margin was microscopically negative. The patient had developed no recurrence or complications 9 months postoperatively. DISCUSSION: Liposarcoma of the greater omentum is rare, and differentiation of liposarcoma from other tumors is challenging. Adjuvant therapy has not been established as an effective treatment, and radical (R0) resection of the tumor is recommended. Our case of liposarcoma of the greater omentum was surgically managed with good outcomes. CONCLUSION: The diagnosis of liposarcoma with a lipomatous tumor is challenging, and resection should be considered for huge intra-abdominal lipomatous tumors.

Unusual Course of Scimitar Syndrome Preceded by Lung Hypoplasia.

In patients with Scimitar syndrome, right pulmonary artery hypoplasia is considered to lead to right lung hypoplasia because of decrease in blood flow. However, there are no reports wherein the change was actually detected. Thus, the exact developmental mechanism of right pulmonary artery hypoplasia and right lung hypoplasia in patients with Scimitar syndrome is unclear. We experienced a case of Scimitar syndrome preceding right lung hypoplasia, and right pulmonary artery hypoplasia gradually revealed with time. We hypothesized that, in our patient, the lung hypoplasia led to pulmonary artery hypoplasia due to decrease in blood flow. If there are no differences in the diameter of the left and right pulmonary artery in patients with Scimitar syndrome at birth, we propose the necessity of careful observation due to the possibility that pulmonary artery hypoplasia may develop in the future.

Schuurs-Hoeijmakers syndrome in two patients from Japan.

Schuurs-Hoeijmakers syndrome is a rare disease characterized by intellectual disability and dysmorphic facial features among various physical abnormalities due to PACS1 mutation. To date, 28 patients with a recurrent de novo PACS1 mutation (c.607C > T) have been reported, primarily in Western populations. Here, we describe two Japanese patients with Schuurs-Hoeijmakers syndrome with a recurrent PACS1 mutation. In addition to the typical clinical symptoms, each patient presented novel clinical phenotypes. One patient presented with involuntary movements and was treated with trihexyphenidyl hydrochloride. We hypothesized that the PACS1 mutation leads to an inherent dopaminergic insufficiency that underlies the developing symptoms along with the neurodevelopmental processes. The second patient was diagnosed with lipomyelomeningocele during an examination for severe constipation at the age of 2 years and 8 months. The diagnosis of lipomyelomeningocele in this patient was delayed due to the lack of cutaneous lesions. As the majority of patients with PACS1 mutation present constipation, underdiagnosis of lipomyelomeningocele is a possibility. As the phenotypic expansion of the patients with Schuurs-Hoeijmakers syndrome was not fully recognized, additional studies are needed to clarify the clinical spectrum.