Lower pretreatment serum testosterone level predicts poor prognosis in the patients with metastatic hormone-sensitive prostate cancer undergoing androgen deprivation therapy.

OBJECTIVE: This study aimed to reveal the association between pretreatment serum testosterone levels and prognosis in patients with metastatic hormone-sensitive prostate cancer treated with androgen deprivation therapy. METHODS: A total of 91 patients were included in this retrospective study. Clinical data were obtained through chart review. Multivariate cox proportional hazards analyses addressed the impact of variables on castration-resistant prostate cancer-free and overall survivals. RESULTS: During a median follow-up of 41.7 months, 61 (67%) and 49 (54%) patients developed castration-resistant prostate cancer and died, respectively. The median castration-resistant prostate cancer-free and overall survivals were 15.5 and 59.9 months, respectively. The cutoff value for discriminating between low- and high-testosterone levels was determined as 450 ng/dl by calculating the receiver operating characteristic curve. Patients in the low-testosterone group (n = 37) had a significantly higher body mass index, worse comorbidities represented by the higher Charlson comorbidity index and higher serum lactate dehydrogenase levels, than those in the high-testosterone group (n = 54). Castration-resistant prostate cancer free and overall survivals were significantly shorter in the low-testosterone group than in the high-testosterone group (P = 0.021 and P < 0.001, respectively). Multivariate analysis identified testosterone level of <450 ng/dl as an independent factor predicting development of castration-resistant prostate cancer (hazard ratio 2.28, P = 0.007), along with high-volume disease and Gleason score 9-10. Similarly, testosterone level of <450 ng/dl was independently associated with shorter overall survival (hazard ratio 2.84, P = 0.006), along with higher Charlson comorbidity index, visceral metastasis and higher alkaline phosphatase level. CONCLUSIONS: Lower baseline serum testosterone levels predict poor prognosis in patients with metastatic hormone-sensitive prostate cancer.

Feasibility of assessing male osteoporosis using MRI IDEAL-IQ sequence of proximal femur in prostate cancer patients.

Osteoporosis is often accompanied by bone loss with fat accumulation of the red marrow. A novel technique for quantification of iron and fat content by MRI IDEAL-IQ can visualize hematopoietic areas and fatty deposits in bone marrow; however, the relationship between these indices and total hip bone mineral density (BMD) remains unclear. In this study, the proximal femur of 104 men who underwent pelvic MRI and bone densitometry prior to treatment for non-metastatic prostate cancer was retrospectively examined to investigate the R2* value to quantify iron and proton density fat fraction (PDFF) to assess bone marrow fat content. R2* was significantly positively correlated with BMD (r = 0.6017, p < 0.0001), and PDFF was not correlated with BMD (r = -0.1302, p = 0.0512). Patients with BMD T-score ≤ -2.5 had significantly lower R2* than patients with BMD T-score > -2.5; however, there was no significant difference in PDFF. In the ROC analysis, which examined the predictive ability of R2* with BMD T-score ≤ -2.5 as an outcome, the cut-off value of R2* was 50.7 s-1 (AUC 0.817). These results show R2* correlated with BMD. R2* may be a non-invasive surrogate marker for diagnosing male osteoporosis.

Incidence of genitourinary injuries in pelvic fractures: A 12-year single-center retrospective study.

OBJECTIVE: This study aimed to determine the epidemiology of genitourinary injuries in pelvic fractures and elucidate the clinical outcomes of patients with pelvic fractures with and without genitourinary injuries at a tertiary trauma center in Japan. METHODS: Patients with pelvic fractures in our tertiary trauma center between May 2009 and April 2021 were retrospectively assessed. The patients' demographics, mechanism of injury, and hospital course details were collected. The outcomes of patients with pelvic fractures with and without genitourinary injuries were compared. RESULTS: Of 402 patients with pelvic fractures, 18 (4.5%) had genitourinary injuries. Falls were the most common mechanisms of injury for all pelvic fractures The incidence of bladder, kidney, urethral, and testis injuries were 2.0%, 1.2%, 1.2%, and 0.5%, respectively. Patients with genitourinary injuries were significantly younger (median age, 26 vs. 51 years; p < 0.001), had a higher rate of intensive care unit admission (94% vs. 58%; p = 0.002), remained hospitalized longer (median duration, 82 vs. 45 days; p < 0.001), and had a longer intensive care unit stay (median duration, 6 vs. 2 days; p < 0.001) when compared to patients without genitourinary injuries. Genitourinary injuries were not associated with in-hospital mortality. CONCLUSIONS: The incidence of genitourinary injuries with pelvic fractures was 4.5%. The presence of genitourinary injuries was associated with a higher rate of intensive care unit admission, longer hospital stay, and longer intensive care unit stay, but it was not associated with in-hospital mortality.

Myelodysplastic syndrome occurring after enfortumab vedotin treatment for metastatic urothelial carcinoma.

Introduction: Enfortumab vedotin is an antibody-drug conjugate targeting Nectin-4 for the treatment of advanced urothelial carcinoma in patients previously treated with platinum-containing chemotherapy and immune checkpoint inhibitors. Common adverse events include rashes, peripheral neuropathy, and hyperglycemia. However, there are no reports on the development of myelodysplastic syndrome during enfortumab vedotin therapy in clinical settings. Case presentation: A 72-year-old male patient experienced prolonged and severe thrombocytopenia 18 weeks after the start of enfortumab vedotin therapy for metastatic urothelial carcinoma, requiring daily platelet transfusions. Bone marrow examination and chromosomal analysis confirmed the diagnosis of myelodysplastic syndrome. Treatment with eltrombopag proved to be effective. Conclusion: This is the first report of the development of myelodysplastic syndrome during enfortumab vedotin therapy in a clinical setting. Although rare, myelodysplastic syndrome can occur during enfortumab vedotin therapy.

Relationship between Femoral Proximal Bone Quality Assessment by MRI IDEAL-IQ Sequence and Body Mass Index in Elderly Men.

BACKGROUND: Bone assessment using the MRI DEAL-IQ sequence may have the potential to serve as a substitute for evaluating bone strength by quantifying the bone marrow hematopoietic region (R2*) and marrow adiposity (proton density fat fraction: PDFF). Higher body mass index (BMI) is associated with increased bone mineral density (BMD) in the proximal femur; however, the relationship between BMI and R2* or PDFF remains unclear. Herein, we investigated the correlation between BMI and MRI IDEAL-IQ based R2* or PDFF of the proximal femur. METHODS: A retrospective single-cohort study was conducted on 217 patients diagnosed with non-metastatic prostate cancer between September 2019 and December 2022 who underwent MRI. The correlation between BMI and R2* or PDFF of the proximal femur was analyzed using Spearman's rank correlation test. RESULTS: Among 217 patients (median age, 74 years; median BMI, 23.8 kg/m2), there was a significant positive correlation between BMI and R2* at the right and left proximal femur (r = 0.2686, p < 0.0001; r = 0.2755, p < 0.0001, respectively). Furthermore, BMI and PDFF showed a significant negative correlation (r = -0.239, p = 0.0004; r = -0.2212, p = 0.001, respectively). CONCLUSION: In elderly men, the increased loading on the proximal femur due to elevated BMI was observed to promote a decrease in bone marrow adiposity in the proximal femur, causing a tendency for a transition from fatty marrow to red marrow with hematopoietic activity. These results indicate that the MRI IDEAL-IQ sequence may be valuable for assessing bone quality deterioration in the proximal femur.

Comparison of oncological outcomes of upfront androgen receptor signaling inhibitors and combined androgen blockade in Japanese patients with metastatic castration-sensitive prostate cancer.

In recent years, randomized controlled trials have demonstrated that upfront androgen receptor signaling inhibitors (ARSIs) prolong overall survival (OS) compared with androgen deprivation therapy (ADT) alone or combined androgen blockade (CAB) in patients with metastatic castration-sensitive prostate cancer (mCSPC). However, it remains unclear whether upfront ARSI is superior to CAB in Asian populations, among which the efficacy of ADT/CAB is considered relatively high. In this study, we compared the oncological outcomes of upfront ARSI and CAB in Japanese patients with mCSPC. Patients with mCSPC who underwent systemic therapy between May 2009 and October 2023 were enrolled retrospectively. Propensity score matching (PSM) was performed to compare the castration-resistant prostate cancer-free survival (CRPC-FS), cancer-specific survival (CSS), and OS between patients treated with upfront ARSI (ARSI group) and those treated with CAB (CAB group). In total, 30 and 142 patients were enrolled in the ARSI and CAB groups, respectively. After PSM (25 patients in each group), CRPC-FS was significantly longer in the ARSI group than in the CAB group (median: 36.7 vs. 12.3 months, hazard ratio: 0.44, 95% confidence interval: 0.20-0.97, p = 0.035). No significant differences were observed in CSS or OS between the two groups. In conclusion, when compared to CAB, upfront ARSI might have the potential to extend CRPC-FS among individuals in the Japanese population.

Obstructive urosepsis caused by ureterosciatic hernia: A case report.

Ureterosciatic hernia (USH) is a relatively rare cause of ureteral obstruction. We report a case of a patient with obstructive urosepsis caused by USH and treated by ureteral stenting. An 83-year-old woman came to our hospital with symptoms of left lumbar back pain and fever. Enhanced computed tomography showed left hydronephrosis and ureteral protrusion through the greater foramen sciaticum. The patient was diagnosed with USH and underwent transurethral ureteral stenting. Eight months later, the ureteral stent was removed. There has been no recurrence of USH 6 months after removal of the ureteral stent.

Retroperitoneal capillary arteriovenous malformation mimicking a malignant neoplasm.

Introduction: Retroperitoneal tumors account for 0.2% of all neoplasms. Among these tumors, retroperitoneal vascular malformations are particularly rare, with most previously reported cases being venous malformations. Case presentation: A 72-year-old woman was diagnosed with a retroperitoneal tumor on abdominal computed tomography. The 27-mm diameter tumor was located away from the right kidney and major vessels in the right perirenal adipose tissue. Contrast-enhanced computed tomography revealed a heterogeneously enhanced tumor with well-defined borders. Dynamic contrast-enhanced magnetic resonance imaging revealed rapid enhancement in the arterial phase and a progressive filling-in pattern in the delayed phase. Although vascular malformation was suspected, a definitive diagnosis could not be established. The retroperitoneal tumor was excised laparoscopically for therapeutic and diagnostic purposes, and the histopathological diagnosis confirmed it as a capillary arteriovenous malformation. Conclusion: Herein, we presented a rare case of retroperitoneal capillary arteriovenous malformation that was difficult to definitively diagnose preoperatively.

Predictive Factors of Lower Urinary Tract Injuries and Spontaneous Voiding Failure After Pelvic Fractures.

BACKGROUND/AIM: This study aimed to describe the voiding patterns of patients after surgical treatment of pelvic fractures and determine the predictive factors of lower urinary tract injuries (LUTIs) and spontaneous voiding failure among patients with surgically treated pelvic fractures at a tertiary trauma center in Japan. PATIENTS AND METHODS: We retrospectively assessed patients with surgically treated pelvic fractures in our tertiary trauma center during May 2009-April 2021. We excluded patients who died during hospitalization and who had indwelling catheter prior to the injury. Patients' LUTIs and spontaneous voiding failure at discharge were recorded. Multivariate analysis was performed to assess the predictive factors of LUTIs and spontaneous voiding failure at discharge. RESULTS: In total, 334 eligible patients were identified. Among them, 301 patients (90%) voided spontaneously with or without diapers at discharge. Thirty-three patients required some form of catheterization for bladder drainage. LUTIs were found to be associated with chronological age [odds ratio (OR)=0.96; 95% confidence interval (CI)=0.92-0.99; p=0.024] and pelvic ring fracture (OR=12.0; 95%CI=1.39-255.2; p=0.024). Spontaneous voiding failure was associated with intensive care unit admission (OR=7.17; 95%CI=1.49-34.4; p=0.004). CONCLUSION: Overall, 10% of patients with surgically treated pelvic fractures were not able to void spontaneously at discharge. Spontaneous voiding failure after pelvic fractures was related to injury severity.

Penetrating penile injury due to the splintering of the floorboards in the gymnasium.

INTRODUCTION: We present the case of a patient with penetrating penile injury caused by splintering floorboards in a gymnasium. CASE PRESENTATION: A 24-year-old man was brought to the emergency department of our hospital because of an unintentional penetrating penile injury sustained while playing volleyball at a gymnasium. He dove into the wooden floor to fly-receive the ball. When sliding with his abdomen on the floor, a wooden splinter from the floorboard stuck from the base of his penis to near the glans penis. The splinter was gently removed without bleeding under local anesthesia. CONCLUSIONS: Splintering floorboards in gymnasiums can cause serious trauma, including penile injuries. Health-care workers and users of public facilities, such as gymnasiums, should be aware of the accident risk associated with wooden floors.

LOX index, a novel predictive biochemical marker for coronary heart disease and stroke.

BACKGROUND: Lectin-like oxidized LDL receptor 1 (LOX-1) is implicated in atherothrombotic diseases. Activation of LOX-1 in humans can be evaluated by use of the LOX index, obtained by multiplying the circulating concentration of LOX-1 ligands containing apolipoprotein B (LAB) times that of the soluble form of LOX-1 (sLOX-1) [LOX index = LAB x sLOX-1]. This study aimed to establish the prognostic value of the LOX index for coronary heart disease (CHD) and stroke in a community-based cohort. METHODS: An 11-year cohort study of 2437 residents age 30-79 years was performed in an urban area located in Japan. Of these, we included in the analysis 1094 men and 1201 women without history of stroke and CHD. We measured LAB and sLOX-1 using ELISAs with recombinant LOX-1 and monoclonal anti-apolipoprotein B antibody and with 2 monoclonal antibodies against LOX-1, respectively. RESULTS: During the follow-up period, there were 68 incident cases of CHD and 91 cases of stroke (with 60 ischemic strokes). Compared with the bottom quartile, the hazard ratio (HR) of the top quartile of LOX index was 1.74 (95% CI 0.92-3.30) for stroke and 2.09 (1.00-4.35) for CHD after adjusting for sex, age, body mass index, drinking, smoking, hypertension, diabetes, non-HDL cholesterol, and use of lipid-lowering agents. Compared with the bottom quartile of LOX index, the fully adjusted HRs for ischemic stroke were consistently high from the second to the top quartile: 3.39 (95% CI 1.34-8.53), 3.15 (1.22-8.13) and 3.23 (1.24-8.37), respectively. CONCLUSIONS: Higher LOX index values were associated with an increased risk of CHD. Low LOX index values may be protective against ischemic stroke.

Alanine racemase of alfalfa seedlings (Medicago sativa L.): first evidence for the presence of an amino acid racemase in plants.

We demonstrated several kinds of D-amino acids in plant seedlings, and moreover alanine racemase (E.C.5.1.1.1) in alfalfa (Medicago sativa L.) seedlings. This is the first evidence for the presence of amino acid racemase in plant. The enzyme was effectively induced by the addition of L- or D-alanine, and we highly purified the enzyme to show enzymological properties. The enzyme exclusively catalyzed racemization of L- and D-alanine. The K(m) and V(max) values of enzyme for L-alanine were 29.6 x 10(-3) M and 1.02 mol/s/kg, and those for D-alanine are 12.0 x 10(-3) M and 0.44 mol/s/kg, respectively. The K(eq) value was estimated to be about 1 and indicated that the enzyme catalyzes a typical racemization of both enantiomers of alanine. The enzyme was inactivated by hydroxylamine, phenylhydrazine and some other pyridoxal 5'-phosphate enzyme inhibitors. Accordingly, the enzyme required pyridoxal 5'-phosphate as a coenzyme, and enzymologically resembled bacterial alanine racemases studied so far.

An alternative protein standard to measure activity of LOX-1 ligand containing apoB (LAB) - utilization of anti-LOX-1 single- chain antibody fused to apoB fragment.

AIM: We have recently demonstrated that the circulating level of LOX-1 ligand containing apoB (LAB) predicts the risk of cardiovascular events; however, as is the case in other assays measuring oxidized LDL (oxLDL), chemical unstability and inter-lot variance of standard oxLDL may limit the utility of measuring LAB. This study aimed to develop an alternative protein standard that is simultaneously recognized by LOX-1 and anti-apoB antibody instead of copper-oxidized LDL. METHODS AND RESULTS: cDNAs encoding the variable regions of anti-LOX-1 monoclonal antibody were cloned from hybridomas and reorganized to express anti-LOX-1 single-chain variable fragment (Fv). cDNAs of four regions of human apoB (B1 to B4), which were reported to be epitopes of many anti-apoB antibodies, were also cloned. After confirming the respective reactivity of Fv and apoB fragments to LOX-1 and anti-apoB antibodies, cDNAs of Fv and apoB fragments were connected to express Fv-ApoB chimeric proteins. These fusion proteins were found to be recognized by both LOX-1 and anti-apoB antibodies. Among them, the fusion proteins of Fv-B1 and Fv-B3 gave saturable binding curves against immobilized LOX-1 when detected by anti-apoB antibodies. The binding curves of different Fv-B1 preparations to LOX-1 were almost identical while those of oxLDL varied among the preparations, suggesting better quality control of Fv-B1 preparations. CONCLUSIONS: The fusion proteins composed of Fv-form anti-LOX-1 antibody and apoB fragment are useful alternatives to copper-oxidized LDL in determining LAB, which would facilitate the application of modified LDL analyses to the clinical diagnosis and risk evaluation of cardiovascular disease.