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.

We report a case of a 53-year-old woman who suffered from persistent tic symptoms around her mouth and right eyelids. She visited our Kampo clinic because of a poor response to Western medicine. We focused on symptoms including palpitations, anxiety symptoms and fullness in the chest and hypochondrium, and prescribed Kampo formulas containing Bupleurum root, which had little effect. Finally, we thought this might be caused by liver qi depression, heart heat, blood stasis, liver blood and yin deficiency as well as liver yang transforming into wind, because she had symptoms of not only fullness in the chest and hypochondrium, but also nocturnal awakening, constipation, a pale red and purple tongue with yellow fur, pressure pain beside her umbilicus, calf pain and fine pulse. Therefore, we administered modified formula of nyoshinsan and shoyosan. Her symptoms have markedly improved after taking this formulation and have been stable for 18 months. In addition, the number of Western medications has been reduced. It is known that some cases of persistent tic disorder are resistant to standard Western treatments. Kampo medicine may be a useful alternative and provide relief in such cases.

  Introduction: Stainless steel needles are mainly used in acupuncture treatment, but material considerations are crucial for patients with metal allergies. This report presents a case of acupuncture treatment administered without inducing allergic symptoms in the patient, achieved through effective collaboration with medical specialists.  Case: The patient was a 35-year-old woman. Complaints were menstrual symptoms, neck and lumbar pain, the former appeared after the birth of her second child at the age of 24, and the latter was felt chronically. She visited our department because she wanted to receive kampo medicine and acupuncture treatment. It was also reported that she had metal allergy symptoms. Therefore, after consultation with the allergist of our department, a full examination was requested at the dermatology department. In the meantime, our department suspected PMS, PMDD, and muscular or joint pain. First, we started acupuncture treatment using titanium press tack needles and resin contact needles to address muscular or joint pain, taking metal allergies into consideration. The frequency was once every two weeks. One month later, a patch test result was positive for nickel. Nevertheless, she still requested acupuncture treatment, and we consulted with the allergist regarding her case. Then, with her consent, the silicone-coated stainless steel acupuncture needles were inserted into the distal part of the limbs and remained in place for 15 min. During this time, we observed her skin and instructed her to closely monitor it and report any changes at her next visit. From the fifth treatment onward, additional acupuncture needles were placed in the neck and lumbar region, all without any allergic symptoms being observed.  Discussion and Conclusion: In this case, acupuncture treatment was performed safely in the medical cooperation. In the future, we would like to further examine the establishment of acupuncture treatment with high safety for patients with metal allergy symptoms and collaboration with medical specialists.

Methods: A total of 209 patients with osteoporosis and 54 with adult spinal deformities were included. Patients were divided into two groups based on pelvic incidence–lumbar lordosis (PI–LL): <20° and ≥20° groups. The sagittal vertical axis (SVA), thoracic kyphosis, PI, pelvic tilt (PT), LL, sacral slope, and pelvic femoral angle (PFA) were measured. Health-related quality of life (HRQOL) was assessed in 86 patients using the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ). A new index, PFA–(PI–LL), was defined as spinopelvic–hip mismatch. Correlation coefficients were calculated for each radiographic parameter, and the coefficient of determination (R2) for the relationship of each parameter with SVA was evaluated in both groups. The correlations between SVA, PT, PI–LL, PFA–(PI–LL), and JOABPEQ domain scores were also analyzed. Results: PI–LL correlated with PFA in the PI–LL <20° group (r=0.56, p<0.001) but not in the PI–LL ≥20° group. Among all parameters, PFA–(PI–LL) demonstrated the strongest association with SVA, indicating its superior ability to explain variations in sagittal alignment in both groups and across all patients (all patients, R2=0.77). Significant correlations were observed between the radiographic parameters and JOABPEQ scores across all domains. Conclusions PFA–(PI–LL), which represented spinopelvic–hip mismatch, was a reliable indicator of hip compensatory function in terms of anterior trunk inclination and HRQOL.

We report a case of a 38-year-old woman who initially had pain in her entire left leg and then began to feel intense pain everywhere in her body. She visited our Kampo clinic because of a poor response to the various drugs prescribed by six doctors over two years. We made the diagnosis of fibromyalgia and suggested Kampo therapy with decoction. We focused on liver qi depression, blood deficiency, and blood stasis because she had symptoms of dry skin, cold feet, deeply located fine pulses, purple tongue with thick yellow fur, fullness in her chest and hypochondrium, and pain on palpation beside her umbilicus. Therefore, we prescribed a keppuchikuoto modified formula with poor effect. Finally, we thought this might be caused by a liver-kidney yin deficiency because she had long-term symptoms and administered a dokkatsukiseito modified formula. Her symptoms markedly improved after taking this formulation. Some cases of fibromyalgia are resistant to standard Western treatments. Kampo medicine may be useful and provide relief in such cases.

Background: No studies have compared the outcomes of direct perineurial suture with vein graft cuff repair and indirect collagen allograft repair of the lingual nerve following an injury. Therefore, we evaluated and compared the outcomes of each over a 1-year observation period. We retrospectively assessed 20 patients who had undergone microneurosurgical repair of unilateral lingual nerve injuries at the Wakayama Medical University Hospital between May 2015 and March 2019. We utilized two different methods for lingual nerve repair, i.e., direct perineurial repair with a vein graft cuff and interpositional collagen allograft repair. Sensory and taste function in the lingual nerve were preoperatively evaluated using a static two-point discrimination test, superficial pain/tactile sensation test, tests for the pressure pain threshold (Semmens-Weinstein monofilament), test for thermal discrimination hot and cold sensation, and a taste discrimination test. These tests were performed again at 6 and 12 months postoperatively. Results: Compared to the preoperative conditions, all patients showed improved sensory reactions. Functional sensory recovery outcomes were defined by Pogrel’s criteria, Medical Research Council Scale grades, and functional sensory recovery. In each group, all patients improved after the operation. However, the operation time was significantly shorter for an interpositional collagen allograft repair as compared to that for a direct perineurial repair with a vein graft cuff. Conclusions There were no statistically significant differences between the two repair Methods, except for the operation time. Both methods led to satisfactory results for all criteria. From an economic point of view, direct perineurial repair with a vein graft cuff is meaningful; however, the esthetic effect on the donor site should be considered. Conversely, interpositional collagen allograft repair has the advantage of a greatly shortened operation time.

We report a case of a 74-year-old woman who suffered from uncomfortable heat under her right shoulder blade and felt anxiety about general fatigue that had been worsening mainly in the summer. She visited our Kampo clinic because of insufficient effect of various types of drug that had been prescribed by 3 doctors for about a year. We made the diagnosis of somatic symptom disorder and suggested Kampo therapy with decoction. We thought this might be caused by liver qi depression, blood deficiency, and blood stasis because he had symptoms of dry skin, cold of feet, deeply located fine pulse, pale and purple tongue with yellow thick fur, fullness in the chest and hypochondrium. Therefore we administered keppuchikuoto modified formula. Her symptom improved within about a month after taking this formulation. There was no recurrence of the physical symptom and fatigue in the summer during taking medicine for about 20 months. Evidence-based treatment in somatic symptom disorder has not been established and some cases are resistant to treatments in modern Western medicine. Kampo medicine may be useful and hopeful.

Background: Arbekacin (ABK) is an aminoglycoside that exhibits anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-Pseudomonas aeruginosa activities. Therefore, for patients with febrile neutropenia (FN) and concurrent pneumonia suspected to be caused by MRSA, ABK may be sufficiently effective even as a single agent. Materials and Methods: Patients with hematologic malignancies treated with ABK who met the following criteria were included: 1) fever during neutropenia or functional neutropenia, 2) FN complicated by pneumonia, and 3) possible infection by antimicrobial-resistant Grampositive cocci. Results: This study encompassed 22 episodes involving 19 patients, of which, 15 (68.2%) were successfully treated with ABK. Of the nine episodes showing inadequate response to other anti-MRSA drugs, eight were successfully treated with ABK. Grade 2 or worse adverse events included acute kidney injury (13.6%) and increased transaminase levels (9.1%). Conclusion The present study demonstrated that ABK is effective and safe in patients with FN and concurrent pneumonia caused by antimicrobial-resistant Gram-positive cocci. ABK may also be effective in patients who are unresponsive to other anti-MRSA drugs. Therefore, ABK may be beneficial in the treatment of pneumonia caused by antimicrobial-resistant Gram-positive cocci in patients with FN.

Objective: To identify factors affecting adherence to medication, a subjective questionnaire survey was administered to schizophrenia patients regarding the prescribed antipsychotic formulations. Methods: We evaluated the patients’ satisfaction and dissatisfaction with prescribed antipsychotic formulations, and patients answered the Drug Attitude Inventory-10 Questionnaire (DAI-10). Inclusion criteria for patients are as follows:age between 20 and 75 years and taking antipsychotic agents containing the same ingredients and formulations, for at least 1 month. Results: In total, 301 patients answered the questionnaire survey. Tablets were found to be the most commonly used antipsychotic formulations among schizophrenia patients (n = 174, 57.8%), followed by long-acting injections (LAIs, n = 93, 30.9%). No significant differences in the formulation satisfaction level and DAI-10 scores were observed between all formulations. Formulations, except for LAI, were selected by physicians in more than half of the patients.Patients who answered “Decided by consultation with physicians” had significantly higher satisfaction levels and DAI-10 scores compared to those who answered “Decided by physicians” (4.11 ± 0.77 vs. 3.80 ± 1.00, p = 0.0073 and 6.20 ± 3.51 vs. 4.39 ± 4.56, p ＜ 0.001, respectively). Satisfaction levels moderately correlated with DAI-10 scores (r = 0.48, p ＜ 0.001). Conclusion No formulation had a high satisfaction level in all patients, and it is important to be reflect the patients’ individual preferences in pharmacotherapy. Shared decision-making in the selection of the formulations is seen to be useful for improving medication adherence.

Objective: The addition of maintenance olaparib to bevacizumab demonstrated a significant progression-free survival (PFS) benefit in patients with newly diagnosed, advanced ovarian cancer in the PAOLA-1/ENGOT-ov25 trial (NCT02477644). We evaluated maintenance olaparib plus bevacizumab in the Japan subset of PAOLA-1. Methods: PAOLA-1 was a randomized, double-blind, phase III trial. Patients received maintenance olaparib tablets 300 mg twice daily or placebo twice daily for up to 24 months, plus bevacizumab 15 mg/kg every 3 weeks for up to 15 months in total. This prespecified subgroup analysis evaluated investigator-assessed PFS (primary endpoint). Results: Of 24 randomized Japanese patients, 15 were assigned to olaparib and 9 to placebo. After a median follow-up for PFS of 27.7 months for olaparib plus bevacizumab and 24.0 months for placebo plus bevacizumab, median PFS was 27.4 versus 19.4 months, respectively (hazard ratio [HR]=0.34; 95% confidence interval [CI]=0.11–1.00). In patients with tumors positive for homologous recombination deficiency, the HR for PFS was 0.57 (95% CI=0.16–2.09). Adverse events in the Japan subset were generally consistent with those of the PAOLA-1 overall population and with the established safety and tolerability profiles of olaparib and bevacizumab. Conclusion: Results in the Japan subset of PAOLA-1 support the overall conclusion of the PAOLA-1 trial demonstrating that the addition of maintenance olaparib to bevacizumab provides a PFS benefit in patients with newly diagnosed, advanced ovarian cancer.