Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an anti-inflammatory molecule that negatively regulates the non-canonical nuclear factor-κB pathway. Although TRAF3 haploinsufficiency (TRAF3 HI) can influence innate and adaptive immune cells, its effect on inflammatory bowel disease (IBD) development remains unclear. Here, we report the first case of severe early-onset IBD with a novel TRAF3 variant leading to HI, successfully treated with ustekinumab. A 6-year-old girl with a recurrent parotitis, otitis media, tonsilitis, and atopic dermatitis developed IBD involving the stomach, small intestine, and colon. At diagnosis, the immunoglobulin (Ig)G and IgA levels were relatively high, and lymphocyte subsets showed increased counts of plasmablasts, class-switch recombination B cells, and circulating T-follicular helper cells. Treatment with azathioprine and infliximab failed to maintain remission marked by several relapses accompanied by erythema nodosum and arthritis; however, ustekinumab, an anti-interleukin (IL)-12/23p40 antibody, led to long-term clinical remission, normalizing the Ig level and reducing abnormal lymphocyte counts. Whole-exome sequencing revealed a novel heterozygous mutation in TRAF3 [p.(Pro487Leufs*8)], resulting in TRAF3 under-expression. Our case may highlight the contribution of TRAF3 HI to the development of IBD and provide insights into IBD pathophysiology, suggesting the involvement of the IL-12/23-T-follicular helper cell pathway affected by genetic mutations.

BACKGROUND: Building an effective casework system for child maltreatment is a global issue. We estimated the effect of household dysfunction (i.e., interparental violence, caregiver mental health problems, and caregiver substance abuse) on child maltreatment to understand how to advance the current framework of child welfare. METHODS: The sample comprised 759 children (1- to 17-year-old; mean age was 10.6; 404 boys and 355 girls) placed in temporary custody units (one of the strongest intervention of the Japanese child protection system). Caseworkers from 180 units across 43 prefectures completed questionnaires on children and their family and were asked whether a child maltreatment report had been made after cancelation of custody in a 15-month follow-up period. The relations of household dysfunction and maltreatment reports were assessed using the Cox proportional hazard model. RESULTS: About half (48.4%) of the children had been placed in the unit because of maltreatment, and 88.3% had a history of victimization. Seventy-six cases had maltreatment reports after cancelation. We entered household dysfunction variables individually into the model, and each had a significant relationship with maltreatment reports (hazard ratios for interparental violence, caregiver mental health problem, and substance abuse were 1.69, 1.69, and 2.19, respectively) after covariate adjustment. When treating these three variables as cumulative risk score model of household dysfunction, the hazard ratio increased with increasing number of score (1.96 for score two; 2.35 for score three; score 0 as reference). CONCLUSIONS Greater household dysfunction score is a risk of maltreatment after intensive intervention. It is imperative to construct systems facilitating cooperation between child and adult service sectors and to deliver seamless services to children and families. Our findings provide child protect services with risk-stratified interventions for children at victimization risk and promote adult-focused services to be proactive in prevention or intervention for adults with perpetration risk.
Adolescent ; Caregivers ; psychology ; Child ; Child Abuse ; psychology ; statistics & numerical data ; Child Protective Services ; statistics & numerical data ; Child, Preschool ; Domestic Violence ; psychology ; statistics & numerical data ; Family Characteristics ; Female ; Humans ; Incidence ; Infant ; Japan ; epidemiology ; Longitudinal Studies ; Male ; Mental Disorders ; epidemiology ; psychology ; Risk Factors ; Substance-Related Disorders ; epidemiology ; etiology

OBJECTIVES: Endoscopic laryngopharyngeal surgery (ELPS) is a minimally invasive transoral surgery that was developed to treat superficial larygo-pharyngeal cancer, in which a mucosal lesion is resected transorally while preserving deeper structures by subepithelial injection. The purpose of this retrospective study is to evaluate voice outcome in patients who underwent ELPS for superficial hypopharyngeal cancer. As important structures in producing voice, such as intrinsic laryngeal muscles, their fascia, and recurrent laryngeal nerve, are located in the medial side of the piriform sinus and the postcricoid region of the hypopharynx, we focused on patients with cancer lesions involving these regions. METHODS: From April 2010 to March 2011, 25 consecutive patients with superficial laryngopharyngeal cancer were treated with ELPS at Kyoto University Hospital. Among the 25 patients, 11 patients with cancer lesions on the medial side of the piriform sinus or the postcricoid area were studied. Preoperative and postoperative voice functions including maximum phonation time (MPT), mean flow rate (MFR), jitter, shimmer, soft phonation index (SPI), and noise-to-harmonic ratio (NHR), were compared retrospectively. RESULTS: Five of 11 cancer lesions had submucosal invasion and no lesion had invaded the muscular layer pathologically. T stage was classified as Tis in 5 cases, T1 in 4 cases, and T2 in 2 cases. All lesions involved the medial side of the piriform sinus and 2 also involved the postcricoid area. Vocal fold movement was normal in all cases after the surgery. Average preoperative and postoperative values for MPT, MFR, jitter, shimmer, SPI, and NHR, were 22.7 seconds and 23.4 seconds, 165 mL/sec and 150 mL/sec, 1.53% and 1.77%, 3.82% and 5.17%, 35.5 and 36.6, and 0.13% and 0.14%, respectively. There was no statistical difference between preoperative and postoperative data for all values examined. CONCLUSION: ELPS is useful in preserving voice function in the treatment of superficial hypopharyngeal cancer. Preserving the deeper structures including intrinsic muscles and their fascia may be important for preserving voice function as long as the lesions are superficial.
Fascia ; Humans ; Hypopharyngeal Neoplasms* ; Hypopharynx ; Laryngeal Muscles ; Muscles ; Narrow Band Imaging ; Phonation ; Pyriform Sinus ; Recurrent Laryngeal Nerve ; Retrospective Studies ; Vocal Cords ; Voice*

Dengue is an emerging disease in Nepal and was first observed as an outbreak in nine lowland districts in 2006. In 2010, however, a large epidemic of dengue occurred with 4,529 suspected and 917 serologically-confirmed cases and five deaths reported in government hospitals in Nepal. The collection of demographic information was performed along with an entomological survey and clinical evaluation of the patients. A total of 280 serum samples were collected from suspected dengue patients. These samples were subjected to routine laboratory investigations and IgM-capture ELISA for dengue serological identification, and 160 acute serum samples were used for virus isolation, RT-PCR, sequencing and phylogenetic analysis. The results showed that affected patients were predominately adults, and that 10% of the cases were classified as dengue haemorrhagic fever/ dengue shock syndrome. The genetic characterization of dengue viruses isolated from patients in four major outbreak areas of Nepal suggests that the DENV-1 strain was responsible for the 2010 epidemic. Entomological studies identified Aedes aegypti in all epidemic areas. All viruses belonged to a monophyletic single clade which is phylogenetically close to Indian viruses. The dengue epidemic started in the lowlands and expanded to the highland areas. To our knowledge, this is the first dengue isolation and genetic characterization reported from Nepal.

We reviewed 24 cases of patchplasty for true thoracic aortic aneurysm performed in our hospital up to July 2001. The size of the aneurysm in the ascending aorta was 6.0cm (1 case), and the mean size in the aortic arch was 2.5±0.5cm (4 cases), that in the distal arch was 4.7±1.7cm (11 cases), and that in the descending aorta was 3.7±0.5cm (8 cases). The hospital mortality rate was 12.5% (3 patients out of 24). The causes of death were multiple organ failure, cerebral bleeding and sepsis. In the long-term results, 2 patients had recurrence, but there were no late deaths in relation to the aneurysmal recurrence. We performed open stent operations for severe adhesion and pulmonary dysfunction in the aneurysmal recurrence cases. The postoperative course of these cases was uneventful. The open stent was useful for the treatment of the aneurysmal recurrence in the distal arch.

A 62-year-old man was admitted to our hospital because of acute aortic dissection (DeBakey type III b). Inflammatory findings were detected and methicillin-resistant staphylococcus aureus (MRSA) was detected by blood culture. Appropriate antibiotic therapy was begun but was ineffective. Repeated CT scans revealed dilation of the false lumen with thrombus and perianeurysmal inflammatory change in the lung. A diagnosis of infected aortic dissection was made. The patient was treated by resection of the descending aorta and placement of an in situ Dacron graft covered with a pedicled omental flap. An infected thrombus in the false lumen was confirmed by a positive MRSA culture. Computed tomography was found to be more sensitive in the diagnosis of infected aortic dissection. When the infection is not controlled with antibiotics, prompt surgical treatment should be performed.

During 23 years, 224 cases underwent graft replacement of thoracic aortic aneurysms at our institution. Of these, 14 cases suffered postoperative vascular graft infection. Out of the 14 cases, 13 cases had sternal or mediastinal infections, and one case showed sepsis without these deep wound infections. Six cases were positive by blood culture. We thought that sternal or mediastinal infections had a high possibility of contamination of vascular grafts and that cases with these deep wound infections should be treated as cases of graft infection. Reoperation was done urgently soon after the diagnosis of infection was made. When the wound was not so deep, only debridement was performed. In addition to debridement, continuous irrigation through a chest tube and, recently, pedicled omental flap placement were done, when the wound was deep. Except for the one case without deep wound infection, 13 cases were reoperated. There were 4 hospital deaths; 3 operated cases and the nonoperated case, due to lack of control of their infection. Blood culture were positive in all these four cases. The other 10 cases were discharged from hospital without infection. Infection of vascular grafts after operation for thoracic aortic aneurysms is a serious complication and urgent reoperation should be done. However it should be noted that the mortality rate of cases with positive blood culture is high.

Twenty-two patients who underwent vascular reconstruction for carotid occlusive disease by April 1998 were examined in terms of long-term results. The cause of disease was atherosclerosis in 16, and aortitis in 6. The operation method included CEA in 11 and bypass in 5 cases in the atherosclerosis cases, and CEA in 2 and bypass in 6 cases in aortitis. Cases of occlusive disease included 1 early occlusion (atherosclerosis) and 4 late occlusion (atherosclerosis 2, aortitis 2). The cause of early occlusion was considered to be due to technical factors, but late occlusion was thought to be related to progression of disease, anastomotic intimal thickening, and recurrence of inflammation. It is important to enforce strict operative indications, accurate intraoperative monitoring, and perioperative drug control.

A 26-year-old man was suffered a tendon injury in the left knee when playing American football 3 years previously and was treated consevatively. He was admitted to our hospital because of coldness and paresthesia in the left leg since 2 months previously. Femoral angiogram revealed severe stenosis of left popliteal artery and occlusion of the anterior and posterior tibial artery. CT and MRI examination revealed a tumor which protruded into the lumen of the left popliteal artery or dissection of left popliteal artery. Operation was performed by a posterior approach. The left popliteal artery was not compressed from the lateral side and there was a white thrombus in the popliteal artery. Thromboendartherectomy and autologus venous patch plasty was done. Histopathological findings of the stenotic lesion revealed an organizing thrombus, chiefly consisting of fibrin, and intima both of which were infiltrated by granuration tissue. It was suggested that the stenotic lesion was caused by arterial wall hyperplasia or thrombus formation during the healing process after blunt arterial injury. The post-operative course was uneventful.

A rare case of juxtarenal aortic occlusion due to Takayasu's arteritis is reported. A 46-year-old man who had been suffering from intermittent claudication from the age of 44 when Buerger's disease was suspected at another hospital because of exacerbation of the symptom. Occlusion of the abdominal aorta and severe aortic wall thickness were identified by the abdominal CT scan. After the improvement of inflammation, under the diagnosis of juxtarenal aortic occlusion due to inflammatory disease, we performed an aortobifemoral bypass grafting using a Y-shaped prosthesis (proximal anastomosis was end-to-end) found a tight inflammatory adhesion around the abdominal aorta. Histopathological examination of the resected specimen revealed an infiltration of lymphocytes, plasma cells in aortic media and adventitia, severe fibrosis in the aortic adventitia, and a diagnosis of Takayasu's arteritis was made. The postoperative course was uneventful but we should periodically check for inflammatory signs, and anastomotic aneurysms.