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.

Objective: To examine the clinical significance of elevated C-reactive protein (CRP) levels in cases of severe fever with thrombocytopenia syndrome (SFTS), with a particular focus on their role in predicting outcomes beyond that of previous reports.Patients and Methods: CRP values and SFTS case data retrieved from a PubMed search were extracted for analysis. For comparison, the subjects were divided into two groups based on their CRP levels: normal (CRP ≤0.3 mg/mL) and elevated (CRP >0.3 mg/dL).Results: Forty-four cases were identified: 25 with normal CRP levels and 19 with elevated CRP levels. In an univariate analysis, no significant differences were observed between the two groups with respect to age, sex, date of blood examination, white blood cell count, outcome, or lactate dehydrogenase, alanine transaminase, creatine, or ferritin levels. However, the normal group contained a higher proportion of women, and the incidence of other infectious diseases was relatively low.Conclusion: In cases of SFTS, a CRP level >0.3 mg/dL in the first collection indicates the potential for a mixed infection other than an SFTS-associated infection and male prevalence. Further prospective studies are necessary to confirm whether the findings of the present study are generalizable among patients with SFTS.

Objective: Bevacizumab maintenance therapy following platinum-based combination chemotherapy for metastatic, recurrent, or persistent cervical cancer is not recommended as standard therapy. This pilot study aimed to evaluate the efficacy and safety of bevacizumab maintenance therapy and the contribution of the platinum-free interval to the efficacy of subsequent chemotherapy for advanced cervical cancer. Methods: We retrospectively identified 115 patients with metastatic, recurrent, or persistent cervical cancer treated with platinum-paclitaxel chemotherapy plus bevacizumab at 7 institutions between 2015 and 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS) in patients who received bevacizumab maintenance therapy and those who did not. We also analyzed the adverse events associated with bevacizumab and survival time from the start of subsequent chemotherapy in both groups. Results: Following platinum-paclitaxel plus bevacizumab chemotherapy, 34 patients received bevacizumab maintenance therapy and 81 patients did not. Of the 115 patients, 56 received chemotherapy for subsequent relapse. Although bevacizumab maintenance therapy prolonged PFS (median of 16.0 months vs. 9.0 months, p=0.041), significant differences were not observed in OS (p=0.374). Furthermore, bevacizumab maintenance therapy did not prolong OS and PFS after the start of subsequent chemotherapy (p=0.663 and p=0.136, respectively). Bevacizumab maintenance therapy significantly increased hypertension (p=0.035) and proteinuria (p=0.005) but did not cause complications leading to death. Conclusion Bevacizumab single-maintenance therapy for advanced cervical cancer can be considered in selected cases, such as those with acceptable bevacizumab-related side effects. The outcomes of our study will likely contribute to decision-making regarding practical treatment strategies.

Introduction  NPO Japan Heart opened a children’s medical center in Cambodia in 2018 to treat pediatric cancer. In many public hospitals in Cambodia, patients’ meals must be prepared by their families with little knowledge about hygiene and nutrition, so patients may not always receive sufficient nutrition for their treatment. We considered a hygienic and nutritious diet essential for effective pediatric cancer treatment.  Therefore, the “Japan Heart Children’s Medical Center Meal Project” was launched. The objectives of this study were as follows; (1) to describe that patients receive hygienic and nutritious meals during their hospitalization and after discharge, (2) to measure the effects of providing hospital meals and nutrition education by Cambodian staff who are not qualified dietitians, and to clarify the changes in the nutritional status of pediatric cancer patients as a result of these activities.Methods  The target group was pediatric cancer patients and their families.  Japanese dietitians and chefs conducted study sessions, created menu standards based on the Minimum Dietary Diversity (MDD) , and trained local staff to provide meals and nutrition education.   To provide hospital meals, local staff conducted hygiene management, prepared menus based on standards, and measured eating rates. They also provided nutrition education to the patients and their families, and connected survey before and after education. Nutrition assessment was conducted based on WHO Growth Chart BMI for age by measuring height and weight.Results  The MDD achievement rate for the menu increased from 72% to 100% (after intervention 1week-2 week (January, 2020)), and the eating rate increased from 45.9% to a maximum of 80.5% (April, 2020-January, 2022). Surveys before and after nutrition education showed that 89.1% of patient families improved their knowledge and awareness. Height and weight were assessed by BMI, and the percentage of patients with ≤−2SD decreased from 28.1% at admission to 15.9% at discharge.  Conclusions  In Cambodia where there is no dietitian system, it is important to do activities with contents that is feasible for local staff who have never studied nutrition.  In order to further support treatment from the nutritional aspect, it is desirable to develop nutritional human resources in Cambodia.

Purpose: The aim of this study was to evaluate the short-term outcome of physiotherapy in patients with acetabular labral tears and to assess the effectiveness of physiotherapy according to the severity of the labral tear. Materials and Methods: Thirty-five patients who underwent physiotherapy for treatment of symptomatic acetabular labral tears were enrolled. We evaluated the severity of the acetabular labral tears, which were classified based on the Czerny classification system using 3-T MRI. Clinical findings of microinstability and extraarticular pathologies of the hip joint were also examined. The International Hip Outcome Tool 12 (iHOT12) was use for evaluation of outcome scores pre- and post-intervention. Results: The mean iHOT12 score showed significant improvement from 44.0 to 73.6 in 4.7 months. Compared with pre-intervention scores, significantly higher post-intervention iHOT12 scores were observed for Czerny stages I and II tears (all P<0.01). However, no significant difference was observed between pre-intervention and post-intervention iHOT12 scores for stage III tears (P=0.061). In addition, seven patients (20.0%) had positive microinstability findings and 22 patients (62.9%) had findings of extra-articular pathologies. Of the 35 patients, eight patients (22.9%) underwent surgical treatment after failure of conservative management; four of these patients had Czerny stage III tears. Conclusion The iHOT12 score of patients with acetabular labral tears was significantly improved by physiotherapy in the short-term period. Improvement of the clinical score by physiotherapy may be poor in patients with severe acetabular labral tears. Determining the severity of acetabular labral tears can be useful in determining treatment strategies.

Objectives: To evaluate the efficacy of tegafur–uracil (UFT), a prodrug of 5-fluorouracil, plus cisplatin and dexamethasone in patients with docetaxel-refractory prostate cancers.

Methods: Twenty-five patients with docetaxel-refractory prostate cancer were administered oral UFT plus intravenous cisplatin (UFT-P therapy) and dexamethasone. Treatment responses were assessed monthly via prostate-specific antigen (PSA) level measurements. Treatment-related adverse events and overall survival were also assessed.

Results: UFT-P therapy resulted in decreased PSA levels in 14 (56%) patients and increased PSA levels in 11 (44%). In patients with increased PSA levels, 7 (64%) of the 11 patients displayed decreased PSA doubling times. The UFT-P therapy response rate was 84% (21/25 patients). Imaging studies revealed that tumor shrinkage during UFT-P therapy occurred in 1 patient in whom bilateral hydronephrosis caused by lymph node metastasis improved. The median survival time from docetaxel initiation was 36 months. In UFT-P-treated patients, the median PSA progression and overall survival times were 6 and 14 months, respectively. UFT-P treatment-related adverse events were mild diarrhea, general fatigue, and anorexia. Treatment was not discontinued for any of the patients. UFT-P therapy did not cause serious hepatic or renal dysfunction or pancytopenia.

Conclusions: UFT-P therapy is a safe and effective treatment for patients with docetaxel-refractory prostate cancer, although large-scale, multicenter, prospective studies are needed to validate these findings.

We developed pancreatic and duodenal homeobox1 (Pdx1) knockout mice to improve a compensatory hyperinsulinemia, which was induced by hyperplasia in the beta cells or Langerhans' islands, as the diabetic model mice. For targeting of Pdx1 gene by homologous recombination, ES cells derived from a 129(+Ter)/SvJclxC57BL/6JJcl hybrid mouse were electroporated and subjected to positive-negative selection with hygromycin B and ganciclovir. As these results, one of the three chimeric mice succeeded to produce the next or F1 generation. Then, the mouse fetuses were extracted from the mother's uterus and analyzed immunohistologically for the existence of a pancreas. The fetuses were analyzed at embryonic day 14.5 (E14.5) because Pdx1 knockout could not alive after birth in this study. Immunohistochemical staining revealed that 10 fetuses out of 26 did not have any PDX1 positive primordium of the pancreas and that the PDX1 expresses in both the interior and exterior regions of intestine. In particular, one the exterior of the intestine PDX1 was expressed in glands that would be expected to form the pancreas. The result of PCR genotyping with extracted DNA from the paraffin sections showed existence of 10 Pdx1-knockout mice and corresponded to results of immunostaining. Thus, we succeeded to establish a Pdx1-knockout (Pdx1-/-) mice.
Animals ; DNA ; Fetus ; Ganciclovir ; Homologous Recombination ; Hygromycin B ; Hyperinsulinism ; Hyperplasia ; Intestines* ; Islands ; Mice ; Mice, Knockout* ; Pancreas ; Paraffin ; Parturition ; Polymerase Chain Reaction ; Uterus

Stentless bioprosthetic valves have been implanted for treatment of aortic valve disease, especially in elderly patients ; these valves have the advantage of durability and excellent hemodynamics compared with stented bioprosthetic valves. Although good long-term results in patients with stentless bioprosthetic valves have been reported recently, reoperation has been gradually increasing. We performed reoperation for the SJM Toronto SPV and Medtronic Freestyle valves in one patient each. The SJM Toronto SPV was used in a 30-year-old woman ; however, 8 years later, the valve showed severe calcification and adhesions, and could not be completely removed (Case 1). The other reoperation case, wherein a 69-year-old man underwent aortic valve replacement with the Medtronic Freestyle 4 years previously, showed no adhesion around the implanted valve, which could be easily removed from the autologous aortic annulus. Consequently, the first patient required reimplantation of a small mechanical valve (SJM #19). In contrast, we were able to use a stentless bioprosthetic valve (Prima Plus #23) for the second patient. Further observations on stentless bioprosthetic valves are required.

Endoscopic ultrasonography (EUS) combines endoscopy and intraluminal ultrasonography, and allows imaging with a high-frequency transducer over a short distance to generate high-resolution ultrasonographic images. EUS is now a widely accepted modality for diagnosing pancreatobiliary diseases. EUS-guided fine-needle aspiration (EUS-FNA) using a curved linear-array echoendoscope was initially described more than 20 years ago, and since then many researchers have expanded its indications to sample diverse lesions and have also used it for various therapeutic purposes. EUS-guided biliary drainage (EUS-BD) is one of the therapeutic procedures that has been developed using a curved linear-array echoendoscope. Technically, EUS-BD includes rendezvous techniques via transesophageal, transgastric, and transduodenal routes, EUS-guided choledochoduodenostomy (EUS-CDS), and EUS-guided hepaticogastrostomy (EUS-HGS). Published data have demonstrated a high success rate, albeit with a comparatively high rate of nonfatal complications for EUS-CDS and EUS-HGS, and a comparatively low success rate with a low complication rate for the rendezvous technique. At present, these procedures represent an alternative to surgery or percutaneous transhepatic biliary drainage (PTBD) for patients with obstructive jaundice when endoscopic biliary drainage (EBD) has failed. However, these procedures should be performed in centers with extensive experience in linear EUS and therapeutic biliary ERCP. Large prospective studies are needed in the near future to establish standardized EUS-BD procedures as well as to perform controlled comparative trials between EUS-BD and PTBD, between rendezvous techniques and direct-access techniques (EUS-CDS and EUS-HGS), and between EBD and EUS-BD.
Biopsy, Fine-Needle ; Cholangiopancreatography, Endoscopic Retrograde ; Choledochostomy ; Dioxolanes ; Drainage ; Endoscopy ; Endosonography ; Fluorocarbons ; Humans ; Jaundice, Obstructive ; Transducers

This paper proposes a method for evaluating and scoring the activities of rehabilitation service users in order to pinpoint the problems with the health service of this kind and set the adequate targets for each user. Sincs the Nursing Care Insurance System was introduced in Japan in 2000, it has been argued that home-visit rehabilitation services should be excluded from home-nursing care services. However, the methods of certifing that nursing care is required are not fully established yet for setting the rehabilitation targets for service users. As things stand, it is recommended that such a method as the Functional Independence Measure (FIM) or the Barthel Index (BI) should be utilized. However, these methods only evaluate “performing activities” (the activities that a user usually performs). In order to set the users' targets, we thought it necessary to establish a method for evaluating “possible activities” (the activities that a user is able to perform at his/her full capacity). We have established a method called Functional Scoring (FS) which evaluates and scores the both performing and possible activities based on the same evaluation items. We conducted experimental evaluations on the home-visit rehabilitation users for one year from October 2005 to September 2006. When the first evaluations in 2005 were compared with the second evaluations in 2006, the total score of the performing activities significantly increased from 44.1±13.7 to 47.8±14.2 (P<0.05). Although the total score of the possible activities did not significantly increase, it demonstrated an upward trend from 49.6±13.2 to 51.6±13.5. The result suggests that our method is useful for distinguishing between the performing and possible activities. The proposed method enables us to adequately recognize the problems each user has, and to set the rehabilitation target for each user, which can be shared between the user, care personnel, and care service provider.
Rehabilitation aspects ; Functional ; FS ; Care given by nurses ; Published Comment