Increase in pediatric complicated appendicitis during the COVID-19 pandemic: a multi-center retrospective study.

PURPOSE: An increase in the incidence of pediatric complicated appendicitis (CA) during the COVID-19 pandemic has been reported in many countries. We investigated how the pandemic has affected Japan. METHODS: We retrospectively reviewed children of ≤ 15 years old treated for acute appendicitis across 5 medical centers during the pandemic period (January to October in 2020), with the pre-pandemic period (January to October in 2017 to 2019) evaluated as a historical control. The incidence of CA and disease characteristics were then compared between the periods. RESULTS: The total number of patients was 55 in 2020 and 192 in 2017-2019. In all centers, the incidence of acute pediatric CA in the pandemic period significantly increased compared to the pre-pandemic period (18.2% vs. 32.7%, p = 0.02). On limiting our evaluation to the 3 institutions with reductions in patient numbers, the incidence of CA increased (16.3% vs. 37.9%, p = 0.01), and the duration of pre-operative symptoms was prolonged (1.3% vs. 1.7 days, p = 0.03). There were no significant differences in the age, sex, white blood cell count, C-reactive protein, or body temperature. No cases were diagnosed with SARS-CoV-2. CONCLUSIONS: The incidence of acute pediatric CA increased during the pandemic period. This may be related to an extended duration of symptoms due to individuals fearing contracting COVID-19 while visiting a hospital.

Genetic Profile and Microsatellite Instability in a Case of Secondary Esophageal Squamous Cell Carcinoma 12 Years After Allogeneic Hematopoietic Stem Cell Transplantation for Aplastic Anemia.

We report on a 16-year-old Japanese boy in whom an esophageal squamous cell carcinoma (ESCC) developed 12 years after allogeneic hematopoietic stem cell transplantation was performed for aplastic anemia. A high frequency of microsatellite instability was detected in samples of ESCC. Moreover, the detection of pathogenic variants, including single nucleotide substitution of TP53 (c.346C>T) and BRCA2 (c.6952C>T) and splicing of KDM6A (c.1194+2T>G), suggest that the development of ESCC in the patient was triggered by impairment of checkpoint and repair for DNA damage and epigenetic modification through accumulation of gene mutations induced by chronic graft-versus-host disease and prolonged administration of tacrolimus.

Surgical management of urachal remnants in children: open versus laparoscopic approach: A STROBE-compliant retrospective study.

Urachal remnants (UR) represent a failure in the obliteration of the allantois, which connects the bladder to the umbilicus, at birth. Surgical management of UR in children is controversial. The traditional surgical approach involves a semicircular intraumbilical incision or a lower midline laparotomy. Recently, many reports have supported the laparoscopic approach (LA) for removing UR. However, there is a paucity of data comparing the benefits of LA those of the open approach (OA).We retrospectively reviewed all children (aged ≤16 years) with UR who underwent surgical procedures. Age at surgery, sex, operative time, intraoperative or postoperative complications, total wound length, and length of hospital stay length after operation were analyzed.Overall, 30 children aged between 9 months and 16 years (mean 9.0 years) underwent surgical procedures: 15 were treated by OA and 15 were treated by LA. The only statistically significant variable was the operative time. Furthermore, we reanalyzed the age distributions of the older children (aged ≥10 years). In this group, no significant difference in the operative time between OA and LA was observed; however, there was a statistically significant difference in the total wound length.Our review indicated that LA required longer operative time than OA without any cosmetic advantage. However, in older children (aged ≥10 years), the difference in the operative time was not significant; moreover, LA provided greater cosmetic advantage. LA is recommended for older children (aged ≥10 years) because of its cosmetic advantage.

Thalidomide potentiates etoposide-induced apoptosis in murine neuroblastoma through suppression of NF-κB activation.

PURPOSE: Treatment for high-risk neuroblastoma is still challenging. The purpose of the present study was to determine whether thalidomide suppresses etoposide-induced NF-κB activation and thus potentiates apoptosis in murine neuroblastoma. METHODS: A murine neuroblastoma cell line, C1300, and A/J mice were used in this study. We evaluated NF-κB activation after using etoposide with or without thalidomide by quantitative analysis of NF-κB by ELISA and by Western blot analysis of IκB phosphorylation in vitro and in vivo. Induction of apoptosis was evaluated by Western blot analysis of the apoptotic signals caspase-3, 8, and 9 in vitro and by TUNEL assays in vivo. We also evaluated the efficacy of the combination of etoposide and thalidomide by assessing tumor growth and mouse survival in vivo. RESULTS: Etoposide activated NF-κB in C1300 cells. This activation was suppressed by thalidomide and IκB was re-upregulated. The apoptotic signals were enhanced by the combination of thalidomide and etoposide compared with etoposide alone in vitro, which was consistent with TUNEL assays. The combination of etoposide and thalidomide also slowed tumor growth and mouse survival. CONCLUSION: Thalidomide potentiates etoposide-induced apoptosis in murine neuroblastoma by suppressing NF-κB.

Risk Factors for Incisional Hernia in Children.

BACKGROUND: Incisional hernia (IH) is a major complication of abdominal surgery. Although previous studies reported that the incidence of IH after abdominal surgery in adults was 5-50% and that various independent risk factors were involved, IH in children is still not well known. The objective of our study was to investigate the incidence and risk factors for IH in children. METHODS: We retrospectively reviewed all children who underwent abdominal surgery at the Jikei University Hospitals (Jikei University Hospital, Kashiwa Hospital, Katsushika Medical Center and Daisan Hospital) between January 2001 and December 2016. Abdominal surgery in children was defined as open laparotomy and laparoscopic abdominal surgery in patients ≤ 15 years old. Conventional open repair for inguinal hernias, umbilical hernia repair, congenital abdominal defect repair and orchiopexy were excluded. RESULTS: Overall, 2049 children were performed abdominal surgery. Among them, 14 children (10 males and 4 females) developed IH, and the incidence of IH was 0.68% (14/2049). There is no significant difference between laparotomy and laparoscopic surgery. The statistically significant variables and identified risk factors were operation in neonates, laparoscopic fundoplication and open supraumbilical pyloromyotomy. In all patients who had IH repair, there was no recurrence during the follow-up period 50.4 months (range 1 months-10 years) except two recurrence cases. CONCLUSION: The incidence of IH in children is significantly lower than that in adults, and the above three risk factors were revealed. Before abdominal surgery, we recommend that pediatric surgeons should mention the risk of developing IH when the patient has the above risk factors.

Periostin as a biomarker for the diagnosis of pediatric asthma.

BACKGROUND: There are some biomarkers for asthma diagnosis but they are often difficult in clinical use, particularly in pediatric cases. Periostin is an extracellular matrix protein, upregulated in response to IL-4 or IL-13. Serum periostin is expected to be used as a non-invasive biomarker for asthma diagnosis and management. METHODS: Twenty-eight children with asthma (BA) and 27 children without asthma (patients with pectus excavatum, etc. as control group) aged 6-16 years were included. Bronchial asthma was diagnosed according to International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Fractional exhaled nitric oxide (FeNO), lung function, blood eosinophil counts, total immunoglobulin E (IgE) levels, and serum periostin levels were assessed. Results were compared between BA and controls. Asthma diagnostic accuracies were calculated using receiver operating characteristics (ROC) curve analyses. RESULTS: Serum periostin levels in the BA group were significantly higher than those in the control group [medians (with interquartile ranges), 134.0 (116.3-166.3) vs. 112.0 (97.0-132.0) ng/ml; p = 0.012]. The area under the ROC curve (AUC) for periostin, FeNO, and eosinophil counts were 0.70, 0.72, and 0.84, respectively. After the exclusion of controls with pectus excavatum, AUC for periostin, forced expiratory volume in 1 s (FEV1 ), and maximum mid-expiratory flow rate (MMF) were 0.75, 0.74, and 0.80, respectively. CONCLUSION: Serum periostin levels were significantly higher in children with asthma. ROC AUC values for periostin were equivalent to conventional biomarkers, including FeNO levels and lung function testing, indicating the utility of serum periostin levels in diagnosing asthma in children.

Paraneoplastic Syndrome of Angiomatoid Fibrous Histiocytoma May Be Caused by EWSR1-CREB1 Fusion-induced Excessive Interleukin-6 Production.

We describe a 7-year-old girl with angiomatoid fibrous histiocytoma (AFH) presenting severe inflammatory symptoms. The cytokine/chemokine profile of serum samples before and after surgery demonstrated that interleukin (IL)-6 had decreased by the greatest percentage. The AFH cells were immunopathologically positive for IL-6 and Tyr705-phosphorylation of signal transducer and activator of transcription 3. The EWSR1-CREB1 fusion gene detected in the tumor leads to continuous activation of CREB1 and IL-6 production, because the promoter region of IL-6 has a CREB binding site. Thus, IL-6 plays pivotal roles in both paraneoplastic syndrome and the oncogenesis of AFH.

Repair of Bochdalek hernia in an adult complicated by abdominal compartment syndrome, gastropleural fistula and pleural empyema: Report of a case.

INTRODUCTION: Bochdalek's diaphragmatic hernia (BDH) rarely developed symptomatic in adulthood but mostly required an operation. In adult BDH cases, long-term residing of the massive intraabdominal organs in the thoracic cavity passively causes loss of domain for abdominal organs (LOD). PRESENTATION OF CASE: A 63-year-old man presented at our institution complaining of sudden left upper quadrant abdominal pain. Chest radiography showed a hyperdense lesion containing bowel gas in the left pleural space. Computed tomography revealed a dilated bowel above the diaphragm and intestinal obstruction suggestive of gangrenous changes. These findings were consistent with the diagnosis of incarcerated BDH and an emergency laparotomy was performed. Operative findings revealed the hypoplastic lung, lack of hernia sac, and location of the diaphragmatic defect, which indicated that his hernia was true congenital. Organs were reduced into the abdominal cavity, and large defect of the diaphragm was repaired with combination of direct vascular closure and intraperitoneal onlay mesh reinforcement using with expanded polytetrafluoroethylene (ePTFE) mesh. On the postoperative day 1, the patient fell into the shock and was diagnosed to have abdominal compartment syndrome (ACS). Conservative therapies were administered, but resulted in gastropleural fistula and pleural empyema, which required an emergency surgery. Mesh extraction and fistulectomy were performed. DISCUSSION: A PubMed search for the case of ACS after repair of the adult BDH revealed only three cases, making this very rare condition. CONCLUSION: In dealing with adult BDH, possible post-repair ACS should be considered.

Delayed primary reconstruction of esophageal atresia and distal tracheoesophageal fistula in a 471-g infant.

INTRODUCTION: Waterston et al. have classified the risk of morbidity in infants with esophageal atresia and tracheoesophageal fistula. However, few cases of esophageal atresia with distal tracheoesophageal fistula in extremely low birth weights infants have been reported. In such infants, the selection of primary reconstruction or staged repair remains controversial. In the present report, we describe the difficulties of perioperative management of such small infants and discuss how to rescue them. PRESENTATION OF CASE: A 471-g female infant was delivered at 28 weeks' gestation via cesarean section. Esophageal atresia with distal tracheoesophageal fistula was diagnosed. Esophageal banding and gastrostomy were performed via laparotomy on day 1. On day 74, when the infant weighed almost 1000g, airway management was discontinued. On day 136, endotracheal intubation again became necessary because of respiratory problems, and the esophagus was reconstructed on day 141. Despite this operation, the patient died on day 276 because of continuing respiratory problems. DISCUSSION: Esophageal banding is considered an appropriate treatment for respiratory problems in such extremely low weight infants. However, the timing of dissection of the tracheoesophageal fistula after esophageal banding is extremely important. CONCLUSION: In the present case, ligation of the tracheoesophageal fistula and esophageal reconstruction should have been performed as soon as possible.

[Diagnosis of mild hemophilia A made by massive intraabdominal bleeding in a 13-year-old boy].

We report a 13-year-old boy who had massive intra-abdominal bleeding without a history of bleeding episodes or traumatic cause of bleeding. The patient underwent surgical treatment because bleeding was not controlled after treatment with tranexamic acid and transfusions including fresh-frozen plasma. Bleeding was traced to the lower left lobe of the liver. The mother's side of the family had a history of bleeding episodes in the boy's grandfather, great uncle, and son of a great aunt. A low level of plasma factor VIII coagulant activity (22%) led to a diagnosis of mild hemophilia A. Compared with severe hemophilia, mild hemophilia is more difficult to diagnose because bleeding episodes are less frequent. Most cases are found after incidental trauma or uncontrolled surgery-related bleeding, there is rarely a family history of hemophilia and activated partial thromboplastin time is normal or slightly prolonged. However, bleeding episodes in mild hemophilia may result in excessive, sometimes life-threatening hemorrhage and require early diagnosis and replacement treatment with adequate amounts of factor VIII, as in severe hemophilia.

Risk factors of infection of implanted device after the Nuss procedure.

PURPOSE: The Nuss procedure is a minimally invasive procedure for the correction of pectus excavatum. It involves insertion of a substernal metal bar. A feared complication of any implantation procedure is infection, which often requires removal of the implanted device. This report describes the authors' experience with infectious complications after the Nuss procedure. METHODS: The study included 195 patients diagnosed with pectus excavatum. We performed the Nuss procedure under thoracoscopic control on all the patients. Factors analyzed for all patients included bar infection, sex, age, number of bars, and season of the year during which the operation was performed. RESULTS: Of the 195 study patients, there were 11 patients who suffered postoperative infectious complications, including 7 patients with cellulitis and 4 patients with bar infections. We removed the infected bars from three of the patients with bar infections. Ten of the patients with infected bar had undergone their operations in the summer. Sex, age and number of bars did not differ significantly between patients with or without infections. However, a significantly higher number of infections occurred among patients who underwent the Nuss procedure in the summer compared with the other seasons of the year (P < 0.05, Kruskal-Wallis Test). CONCLUSION: All patients with cellulitis successfully recovered with conservative treatment. However, 75 % of the patients with bar infections required removal of the infected device. Our study results showed that performance of the Nuss procedure during summer is a risk factor for postoperative infection. We recommend that particularly careful technique must be used during summer to prevent postoperative infections following the Nuss procedure.

Busulfan-conditioned bone marrow transplantation results in high-level allogeneic chimerism in mice made tolerant by in utero hematopoietic cell transplantation.

OBJECTIVE: In utero hematopoietic cell transplantation (IUHCT) is a non-ablative approach that achieves mixed allogeneic chimerism and donor-specific tolerance. However, clinical application of IUHCT has been limited by minimal engraftment. We have previously demonstrated in the murine model that low-level allogeneic chimerism achieved by IUHCT can be enhanced to near-complete donor chimerism by postnatal minimally myeloablative total body irradiation (TBI) followed by same-donor bone marrow transplantation. Because of concerns of toxicity related to even low-dose TBI in early life, we wondered if a potentially less toxic strategy utilizing a single myelosuppressive agent, Busulfan (BU), would provide similar enhancement of engraftment. METHODS: In this study, mixed chimerism was created by IUHCT in a fully allogeneic strain combination. After birth, chimeric mice were conditioned with BU followed by transplantation of bone marrow cells congenic to the prenatal donor. RESULTS: We demonstrate that: 1) low-level chimerism after IUHCT can be converted to high-level chimerism by this protocol; 2) enhancement of chimerism is BU dose-dependent; and 3) BU reduces the proliferative potential of hematopoietic progenitor cells thus conferring a competitive advantage to the non-BU-treated postnatal donor cells. CONCLUSION: This study confirms the potential of IUHCT for facilitation of minimally toxic postnatal regimens to achieve therapeutic levels of allogeneic engraftment.

Complete allogeneic hematopoietic chimerism achieved by in utero hematopoietic cell transplantation and cotransplantation of LLME-treated, MHC-sensitized donor lymphocytes.

OBJECTIVE: In utero hematopoietic cell transplantation (IUHCT) typically achieves low-level mixed hematopoietic chimerism. However, the goal of IUHCT is to achieve therapeutic levels of chimerism. We hypothesized that prenatal adoptive immunotherapy might achieve high-level donor chimerism after IUHCT. MATERIALS AND METHODS: BALB/CE15 fetal mice were transplanted with a mixture of C57BL/6 (B6) T-cell-depleted bone marrow (TCD BM) cells and splenocytes from B6 mice presensitized to BALB/C alloantigen. The splenocytes were preincubated in L-leucyl-L-leucine methyl ester (LLME), to minimize graft vs host disease (GVHD). Recipients were followed after birth for donor cell chimerism and GVHD. RESULTS: Full donor hematopoietic chimerism following a single prenatal transplant was achieved in seven transplanted animals. Fully chimeric animals were healthy, without evidence of GVHD, and maintained their engraftment for the duration of the study (48 weeks). However, the addition of presensitized LLME-treated cells decreased survival until weaning relative to TCD BM alone, suggesting that some animals were lost to acute GVHD. Surviving chimeric animals demonstrated increased frequencies of T-regulatory cell populations in their spleen and BM, suggesting that they had successfully suppressed GVHD, allowing survival. CONCLUSIONS: This study represents "proof in principle" that prenatal immunotherapeutic strategies may achieve complete hematopoietic engraftment across full MHC barriers when combined with IUHCT. However, strategies with greater hematopoietic specificity must be developed prior to consideration of clinical application.

Mixed chimerism following in utero hematopoietic stem cell transplantation in murine models of hemoglobinopathy.

OBJECTIVE: Mixed hematopoietic chimerism after bone marrow transplantation can provide effective treatment for beta-thalassemia because of the selective advantage that exists for donor erythropoiesis. In utero hematopoietic stem cell transplantation (IUHSCTx) can achieve mixed hematopoietic chimerism, particularly when a selective advantage exists for donor cells. To investigate the biology of IUHSCTx in hemoglobinopathies, we performed fully allogeneic IUHSCTx in murine models of beta-thalassemia (Thal) and sickle cell disease (SCD). MATERIALS AND METHODS: We serially assessed and compared levels of mononuclear cell (MNC) and erythroid chimerism after IUHSCTx of either adult bone marrow (BM)- or fetal liver (FL)-derived allogeneic donor cells in the two hemoglobinopathy models, which differ significantly in their degree of anemia (Thal>>SCD) and red cell half-life (Thal<