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A case of cystitis occurring after administration of nivolumab, an anti-programmed death-1 antibody, which was considered to be an immune-related adverse event, is reported. A 62-year-old man with pulmonary squamous cell carcinoma (T4N0M1a Stage IV) was being treated with nivolumab as fourth-line chemotherapy. He was hospitalized for a fever and diarrhea after 3 courses. Fasting and antibiotic medication reduced the fever and alleviated the diarrhea. He then developed cystitis with no evidence of infection. Cystoscopy showed diffused redness and erosion of the bladder mucosa; urine cytology was negative. Imaging examinations showed no abnormalities. Urinary tract pain and hematuria due to nivolumab were diagnosed by exclusion following a bladder biopsy. Since symptomatic treatment was unsuccessful, steroid pulse therapy was given, which resolved the patient’s signs and symptoms. The patient was then switched to maintenance prednisolone and tapered gradually. The 4th course of nivolumab was then resumed with concomitant administration of steroid, and it was possible to continue administration of nivolumab without progression of cystitis.

A bstract Dyonic non-Abelian local/semi-global vortex strings are studied in detail in supersymmetric/non-supersymmetric Yang-Mills-Higgs theories. While the BPS tension formula is known to be the same as that for the BPS dyonic instanton, we find that the non-BPS tension formula is approximated very well by the well-known tension formula of the BPS dyon. We show that this mysterious tension formula for the dyonic non-BPS vortex stings can be understood from the perspective of a low energy effective field theory. Furthermore, we propose an efficient method to obtain an effective theory of a single vortex string, which includes not only lower derivative terms but also all order derivative corrections by making use of the tension formula. We also find a novel dyonic vortex string whose internal orientation vectors rotate in time and spiral along the string axis.

We conducted this study to determine whether substitution with anti-androgen (SOA) and tegafur-uracil (a pro-drug of 5-FU) combination therapy is more effective than SOA alone after relapse from initial hormonal therapy. Patients who were histologically confirmed and relapsed after initial hormonal therapy were included. All patients were randomly allocated into two groups: SOA alone (group A) or SOA combined with tegafur-uracil (group B). The mRNA expression of four enzymes, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT) and thymidine phosphorylase (TP), in prostate cancer cells was analyzed by quantitative reverse-transcription polymerase chain reaction. Fifty-two patients were enrolled in this study. The median age was 77 (range: 47-92) years. The PSA response rate in group B (61.5%) tended to be higher compared to that in group A (34.6%) (p=0.095). Group B (median: 15.9 months) had a significantly longer time to PSA progression (TTP) compared to group A (6.4 months) (p=0.014). In patients with a lower TS expression or a higher OPRT expression, group B demonstrated a higher PSA response rate compared to group A (p=0.019 and p=0.041, respectively). In addition, in the patients with a lower TS expression, group B demonstrated a significantly longer TTP compared to group A (p=0.018). There were no severe adverse events in either treatment group. After relapse from initial hormonal therapy, SOA combined with tegafur-uracil is effective and well tolerated. The TS mRNA expression level may be a predictive factor for this combination therapy.

Dyonic non-Abelian local/semi-global vortex strings are studied in detail in supersymmetric/non-supersymmetric Yang-Mills-Higgs theories. While the BPS tension formula is known to be the same as that for the BPS dyonic instanton, we find that the non-BPS tension formula is approximated very well by the well-known tension formula of the BPS dyon. We show that this mysterious tension formula for the dyonic non-BPS vortex stings can be understood from the perspective of a low energy effective field theory. Furthermore, we propose an efficient method to obtain an effective theory of a single vortex string, which includes not only lower derivative terms but also all order derivative corrections by making use of the tension formula. We also find a novel dyonic vortex string whose internal orientation vectors rotate in time and spiral along the string axis.

ABCG2, also known as BCRP, is a high-capacity urate exporter, the dysfunction of which raises gout/hyperuricemia risk. Generally, hyperuricemia has been classified into urate 'overproduction type' and/or 'underexcretion type' based solely on renal urate excretion, without considering an extra-renal pathway. Here we show that decreased extra-renal urate excretion caused by ABCG2 dysfunction is a common mechanism of hyperuricemia. Clinical parameters, including urinary urate excretion, are examined in 644 male outpatients with hyperuricemia. Paradoxically, ABCG2 export dysfunction significantly increases urinary urate excretion and risk ratio of urate overproduction. Abcg2 -knockout mice show increased serum uric acid levels and renal urate excretion, and decreased intestinal urate excretion. Together with high ABCG2 expression in extra-renal tissues, our data suggest that the 'overproduction type' in the current concept of hyperuricemia be renamed 'renal overload type', which consists of two subtypes—'extra-renal urate underexcretion' and genuine 'urate overproduction'—providing a new concept valuable for the treatment of hyperuricemia and gout. Hyperuricemia, or gout, is thought to arise either from urate overproduction or from decreased renal excretion of urate. Ichida et al . show that the extra-renal excretion of urate also has a role in the pathogenesis of hyperuricemia, and propose a new classification for patients with this disease.

ObjectiveThe aim of this study was to evaluate the efficacy and safety of high-dose taurine supplementation for prevention of stroke-like episodes of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), a rare genetic disorder caused by point mutations in the mitochondrial DNA that lead to a taurine modification defect at the first anticodon nucleotide of mitochondrial tRNALeu(UUR), resulting in failure to decode codons accurately.MethodsAfter the nationwide survey of MELAS, we conducted a multicentre, open-label, phase III trial in which 10 patients with recurrent stroke-like episodes received high-dose taurine (9 g or 12 g per day) for 52 weeks. The primary endpoint was the complete prevention of stroke-like episodes during the evaluation period. The taurine modification rate of mitochondrial tRNALeu(UUR) was measured before and after the trial.ResultsThe proportion of patients who reached the primary endpoint (100% responder rate) was 60% (95% CI 26.2% to 87.8%). The 50% responder rate, that is, the number of patients achieving a 50% or greater reduction in frequency of stroke-like episodes, was 80% (95% CI 44.4% to 97.5%). Taurine reduced the annual relapse rate of stroke-like episodes from 2.22 to 0.72 (P=0.001). Five patients showed a significant increase in the taurine modification of mitochondrial tRNALeu(UUR) from peripheral blood leukocytes (P<0.05). No severe adverse events were associated with taurine.ConclusionsThe current study demonstrates that oral taurine supplementation can effectively reduce the recurrence of stroke-like episodes and increase taurine modification in mitochondrial tRNALeu(UUR) in MELAS.Trial registration numberUMIN000011908.

BackgroundOptimal management of non-functioning pancreatic neuroendocrine tumors (PanNETs) ≤20 mm is controversial. The biological heterogeneity of these tumors poses challenges when deciding between resection and observation.MethodsIn this multicenter, retrospective cohort study, we analyzed all patients (n = 78) who underwent resection of non-functioning PanNETs ≤20 mm at three tertiary medical centers from 2004 to 2020 to assess the utility of preoperatively available radiological features and serological biomarkers of non-functioning PanNETs in choosing an optimal surgical indication. The radiological features included non-hyper-attenuation pattern on enhancement computed tomography (CT; hetero/hypo-attenuation) and main pancreatic duct (MPD) involvement, and serological biomarkers included elevation of serum elastase 1 and plasma chromogranin A (CgA) levels.ResultsOf all small non-functioning PanNETs, 5/78 (6%) had lymph node metastasis, 11/76 (14%) were WHO grade II, and 9/66 (14%) had microvascular invasion; 20/78 (26%) had at least one of these high-risk pathological factors. In the preoperative assessment, hetero/hypo-attenuation and MPD involvement were observed in 25/69 (36%) and 8/76 (11%), respectively. Elevated serum elastase 1 and plasma CgA levels were observed in 1/33 (3%) and 0/11 (0%) patients, respectively. On multivariate logistic regression analysis, hetero/hypo-attenuation (odds ratio [OR] 6.1, 95% confidence interval [CI] 1.7–22.2) and MPD involvement (OR 16.8, 95% CI 1.6–174.3) were significantly associated with the high-risk pathological factors. The combination of the two radiological worrisome features correctly predicted non-functioning PanNETs with high-risk pathological factors, with about 75% sensitivity, 79% specificity, and 78% accuracy.ConclusionsThis combination of radiological worrisome features can accurately predict non-functioning PanNETs that may require resection.

Improved cancer treatment outcomes have increased the demand for medical care that considers the quality of life of patients with cancer. Patient-reported outcomes (PROs) help assess the quality of life because they involve direct evaluation of the patients. Recently, electronic PROs (ePROs) have been used in clinical cancer care settings in Europe and the United States. Electronic PROs positively affected communication between patients with cancer and healthcare providers, enhanced education, optimized self-management, contributed to healthcare economics, assisted in monitoring adverse events, and improved prognosis. However, challenges such as adherence, burden on healthcare providers, lack of personalized formats, low digital literacy, and implementation costs remain. Therefore, carefully selecting the items to be recorded by ePROs in alignment with specific objectives is essential. Additionally, developing systems using lifelogs—digital records of daily activities—and creating mechanisms that automatically encourage patient behavioral changes based on the reported data are crucial. This review delineates the advantages and challenges of ePROs according to their history and proposes the prospects of ePRO.