Rapidly progressive cognitive impairment resulting in heavy psychosocial burden in a patient with Fabry disease undergoing hemodialysis: a case report.

BACKGROUND: Long-term enzyme replacement therapy (ERT) may improve prognosis in the patients with Fabry disease (FD), however, detail psychosocial burden has not been focused on long life expectancy. We experienced a male case of FD under ERT, he was placed on hemodialysis and presented rapidly progressive cognitive function. CASE PRESENTATION: A 51-year-old male patient with FD has been receiving ERT from age of 38 years. Hemodialysis was initiated at the age of 47 years. The patient experienced several attacks of cerebral infarction, and brain images demonstrated wide-spread asymptomatic ischemic lesions. His behavior became problematic at the age of 51 years. He often exhibited restlessness during hemodialysis sessions and failure to communicate effectively. The patient experienced impairment of attention and executive function, topographical disorientation, and amnesia. Consequently, it was necessary for medical staff and family members to monitor his behavior for safe extracorporeal circulation and daily life activities. Annual standardized neuropsychiatric testing revealed worsening of cognitive performance. CONCLUSIONS: Despite treating with long-term ERT, it is necessary to determine the psychosocial burden derived from the progression of cognitive impairment in patients with FD undergoing hemodialysis.

Epidemiology and Management of Drug-induced Liver Injury: Importance of the Updated RUCAM.

Drug-induced liver injury (DILI) is a major cause of acute liver injury, liver failure, and liver transplantation worldwide. In recent years, immune checkpoint inhibitors have become widely used. This has led to an increase in DILI, for which pathophysiology and management methods differ significantly from the past. As the number of cases of acute liver injury and liver transplantation due to DILI is expected to increase, information about a DILI is becoming more valuable. DILI is classified into two types according to its etiology: intrinsic DILI, in which the drug or its metabolites cause liver damage that is dose-dependent and predictable; and idiosyncratic DILI, in which liver damage is also dose-independent but unpredictable. In addition, depending on the course of the disease, chronic DILI or drug-induced autoimmune hepatitis may be present. The number of DILI cases caused by antimicrobial agents is decreasing, whereas that caused by drugs for malignant tumors and health foods is increasing. The Roussel Uclaf Causality Assessment Method is widely used to assess causality in DILI. Liver injury is a type of immune-related adverse event. The pattern of hepatic injury in immune-related adverse events is mostly hepatocellular, but mixed type and bile stasis have also been reported. Sclerosing cholangitis caused by immune checkpoint inhibitors has also been reported as a unique type of injury. Treatment mainly comprises withdrawal of immune checkpoint inhibitors and steroid administration; however, mycophenolate mofetil may be considered if the disease is refractory to steroids.

Real-world assessment of SmartExam, a novel FibroScan computational method: A retrospective single-center cohort study.

BACKGROUND AND AIM: SmartExam is a novel computational method compatible with FibroScan that uses a software called SmartDepth and continuous controlled attenuation parameter measurements to evaluate liver fibrosis and steatosis. This retrospective study compared the diagnostic accuracy of conventional and SmartExam-equipped FibroScan for liver stiffness measurement (LSM). METHODS: The liver stiffness and the associated controlled attenuation parameters of 167 patients were measured using conventional and SmartExam-Equipped FibroScan as well as reference methods like magnetic resonance elastography (MRE) and magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) measurements to assess its diagnostic performance. M or XL probes were selected based on the probe-to-liver capsule distance for all FibroScan examinations. RESULTS: The liver stiffness and controlled attenuation parameter (CAP) correlation coefficients calculated from conventional and SmartExam-equipped FibroScan were 0.97 and 0.82, respectively. Using MRE/MRI-PDFF as a reference and the DeLong test for analysis, LSM and the area under the receiver operating characteristic curve for CAP measured by conventional and SmartExam-equipped FibroScan showed no significant difference. However, the SmartExam-equipped FibroScan measurement (33.6 s) took 1.4 times longer than conventional FibroScan (23.2 s). CONCLUSIONS: SmartExam has a high diagnostic performance comparable with that of conventional FibroScan. Because the results of the conventional and SmartExam-equipped FibroScan were strongly correlated, it can be considered useful for assessing the fibrosis stage and steatosis grade of the liver in clinical practice, with less variability but little longer measurement time compared with the conventional FibroScan.

A 3-step approach to predict advanced fibrosis in nonalcoholic fatty liver disease: impact on diagnosis, patient burden, and medical costs.

A 2-step approach, Fibrosis-4 index (FIB-4) followed by vibration-controlled transient elastography (VCTE), has been proposed to predict advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to develop a novel 3-step approach for predicting advanced fibrosis. We enrolled 284 biopsy-confirmed NAFLD patients from two tertiary care centers and developed subgroups (n = 190), including 3.7% of patients with advanced fibrosis, assuming a primary care setting. In the 3-step approach, patients with intermediate-to-high FIB-4 in the first step underwent an enhanced liver fibrosis test or measurement of type IV collagen 7S domain as the second step, and VCTE was performed if the second step value was higher than the cutoff. In 284 cases, a tertiary care cohort with 36.3% advanced fibrosis, the 3-step approach showed significantly higher specificity and positive predictive value than the 2-step approach. In the subgroup with 3.7% advanced fibrosis, the 3-step approach significantly reduced the referral rate to specialists, the number of high-risk patients (i.e., liver biopsy candidates), and healthcare costs by 12.5% to 15.8%. The 3-step approach may improve the diagnostic performance to predict advanced fibrosis in NAFLD, which could lower rates of referrals to specialists, liver biopsies, and medical costs.

[Promotion of Diversity in the Academic Field of Urology : Analysis of 10,000 Articles Published in Acta Urologica Japonica during a 65-Year Period].

Gender equality is one of the most important issues in the promotion of diversity. The participation status of female urologists in academic activities has not been clarified. In the present study, we analyzed a total of 10,288 articles published by 58,914 authors in Acta Urologica Japonica since the first issue in 1955 to the present. The author's gender was determined by an application program interface for gender estimation in combination with independent manual confirmation by two researchers. The increasing rate (⊿person/⊿year) of female authors was as low as 0.067 in 1955-79, but increased to 0.400 in 1980-2000 and 0.814 in 2001-20. Over the time periods, the annual total numbers of female authors (person/year) showed an increasing trend from 3.2 in 1955-79 to 16.3 in 1980-2000 and 26.0 in 2001-20. The numbers of female author individuals, the ratio of female authors to all authors and the ratio of publications by female first author to all publications also showed similar trends. These results suggest that gender equality is becoming more prevalent in the academic field of urology. The methods and data of this study are considered to be useful for the promotion of gender equality in the academic field of urology for the future.

Efficacy of preoperative frailty assessment in patients with gastrointestinal disease.

AIM: The role of preoperative frailty assessment in patients with gastrointestinal (GI) disease remains unclear. This study aimed to clarify the relationship between frailty and postoperative outcomes in patients with GI disease. METHODS: This study investigated 42 patients (aged ≥65 years) with GI disease who underwent abdominal surgery. The frailty status was analyzed using the Japanese version of the Cardiovascular Health Study criteria. We also investigated postoperative outcomes. RESULTS: Of the 42 patients, seven (16.7%) were robust, 24 (57.1%) were prefrail and 11 (26.2%) were frail. Postoperative complications were observed in 45.5% and 63.6% of prefrail and frail patients, respectively, whereas no complications were found in robust patients (P = 0.026). The median hospital stay was 15, 19.5 and 27 days in robust, prefrail and frail patients, respectively (P < 0.01). CONCLUSION: Preoperative frailty status based on the Japanese version of the Cardiovascular Health Study criteria is associated with postoperative complication incidence and hospital stay extension in patients with GI disease. Geriatr Gerontol Int 2021; ••: ••-••.

Development of a portable reverse transcription loop-mediated isothermal amplification system to detect the E1 region of Chikungunya virus in a cost-effective manner.

Chikungunya fever is a mosquito-borne disease cause of persistent arthralgia. The current diagnosis of Chikungunya virus (CHIKV) relies on a conventional reverse transcription polymerase chain reaction assay. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a rapid and simple tool used for DNA-based diagnosis of a variety of infectious diseases. In this study, we established an RT-LAMP system to recognize CHIKV by targeting the envelope protein 1 (E1) gene that could also detect CHIKV at a concentration of 8 PFU without incorrectly detecting other mosquito-borne viruses. The system also amplified the E1 genome in the serum of CHIKV-infected mice with high sensitivity and specificity. Moreover, we established a dry RT-LAMP system that can be transported without a cold chain, which detected the virus genome in CHIKV-infected patient samples with high accuracy. Thus, the dry RT-LAMP system has great potential to be applied as a novel CHIKV screening kit in endemic areas.

[Anatomical Variation of the Origin of the Right Renal Artery : Assessment with an Angle of the Origin and Ventral Protrusion].

The right renal artery has been considered to originate laterally from the anterior aspect of aorta. In some cases, it turns more ventrally than the aorta, which can lead to intraoperative right renal artery injury. For this reason, we evaluated how the right renal artery turns ventrally and analyzed the factors for ventral protrusion of the right renal artery. We examined contrast-enhanced computed tomography images of 195 individuals and measured their angles of the right renal artery and ventral protrusion from the aorta. Age and sex had no significant correlation with these variations. A weaknegative correlation was found between body mass index and these variations. Almost all the right renal artery originated from the ventral side of the aorta, and almost half the right renal artery arose ventrally more than the aorta. Careful attention should be paid to ventral protrusion of the right renal artery to prevent vascular injury during surgery using the anterior approach to the upper retroperitoneum.

Assessment of 10-year changes in liver stiffness using vibration-controlled transient elastography in non-alcoholic fatty liver disease.

AIM: Although liver biopsy is the gold standard for the diagnosis and staging of non-alcoholic fatty liver disease (NAFLD), repeated assessment of patients' liver tissue conditions are impractical. We assessed the 10-year changes in liver stiffness measurements (LSM) utilizing vibration-controlled transient elastography in NAFLD patients. METHODS: From January 2006 to September 2007, LSM was carried out for 97 biopsy-proven NAFLD patients. Of these, 34 patients underwent 10-year LSM reassessments (14 of them with paired biopsies). RESULTS: We evaluated the changes in the fibrosis stage as estimated using LSM (FS-LSM). Over a 10-year period, 32.4% had FS-LSM progression, 50% had static disease, and 17.6% had FS-LSM improvement. From among the initially diagnosed non-alcoholic steatohepatitis patients, 18% had progressed to considerable stage 4 (cirrhosis) 10 years later. In this cohort, none of the patients who had been initially diagnosed as FS-LSM stage 0 had progressed to cirrhosis 10 years later. The changes in LSM were correlated with the change in the histological fibrosis stage, the NAFLD activity score, and the change in the sum of the steatosis, activity, and fibrosis score. Improving more than 1 body mass index (kg/m2 ) and having a higher initial aspartate aminotransferase, alanine aminotransferase (ALT), or ALT responder (>30% improvement or reduction to less than 40 IU/L) were factors contributing to LSM improvements (≥2 kPa). CONCLUSIONS: Vibration-controlled transient elastography is likely to become a more clinically important tool for the long-term monitoring of NAFLD patients.

Comparison of Number Versus Ratio of Positive Lymph Nodes in the Assessment of Lymph Node Status in Extrahepatic Cholangiocarcinoma.

BACKGROUND: This study aimed to compare the utility of the number of positive lymph nodes with the lymph node ratio (LNR) in predicting survival after resection of extrahepatic cholangiocarcinoma. METHODS: A retrospective analysis of 142 consecutive patients who underwent radical resection of extrahepatic cholangiocarcinoma was performed. A total of 3066 regional lymph nodes were resected. The median number of nodes per patient was 21. The optimal cutoff values for the number of positive nodes and the LNR were determined using the Chi square scores calculated by the Cox proportional hazards regression model. RESULTS: Nodal disease was found in 59 patients (42 %). In the subsequent analysis of the impact that nodal status has on survival, 18 patients with R1/2 resection and 6 patients with paraaortic nodal disease who did not survive for more than 5 years after resection were excluded. The optimal cutoff value for the number of positive nodes was 1, and the optimal cutoff value for the LNR was 5 %. Univariate analysis identified both the number of positive nodes (0, 1, or ≥2; P = 0.005) and the LNR (0, 0-5, or >5 %; P = 0.007) as significant prognostic factors. Multivariate analysis identified the number of positive nodes but not the LNR as an independent prognostic factor (P = 0.012). The 5-year survival rates were 64 % for the patients with no positive nodes, 46 % for the patients with one positive node, and 28 % for the patients with two or more positive nodes. CONCLUSIONS: The number of positive lymph nodes predicts survival better than the LNR after resection of extrahepatic cholangiocarcinoma, provided that nodal evaluation is sufficient.

[Socioeconomic advantages of longer screening intervals for men with low prostate-specific antigen levels in prostate cancer mass screening].

In prostate specific antigen (PSA) -based prostate cancer mass screening, the optimal re-screening interval is still in question, although guidelines suggest that a prolonged interval would be safe and cost-saving. We examined the socioeconomic feasibility of prolonged re-screening interval based on individual baseline PSA values. Markov decision-analytic models of prostate cancer screening were established for cost-effectiveness comparison of prolonged re-screening in men with low (≦1 ng/ml) PSA level (meta-interval strategy) and annual re-screening in every participant (control strategy). Effectiveness and socioeconomic feasibility were evaluated according to quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER ; Δcost per ΔQALY), respectively. As a result, outcomes including cancer detection rates and stage shift suggested that these models well recapitulated actual prostate cancer mass screening. The meta-interval strategy was more cost-effective than the control strategy. The ICER for the control strategy with respect to the meta-interval strategy exceeded US$62, 000/QALY through the sensitivity analyses for every assumption. The meta-interval strategy was more effective and less expensive if the trade-off of impaired clinical outcomes caused by delayed detection was small. In conclusion, our models suggest that the meta-interval strategy is more cost-effective than annual screening. It can be even more effective if the interval is determined appropriately such that cancer can be detected within the therapeutic window.

[Evaluation of utility index of quality of life (QOL) in prostate cancer patients: comparison of QOL utility index EuroQol-5D (EQ-5D) and visual analogue scale (VAS) with health-related QOL questionnaires SF-36 and EPIC].

PURPOSE: For the management of patients with localized prostate cancer, a number of therapeutic options are available. To compare the therapeutic modalities, it is important and necessary to evaluate economical aspects based on cost-effectiveness analysis. In addition, the survival time adjusted by quality of life (QOL), quality adjusted life year (QALY), is more reliable than the crude survival time. Thus, the usefulness of the commonly used QOL utility indexes, EuroQol-5D (EQ-5D) and visual analogue scale (VAS, 0-100 points), was investigated in prostate cancer patients. PATIENTS AND METHODS: A total of 81 patients with prostate cancer were included. The patients were asked to answer the four sets of questionnaires (EQ-5D, VAS, SF-36 and EPIC). The QOL utility indexes (EQ-5D and VAS) were evaluated in relation to the general and prostate cancer-specific QOL questionnaires (SF-36 and EPIC, respectively). RESULTS: The results of EQ-5D and VAS were significantly correlated to all domains of the general QOL questionnaire (SF-36). On the contrary, no remarkable relationship of EQ-5D and VAS was observed with any domain (urinary, bowel, sexual or hormonal) of the prostate cancer-specific QOL questionnaire (EPIC). There was significant and close correlation between the actual values of VAS and the estimates of VAS calculated from SF-36 data (R = 0.53, p < 0.0001). CONCLUSIONS: The QOL utility indexes (EQ-5D and VAS) are pertinent to evaluation of QOL utility index in prostate cancer patients and can be utilized for cost-utility analysis. It is suggested that the accumulated data of SF-36 could be used by conversion to QOL utility index.

Inflammation-based prognostic score, prior to neoadjuvant chemoradiotherapy, predicts postoperative outcome in patients with esophageal squamous cell carcinoma.

BACKGROUND: Recent studies have revealed that Glasgow prognostic score (GPS), an inflammation-based prognostic score, is associated with poor outcome in a variety of tumors. However, few studies have investigated whether GPS measured prior to neoadjuvant chemoradiotherapy (nCRT) is useful for postoperative prognosis of patients with advanced esophageal squamous cell carcinoma (ESCC). METHODS: GPS was calculated on the basis of admission data as follows: patients with both an elevated C-reactive protein (>10 mg/L) and hypoalbuminaemia (<35 g/L) were allocated a GPS score of 2. Patients in whom only 1 of these biochemical abnormalities was present were allocated a GPS score of 1, and patients with a normal C-reactive protein and albumin were allocated a score of 0. All patients underwent radical en-bloc resection 3-4 weeks after nCRT. RESULTS: A total of 48 patients with clinical TNM stage II/III were enrolled. Univariate analyses revealed that there were significant differences in cancer-specific survival in relation to grade of response to nCRT (P = .004), lymph node status (P = .0065), lymphatic invasion (P = .0002), venous invasion (P = .0001), pathological TNM classification (P = .015), and GPS (P < .0001). GPS classification showed a close relationship with lymphatic invasion, venous invasion, and number of lymph node (P = .0292, .0473, and .0485, respectively). GPS was found to be the only independent predictor of cancer-specific survival (odds ratio, 0.17; 95% confidence interval, 0.06-0.52; P = .0019). CONCLUSIONS: GPS, measured prior to nCRT, is an independent novel predictor of postoperative outcome in patients with advanced ESCC.

Impact of improvement in specificity of primary screening test on total cost of prostate cancer mass screening.

OBJECTIVES: Improvement in the specificity of primary screening tests, without significant cost elevation of the assay, provides cost savings in prostate cancer screening programs by reducing unnecessary secondary screening procedures. The purpose of this study was to evaluate the economic impact of improvement in the specificity of primary screening tests and to estimate the socially acceptable cost elevation for improved specificity. METHODS: A decision-analytic model was designed to evaluate the total costs of prostate cancer mass screening according to the changes in the specificity and the cost of the primary screening test. All assumed factors were tested by three-way sensitivity analyses incorporating cost and specificity. RESULTS: The base case analysis showed that a 1% improvement in the specificity of the primary screening test provides a $1.19 cost reduction per participant. Sensitivity analyses showed that an acceptable cost elevation for a 1% improvement in the specificity ranged from 0.68 to 2.90 $/% with respect to changes in several factors in the screening program. CONCLUSIONS: The specificity and cost of the primary screening test has a significant economical impact on prostate cancer mass screening. For each screening program, it should be taken into consideration whether the cost of the new test deserves the specificity.

Tc-99m MAA SPECT in pectus excavatum: assessment of perfusion volume changes after correction by the Nuss procedure.

PURPOSE: The Nuss procedure is a minimally invasive technique for the repair of pectus excavatum. This investigation attempted to assess the impact of this corrective protocol on pulmonary functional volume through analysis of distribution volume data derived from Tc-99m MAA SPECT. MATERIAL AND METHODS: SPECT was performed in 3 patients before and 6 months after completion of the Nuss procedure. Before the clinical application of SPECT, phantom experiments were conducted to establish the threshold level based on the volume calculation program. Haller's index, a quantitative index of chest-wall deformity, was also obtained by x-ray CT. RESULTS: A threshold level of 30% was the most accurate determinant of pulmonary volume. Preoperative and postoperative Tc-99m MAA distribution volumes (MAA volume in mL) were 2812 and 3107 (an increase of 10%), 2212 and 2410 (9%), and 2341 and 2872 (23%), respectively. In all patients, MAA volume increased after corrective intervention. Changes were most striking in the left lung, which is affected to a greater extent by dislocation of the heart. Morphologic improvement in the lungs was also demonstrated by Haller's CT index in all patients, which decreased from 4.35, 3.52, and 10.67, preoperatively, to 3.45, 2.75, and 4.25, respectively, postoperatively. CONCLUSION: MAA volume assessment is an easy, suitable approach for detection of favorable changes produced by the Nuss procedure in pectus excavatum.

Assessment of body image alteration after renal surgery using a novel three-dimensional laser scanner.

OBJECTIVES: To evaluate the utility of a newly developed three-dimensional (3D) body surface laser scanner and evaluate the body surface image of patients undergoing renal surgery to determine the impact of surgery on body image alterations. METHODS: The body surface image in the upright position was obtained using the Bodyline Scanner (Hamamatsu Photonics K.K., Hamamatsu, Japan), a 3D body surface laser scanner, in 27 patients who had undergone renal surgery. We compared the objective results of body image scanning with the subjective results of a self-administered questionnaire on perception and concern about body image alteration. RESULTS: The abdominal body surface area and volume of the operative side was significantly larger than that of the contralateral side in 18 patients undergoing renal surgery using a flank incision (median area 50.7%, P = 0.002; volume 51.2%, P <0.001). A statistically significant difference was not observed in 9 patients undergoing transperitoneal or laparoscopic surgery (median area 50.0%, P = 0.34; volume 49.9%, P = 0.40). The volume alteration measured by the 3D body surface laser scanner correlated with the patients' perception (P = 0.01) and concern (P = 0.03) about postoperative body image alteration as assessed by the self-administered questionnaire. CONCLUSIONS: The 3D body surface scanner is promising as a tool in the medical field in that it enables a computerized body image to be constructed in the upright position that reflects patients' subjective perceptions well. Using this, we observed that the flank incision causes postoperative changes in body image perceptible to the patient and a cause for concern.