Treatment selection in the clinical practice of systemic lupus erythematosus: results from the Kyushu Collagen Disease Network for Systemic Lupus Erythematosus (KCDN-SLE) registry.

OBJECTIVES: This study aimed to describe the treatment selection for systemic lupus erythematosus (SLE) using data from the Kyushu Collagen Disease Network for SLE (KCDN-SLE) registry, a multicenter prospective registry in Japan. METHODS: This study used data from patients registered between August 2022 and November 2023. Clinical characteristics, purpose of agent initiation, other candidate agents, and short-term efficacy and safety were evaluated. RESULTS: We analyzed 69 previously treated patients with SLE (mean age 43.7 years; 62 females, 7 males). Hydroxychloroquine, biological agents, and immunosuppressive agents were initiated during the maintenance phase in 12, 41, and 16 patients, respectively. In patients with active organ involvement, hydroxychloroquine and biological agents were widely used for initiation. In those who already achieved treatment goals, biological agents alone were predominantly selected. The SLE Disease Activity Index 2000 score and prednisolone dose declined significantly over a 6-month follow-up period. Among 48 patients with active disease, 22 achieved a lupus low disease activity state, but this had no evident association with the initiation of a biological agent. In total, 14 adverse events, predominantly infections, were observed. CONCLUSIONS: Biological agents were used preferentially, and the therapeutic agents were appropriately effective and mostly achieved the purpose of agent initiation.

Type 1 helper T cells generate CXCL9/10-producing T-bet+ effector B cells potentially involved in the pathogenesis of rheumatoid arthritis.

Efficacy of B-cell depletion therapy highlights the antibody-independent effector functions of B cells in rheumatoid arthritis (RA). Given type 1 helper T (Th1) cells abundant in synovial fluid (SF) of RA, we have determined whether Th1 cells could generate novel effector B cells. Microarray and qPCR analysis identified CXCL9/10 transcripts as highly expressed genes upon BCR/CD40/IFN-γ stimulation. Activated Th1 cells promoted the generation of CXCL9/10-producing T-bet+ B cells. Expression of CXCL9/10 was most pronounced in CXCR3+ switched memory B cells. Compared with peripheral blood, SFRA enriched highly activated Th1 cells that coexisted with abundant CXCL9/10-producing T-bet+ B cells. Intriguingly, anti-IFN-γ antibody and JAK inhibitors significantly abrogated the generation of CXCL9/10-producing T-bet+ B cells. B cell derived CXCL9/10 significantly facilitated the migration of CD4+ T cells. These findings suggest that Th1 cells generate the novel CXCL9/10-producing T-bet+ effector B cells that could be an ideal pathogenic B cell target for RA therapy.

Efficacy and Tolerability of Ombitasvir/Paritaprevir/Ritonavir in HCV Genotype 1-infected Elderly Japanese Patients.

INTRODUCTION AND AIM: We assessed the characteristics of virological response to a combination treatment of ombitasvir, paritaprevir, and ritonavir in hepatitis C virus genotype 1-infected elderly Japanese patients. MATERIAL AND METHODS: This multicenter prospective study was conducted at six locations in Japan. Seventy patients with chronic hepatitis C virus genotype 1b infection were orally administered ombitasvir/paritaprevir/ritonavir once daily for 12 weeks. The primary endpoint was the proportion of elderly patients with sustained virological response (SVR) 12 weeks after the completion of treatment. Adverse events were also recorded to evaluate drug safety and tolerability during the trial period. SVR in elderly patients (age > 65; 94% [47 / 50]) was lower than that in younger patients (100% [20 / 20]). RESULTS: No significant differences in SVR 12 weeks after the completion of treatment were observed between the age groups (P = 0.153). Adverse events were observed in 16 patients (23.3%). Multivariate analysis confirmed that the change or discontinuation of concomitant drugs owing to drug interactions was independent of risk factors for adverse events associated with this drug combination (P = 0.015; odds ratio, 15.9; 95% confidence interval, 1.79 - 148). Ombitasvir/paritaprevir/ritonavir combination treatment was highly effective in elderly patients. CONCLUSION: Tolerability should be monitored in older patients for whom concomitant medications are discontinued or changed because of drug interactions.

Wisteria floribunda agglutinin-positive human Mac-2 binding protein in decompensated cirrhosis.

BACKGROUND AND AIM: An assay for Wisteria floribunda agglutinin-positive human Mac-2 binding protein (WFA+ -M2BP) has been reported as a useful non-invasive marker for the evaluation of the staging of fibrosis in several chronic liver diseases. However, available data on the effect of WFA+ -M2BP level in decompensated cirrhosis patients were limited. It is important that these investigations can validate the diagnostic utility of WFA+ -M2BP in the full range of patients with liver cirrhosis. METHODS: A multicenter study was conducted at five locations in Japan. A total of 207 patients with liver cirrhosis were enrolled in the present study. To determine whether or not the WFA+ -M2BP value was associated with a progression of fibrosis among cirrhosis, this study examined WFA+ -M2BP levels between patients with cirrhosis in the decompensated and compensated groups. RESULTS: The numbers and proportions of compensated and decompensated patients were 113 (54.6%) and 94 (45.4%), respectively. The average WFA+ -M2BP levels were 2.22 ± 1.61 in the compensated group and 6.91 ± 5.04 in the decompensated group. Significantly higher WFA+ -M2BP levels were observed in the decompensated group than those in the compensated group (P < 0.0001). The respective cut-off index values for decompensated cirrhosis were estimated using receiver-operating characteristic curves for WFA+ -M2BP levels. Using a cut-off index value of 3.37 for WFA+ -M2BP, predicting decompensated cirrhosis had a sensitivity of 77.8% and a specificity of 86.7%. CONCLUSIONS: WFA+ -M2BP values were higher in patients with decompensated liver cirrhosis.

[Case report : bleeding from ileal conduit in a patient with portal hypertension due to liver cirrhosis type C].

A 68-year-old man treated for type C liver cirrhosis was referred to our hospital for evaluation of a bladder tumor. The patient underwent transurethral resection of bladder tumor. The histopathological diagnosis was urothelial cancer (G2>G3, T2) and he underwent radical cystectomy with ileal conduit urinary diversion. Starting 3 months postoperatively, he experienced bleeding from the mucosa of the ileal conduit. Computed tomography showed vascular dilatation around the ileal conduit. This was considered to be attributable to portal hypertension resulting from liver cirrhosis. Conservative therapy failed to achieve hemostasis. The patient was not considered to have indications for a transjugular intrahepatic portosystemic shunt (TIPS). He died from bleeding 22 months after radical cystectomy.

[A case report: a patient with paralysis of the lower half of the body being diagnosed with prostate cancer and primary spinal malignant lymphoma].

The patient was an 81-year-old man who visited our hospital for paralysis of the lower half of the body. He was suspected as having a spinal tumor by computed tomography and magetic resonance imaging, and also as having prostate cancer based on a high prostate specific antingen level. A prostate needle biopsy, thoracic spinal fusion and posterior decompression were performed. The patient was diagnosed as having prostate cancer and primary spinal malignant lymphoma. Hormone therapy and chemotherapy were started for the prostate cancer and primary spinal malignant lymphoma, respectively. However, the patient died of a complication from chemotherapy.

[Four cases of double bypass surgery involving choledochojejunostomy and gastrojejunostomy for inoperable peripancreatic head cancer].

Peripancreatic head cancer often causes obstructive jaundice and duodenal obstruction, which reduces the quality of life and hinders the administration of anti-cancer drugs. Here, we report 4 cases of double bypass surgery( biliary and gastric) for the treatment of inoperable peripancreatic head cancer. The patients' ages ranged from 64 to 72 years. Two patients had pancreatic head cancer and 2 had ampullary cancer. No postoperative morbidity was observed and all 4 patients resumed oral intake within 5 days after surgery and began receiving chemotherapy within 1 month after surgery. There was immediate relief of biliary obstruction in all 3 patients with obstructive jaundice. None of the patients experienced recurrence of obstructive jaundice requiring biliary drainage. Two patients who died of cancer were able to consume food orally just before they died. Although bypass surgery is more invasive than endoscopic stenting, it may be safe and useful not only for palliation, but also for induction or continuation of chemotherapy.

Head Gesture Interface for Mouse Stick Users by AAGI.

We developed a gesture interface (AAGI) for individuals with motor dysfunction who cannot use standard interface switches. These users have cerebral palsy, quadriplegia, or traumatic brain injury and experience involuntary movement, spasticity, and so on. In this paper, we describe a disabled user who utilizes a mouth stick for laptop PC input in daily life. Our objective is to lower the burden on his body by using gestures. To this end, we developed a "home position" for the head that enables gestures to coexist with the mouse stick usage. The results of basic experiments with five healthy participants indicate that our system has reached the level where it can be applied to actual disabled persons. Finally, we applied the system to a user with cerebral palsy asked him to perform web browsing.

Successful treatment with belimumab for immune thrombocytopenia associated with systemic lupus erythematosus: A report of two cases.

Immune thrombocytopenia (ITP) is a common complication of systemic lupus erythematosus (SLE). Glucocorticoids (GCs) and hydroxychloroquine are first-line therapy for SLE-associated ITP (SLE-ITP). SLE-ITP in most of patients is less severe and well controlled with GCs, but some of the patients are GC resistant and require additional immunosuppressants including calcineurin inhibitors, azathioprine, and rituximab. We present two cases of SLE-ITP patients treated with belimumab who were resistant to GCs and achieved remission. For severe SLE-ITP, belimumab has emerged as a novel induction therapeutic option.

A Simple Simulation System for Quantifying Buttock Loads Caused by Daily Activities of Wheelchair Users.

The purpose of this study is to quantify the load generated on the buttocks during wheelchair operation in order to clarify the cause of pressure injuries on the buttocks of wheelchair users. In the case of repeated measurements, pressure injuries may occur by conducting experiments with people with actual disabilities. In this study, we proposed a method of dynamic simulation using a humanoid model in order to carry out buttock load safely due to exercise. In addition, the load on the buttocks is quantified by reproducing a simulated cushion that reproduces the actual physical properties on the simulator. When we conducted an evaluation experiment of the developed simulation to quantify the buttock load, we confirmed the validity of this simulator in the front-back direction. On the other hand, the correlation with the actual data is low in the left-right direction, and it is considered necessary to improve the humanoid model in order to improve the accuracy.

Hereditary angio-oedema with normal C1-INH, developing recurrent acute abdomen after taking low-dose oestrogen-progestin: A case report.

Hereditary angio-oedema (HAE) is a rare genetic disease characterised by repeated episodes of temporary organ swelling. Three types of HAE are known, of which HAE with normal C1 inactivator is difficult to be diagnosed due to its lack of laboratory abnormalities. Here, we describe a case of HAE with normal C1 inactivator and recurrent acute abdomen following low-dose oestrogen-progestin therapy. Notably, genetic analysis by Sanger sequencing led to the identification of a recurrent heterozygous missense mutation c.988A > G (p.K330E) in the plasminogen (PLG) gene of the patient. Prophylactic tranexamic acid and on-demand selective bradykinin B2 receptor blockers are used to treat her symptoms.

[The significance of chemoradiation therapy for TNM cStage II - III esophageal squamous cell carcinoma].

UNLABELLED: The value of chemoradiation therapy (CRT) followed by surgery is unknown in Japan. PATIENT AND METHOD: Thirty Patients with TNM cStage II - III squamous cell carcinoma (SCC) of the esophagus were divided into CRT (40 Gy) followed by surgery( arm A) and definitive CRT( 60 Gy()arm B). The correlations between several clinicopathological factors and survival time were examined. RESULTS: The effective rate (CR+PR) of CRT was 75% in arm A versus 88.9% in arm B (p= 0.32). There was no significant difference about the median survival time (arm A: 17. 4 months, arm B: 12. 6 months, p= 0.18). The two-year survival rate was 40 . 4% in arm A versus 41 . 6% in arm B (p=0.35). CONCLUSION: Our retrospective study showed no significant difference in prognosis between CRT followed by surgery and definitive CRT. Definitive CRT might be a choice of therapy for curative esophageal carcinoma.

[Preoperative chemoradiotherapy with S-1 for advanced low rectal cancer].

We reviewed the patients with neoadjuvant chemoradiotherapy (CRT) with S-1 to evaluate the feasibility and effectiveness for locally advanced lower rectal cancer. The CRT regimen consisted of pelvic irradiation (45 Gy in fractions of 1.8 Gy), five days a week. A treatment of oral S-1 (80 mg/m2 per day) on days 1-14 and 22-35 was given during radiotherapy. Patients underwent a curative resection with lateral lymph node resection at 6-8 weeks intervals after neoadjuvant CRT. The response rate on pathological study was 60% (all were grade 2), and no patients had lateral lymph node metastases. Grade 1 or 2 adverse effects occurred in all patients during CRT, but the CRT was achieved in all patients. We found two patients had surgical complications with wound infection and one patient with anastomotic leakage. All complications were improved by conservative treatment. The neoadjuvant CRT was feasible and effective treatment for all patients with locally advanced rectal cancer. We have started a phase II study of the neoadjuvant CRT.

An optimal design method for preventing air bubbles in high-temperature microfluidic devices.

DNA analysis with the polymerase chain reaction (PCR) has become a routine part of medical diagnostics, environmental inspections, food evaluations, and biological studies. Furthermore, the development of a microscale PCR chip is an essential component of studies aimed at integrating PCR into a micro total analysis system (mu-TAS). However, the occurrence of air bubbles in microchannels complicates this process. In this study, we investigated a new technique based on the fluid dynamics of laminar flow that utilizes a small amount of mineral oil at the beginning of sample injection to prevent air bubbles from occurring in microchannels. We also further optimized the pressure, the length of the pressurizing channel and the volume of oil, thus making our microfluidic device more useful for high-temperature PCR. Additionally, quantitative continuous-flow PCR was performed using the optimized PCR chip in order to detect genetically modified (GM) maize. DNA was extracted from GM maize, MON 810, and non-GM maize at several concentrations from 0% (w/v) to 100% (w/v). The DNA amplification signals were then analyzed on the PCR chip using a laser-based system. The signal from our microfluidic PCR chip was found to increase in direct proportion to the initial GM maize concentration.

Diffusion weighted imaging in the detection of upper urinary tract urothelial tumors.

PURPOSE: Diffusion-weighted (DW) magnetic resonance imaging (MRI) provides information about the biophysical properties of tissues such as cell organization and density. DW imaging (DWI) is becoming important in the assessment of malignant tumors. The purpose of our study was to evaluate the capability and reliability of DWI in the evaluation of upper urinary tract urothelial tumors. MATERIALS AND METHODS: DWI was performed in seventeen patients with upper urinary tract urothelial tumor, previously diagnosed by either CT or retrograde pyelography. An histological evaluation was performed after surgical resection. Each MRI was carried out using a 1.5T superconductive magnet MRI system. DWI images were obtained with b value of 1000 s/mm(2) under normal breathing. The apparent diffusion coefficient (ADC) values were measured. RESULTS: In nine patients with renal pelvis tumors and seven patients with ureteral tumors, the lesions were shown as high-signal intensity in the corresponding region on DWI. In one patient with carcinoma in situ (CIS) of the ureter, the lesion was not depicted with DWI. The mean ADC value of the tumor was 1.125 + or - 0.217 x 10(-3) mm(2)/s and was significantly lower than those of the renal parenchyma (1.984 + or - 0.238 x 10(-3) mm(2)/s, p < 0.01) and the urine (2.941 + or - 0.315 x 10(-3) mm(2)/s, p < 0.01). CONCLUSIONS: In our study, the renal pelvic and ureteral tumors except CIS were shown clearly with DWI. Although further studies are required, DWI may take the place of invasive retrograde urography for detecting tumors of the upper urinary tract.

[A case report of locally advanced rectal carcinoma effectively treated with preoperative chemoradiotherapy].

The patient was an 80-year-old woman who was diagnosed with locally advanced low rectal cancer. It was unresectable and we performed chemoradiotherapy combined with S-1 (S-1 80 mg/m2, RT 1.8 Gy × 25, total 45 Gy). An effective reduction of primary region resulted in curative resection (super low anterior resection, D3 lymph node dissection, covering ileostomy) with preserving the anal sphincter. Histopathologically, therapeutic efficacy was Grade 2. Preoperative chemoradiation has been a standard therapy in Western countries and would control local recurrence. This case indicated that CRT could improve a rate of curative resection in patients with locally advanced rectal carcinomas.

An extract (THC-002) of Ba-Wei-Die-Huang-Wan inhibits expression of tachykinins, and P2X3 and TRPV1 receptors, and inhibits ATP-induced detrusor overactivity in spontaneously hypertensive rats.

AIMS: To investigate possible mechanisms of action of THC-002 (HARNCARE), a galenical produced from the traditional Chinese herbal mixture Ba-Wei-Die-Huang-Wan, which has been reported to improve lower urinary tract symptoms (LUTS) in patients. METHODS: Forty-five female SHRs were randomly separated into three groups. Two groups were given 20 ml physiological saline solution (PSS) per kg-body weight orally daily for 1 week. An hour after the administration of PSS, one of the groups received 20 mg THC-002 per kg body weight, and the other a similar volume of THC-002-free saline. The third group received no treatments. The bladders were analyzed by real time RT-PCR (n = 6) and immunohistochemistry (n = 3) for the expression of tachykinins and P2X3 and TRPV1 receptors. Cystometric investigation (n = 6) was conducted after intravesical instillation of saline followed by 5 mg/ml ATP solution. RESULTS: Treatment with PSS caused and upregulation of tachykinins and P2X3 and TRPV1 receptors, which was prevented in the group treated with THC-002. In the normal (non-treated) and non-THC-002-treated SHRs, instillation of the ATP solution decreased voiding interval, micturition volume, and bladder capacity compared to the instillation of saline. However, in the THC-002-treated SHRs, ATP instillation had no effect. CONCLUSIONS: In SHRs, THC-002 reduced the bladder expression of tachykinins and P2X3 and TRPV1 receptors, and inhibited ATP-induced detrusor overactivity. These effects may explain part of its beneficial effects on LUTS.

Gosha-jinki-gan reduces transmitter proteins and sensory receptors associated with C fiber activation induced by acetic acid in rat urinary bladder.

AIM: We determined if Gosha-jinki-gan, a traditional Chinese herbal mixture, reduced the presence of the tachykinins neurokinin A, neurokinin B, and substance P, as well as the transient receptor potential vanilloid 1 (TRPV1) and P2X3 purine receptors that are functionally associated with C fibers in the urinary bladder. METHODS: Thirty-six female rats were fed with either a standard diet or one supplemented with 1.08% Gosha-jinki-gan. After 4 weeks, the urinary bladders were instilled with either saline or 0.1% acetic acid. After 30 min, the bladders were removed and expression of the tachykinins and the TRPV1 and P2X3 receptors was determined by immunohistochemistry and mRNA expression. RESULTS: In rats fed with the standard diet, the tachykinins and the TRPV1 and P2X3 receptors expressed nearby or within urothelium of the acetic acid-treated rats increased compared with the saline-instilled rats. In rats pretreated with Gosha-jinki-gan, the tachykinins and the TRPV1 and P2X3 receptors in the acetic acid-treated rats also increased compared with the saline-instilled rats. However, with the instillation of acetic acid, the tachykinins and the TRPV1 and P2X3 receptors of Gosha-jinki-gan pretreated rats decreased compared with standard diet fed rats. The mRNA expression levels of neurokinin A, substance P, and the TRPV1 receptor in acetic acid-treated Gosha-jinki-gan pretreated rats were lower than that in acetic acid-treated standard diet fed rats. Gosha-jinki-gan did not destroy nerve fibers within the bladders. CONCLUSIONS: Gosha-jinki-gan partially reduced the tachykinins and TRPV1 and P2X3 purine receptors without destroying the nerve fibers.

Diversity and similarity of microbial communities in petroleum crude oils produced in Asia.

To understand microbial communities in petroleum crude oils, we precipitated DNA using high concentrations of 2,2,4-trimethylpentane (isooctane) and purified. Samples of DNA from five crude oils, (Middle East, 3; China, 1; and Japan, 1) were characterized based upon their 16S rRNA gene sequences after PCR amplification and the construction of clone libraries. We detected 48 eubacterial species, one cyanobacterium, and one archaeon in total. The microbial constituents were diverse in the DNA samples. Most of the bacteria affiliated with the sequences of the three oils from the Middle East comprised similar mesophilic species. Acinetobacter, Propionibacterium, Sphingobium and a Bacillales were common. In contrast, the bacterial communities in Japanese and Chinese samples were unique. Thermophilic Petrotoga-like bacteria (11%) and several anaerobic-thermophilic Clostridia- and Synergistetes-like bacteria (20%) were detected in the Chinese sample. Different thermophiles (12%) and Clostridia (2%) were detected in the Japanese sample.