Predictive value of polygenic risk score for prostate cancer incidence and prognosis in the Han Chinese.

Although prostate cancer is a common occurrence among males, the relationship between existing risk prediction models remains unclear. The objective of this hospital-based retrospective study is to investigate the impact of polygenic risk scores (PRSs) on the incidence and prognosis of prostate cancer in the Han Chinese population. A total of 24,778 male participants including 903 patients with prostate cancer at Taichung Veterans General Hospital were enrolled in the study. PRS was calculated using 269 single nucleotide polymorphisms and their corresponding effect sizes from the polygenic score catalog. The association between PRS and the risk prostate cancer was evaluated using Cox proportional hazards regression model. Among the 24,778 participants, 903 were diagnosed with prostate cancer. The risk of prostate cancer was significantly higher in the highest quartile of PRS distribution compared to the lowest (hazard ratio = 4.770, 95% CI = 3.999-5.689, p < 0.0001), with statistical significance across all age groups. Patients in the highest quartile were diagnosed with prostate cancer at a younger age (66.8 ± 8.3 vs. 69.5 ± 8.8, p = 0.002). Subgroup analysis of patients with localized or stage 4 prostate cancer showed no significant differences in biochemical failure or overall survival. This hospital-based cohort study observed that a higher PRS was associated with increased susceptibility to prostate cancer and younger age of diagnosis. However, PRS was not found to be a significant predictor of disease stage and prognosis. These findings suggest that PRS could serve as a useful tool in prostate cancer risk assessment.

Performance of red blood cell indices for the detection of reticulocytosis in anemic and non-anemic dogs in Taiwan.

Reticulocyte counts (RETIC) are considered the gold standard in detecting an erythroid bone marrow response (BMR) in anemic and non-anemic dogs. Reticulocytosis without anemia (RWA) is a potential indicator of disease. The prevalence of anemia or RWA, as well as the effectiveness of red blood cell (RBC) indices in identifying a BMR, may vary based on geographical locations and breed differences. The purpose of the study was to determine the prevalence of regenerative and nonregenerative anemia, and RWA in pet dogs of Taiwan, and to assess the sensitivity and specificity of combined increased mean cell volume and decreased mean cell hemoglobin concentration (iMCV+dMCHC) to detect reticulocytosis in this population. The final population analysis consisted of 149,076 dogs. A cross sectional, retrospective analysis of complete blood count (CBC) samples from a field of automated hematology analyzers in Taiwan from December 1, 2018 through December 31, 2020 was performed. Among 149,076 dogs, 11.8% (n=17,600) had reticulocytosis (RETIC > 110K/µl) and 21.8% (n=32,474) had anemia (HCT < 37.3%). Of 32,474 anemic dogs, 17.8% (n=5,789) had reticulocytosis. Of 116,602 dogs without anemia, 10.1% (n=11,776) had reticulocytosis. Across all dogs, sensitivity/specificity of iMCV+dMCHC to detect BMR was 4.3% and 99.4%, respectively compared to RETIC. Among anemic dogs, sensitivity/specificity of iMCV+dMCHC to detect BMR was 9.8% and 99.2%, respectively. Among non-anemic dogs, sensitivity/specificity of iMCV+dMCHC to detect BMR was 1.6% and 99.5%, respectively. Therefore, most regenerative anemias and cases of RWA did not have a combined iMCV+dMCHC. To avoid overlooking potential illness, RETIC should be evaluated regardless of whether patients have anemia or not.

Polygenic risk score predicting susceptibility and outcome of benign prostatic hyperplasia in the Han Chinese.

BACKGROUND: Given the high prevalence of BPH among elderly men, pinpointing those at elevated risk can aid in early intervention and effective management. This study aimed to explore that polygenic risk score (PRS) is effective in predicting benign prostatic hyperplasia (BPH) incidence, prognosis and risk of operation in Han Chinese. METHODS: A retrospective cohort study included 12,474 male participants (6,237 with BPH and 6,237 non-BPH controls) from the Taiwan Precision Medicine Initiative (TPMI). Genotyping was performed using the Affymetrix Genome-Wide TWB 2.0 SNP Array. PRS was calculated using PGS001865, comprising 1,712 single nucleotide polymorphisms. Logistic regression models assessed the association between PRS and BPH incidence, adjusting for age and prostate-specific antigen (PSA) levels. The study also examined the relationship between PSA, prostate volume, and response to 5-α-reductase inhibitor (5ARI) treatment, as well as the association between PRS and the risk of TURP. RESULTS: Individuals in the highest PRS quartile (Q4) had a significantly higher risk of BPH compared to the lowest quartile (Q1) (OR = 1.51, 95% CI = 1.274-1.783, p < 0.0001), after adjusting for PSA level. The Q4 group exhibited larger prostate volumes and a smaller volume reduction after 5ARI treatment. The Q1 group had a lower cumulative TURP probability at 3, 5, and 10 years compared to the Q4 group. PRS Q4 was an independent risk factor for TURP. CONCLUSIONS: In this Han Chinese cohort, higher PRS was associated with an increased susceptibility to BPH, larger prostate volumes, poorer response to 5ARI treatment, and a higher risk of TURP. Larger prospective studies with longer follow-up are warranted to further validate these findings.

Machine-learning Algorithm-based Risk Prediction and Screening-detected Prostate Cancer in A Benign Prostate Hyperplasia Cohort.

BACKGROUND/AIM: Prostate cancer (PCa) is lethal. Our aim in this retrospective cohort study was to use machine learning-based methodology to predict PCa risk in patients with benign prostate hyperplasia (BPH), identify potential risk factors, and optimize predictive performance. PATIENTS AND METHODS: The dataset was extracted from a clinical information database of patients at a single institute from January 2000 to December 2020. Patients newly diagnosed with BPH and prescribed alpha blockers/5-alpha-reductase inhibitors were enrolled. Patients were excluded if they had a previous diagnosis of any cancer or were diagnosed with PCa within 1 month of enrolment. The study endpoint was PCa diagnosis. The study utilized the extreme gradient boosting (XGB), support vector machine (SVM) and K-nearest neighbors (KNN) machine-learning algorithms for analysis. RESULTS: The dataset used in this study included 5,122 medical records of patients with and without PCa, with 19 patient characteristics. The SVM and XGB models performed better than the KNN model in terms of accuracy and area under curve. Local interpretable model-agnostic explanation and Shapley additive explanations analysis showed that body mass index (BMI) and late prostate-specific antigen (PSA) were important features for the SVM model, while PSA velocity, late PSA, and BMI were important features for the XGB model. Use of 5-alpha-reductase inhibitor was associated with a higher incidence of PCa, with similar survival outcomes compared to non-users. CONCLUSION: Machine learning can enhance personalized PCa risk assessments for patients with BPH but more research is necessary to refine these models and address data biases. Clinicians should use them as supplementary tools alongside traditional screening methods.

Nephroscope-assisted single trocar peritoneal dialysis catheter insertion improves catheter survival compared with laparoscopic technique: Ten-year experience of a single-center.

BACKGROUND: An ideal technique for peritoneal dialysis (PD) catheter insertion should provide a long-term functioning catheter until permanent renal replacement therapy becomes available. We developed a technique using the nephroscope-assisted single-trocar approach in 2011. In this study, we report the outcomes, learning curve analysis and cost-effectiveness analysisof the nephroscopic approach compared with the traditional laparoscopic approach. METHOD: Between January 2005 and December 2020, we retrospectively reviewed 511 patients who received PD catheter insertions using the laparoscopic or nephroscopic approach. We compared the baseline characteristics of the patients, surgical outcomes, and complications of the two groups. We further analyzed the nephroscopic group to determine the cost-effectiveness analysis, learning curve and the complication frequency between the learning and mastery periods of the nephroscopic approach. RESULTS: A total of 208 patients underwent laparoscopic PD catheter insertion, whereas 303 patients received nephroscopic surgery. The median catheter survival in the nephroscopic group is significantly longer (43.1 vs. 60.5 months, p = 0.019). The incidence of peritonitis (29.3% vs.20.8%, p = 0.035) and exit site infection (12.5% vs. 6.6%, p = 0.019) were significantly lower in the nephroscopic group. The cost-effectiveness analysis showed a medical expense reduction of 16000 USD annually by using the nephroscopic technique. There was no difference in the frequency of surgical complications between the learning and mastery phases when examining the learning curve analysis for the nephroscopic technique. CONCLUSIONS: Compared with the traditional laparoscopic approach, the nephroscopic technique effectively prolonged catheter survival and reduces health care cost by reducing infectious complications. The low complication rate during the learning phase of surgery makes the procedure safe for patients and surgeons.

Safety, tolerability, and pharmacokinetics of TG-1000, a new molecular entity against influenza virus: first-in-human study.

Background: The cap-snatching mechanism of influenza virus mRNA transcription is strongly suppressed by TG-1000, a prodrug rapidly metabolized into TG-0527, is a potent cap-dependent nucleic acid endonuclease inhibitor. Herein, we aimed to assess the safety, tolerability, and pharmacokinetics of TG-1000 in healthy participants and the effect of food on the pharmacokinetics and safety of TG-1000. Method: The study was divided into 2 parts: Part A [Single Ascending-Dose (SAD) study, 10-160 mg] and Part B [Food-Effect (FE) study, 40 mg] were launched sequentially. The study included 66 participants for both investigations. We administered different TG-1000 capsules or placebo doses per the study protocol and collected blood samples for pharmacokinetic assessments at specific times. In plasma, TG-1000 and its active metabolite TG-0527 were assayed, and PK parameters were determined. Results: In SAD, the increase in AUC was less than the proportional increase in dose over the 20-160 mg dose range, while the increase in Cmax was proportional to the increase in dose. In the 10-160 mg dose range, T1/2, λz and Tmax of TG-0527 were dose-independent; and T1/2 and Tmax were within 33.8-39.4 h and 3.02-6 h, respectively. In FE, the AUC0-inf, AUC0-last, and Cmax of TG-0527 decreased by approximately 17.52%, 18.76%, and 41.35%, respectively, and the Tmax delay was around 1.50 h. No serious adverse events occurred during the studies. Conclusion: Overall, TG-1000 was well tolerated and exhibited an acceptable safety and PK profile, supporting further clinical investigation of TG-1000 for the treatment of influenza.

The impacts of MACC1 gene polymorphisms on urothelial cell carcinoma susceptibility and clinicopathologic characteristics in Taiwan.

Urothelial cell carcinoma (UCC) is a common malignancy of the urinary tract in Taiwan. Metastasis-Associated in Colon Cancer 1 (MACC1), a newly identified oncogene and regulator of the HGF/Met signaling pathway, has been shown to play a critical role in the development and progression of several types of cancer. Our study aims to investigate the impact of MACC1 gene polymorphisms on the clinicopathological features of patients with UCC. In this study, we included a total of 719 patients with UCC and 719 healthy controls. The genotyping of five MACC1 gene polymorphisms (rs1990172, rs975263, rs3095007, rs4721888, and rs3735615) was performed using real-time PCR with TaqMan assays. Our findings indicate that urothelial cancer patients with MACC1 rs3095007 A allele had a decreased risk of >T2 stage [Odds ratio (OR)=0.619, 95% CI=0.394-0.971, p=0.036] and lymph node invasion (OR=0.448, 95% CI=0.201-0.998, p=0.044). Additionally, these individuals were associated with longer relapse-free survival (p=0.007) and overall survival (p=0.028). In conclusion, our findings demonstrate that urothelial cancer patients with MACC1 (rs3095007) CA and AA genotypes have a lower risk of advanced T stage and lymph node metastasis. Additionally, these genotypes were associated with longer relapse-free survival and overall survival, highlighting the potential of these biomarkers as predictors of UCC prognosis.

Pharmacokinetics and Pharmacodynamics of Burixafor Hydrobromide (GPC-100), a Novel C-X-C Chemokine Receptor 4 Antagonist and Mobilizer of Hematopoietic Stem/Progenitor Cells, in Mice and Healthy Subjects.

Adequate mobilization of hematopoietic stem cells (HSCs), especially CD34+ cells, is necessary for stem cell transplantation in patients with hematological malignancies or autoimmune diseases. Burixafor is an inhibitor of the C-X-C Chemokine Receptor 4 that disrupts the C-X-C motif chemokine 12 (CXCL12)/CXCR4 axis in the bone marrow, releasing HSCs into circulation. In mice, a single intravenous dose of burixafor was rapidly absorbed (time to maximum concentration, 5 minutes) and increased peripheral white blood cell counts within 30 minutes. Additionally, burixafor was administered to 64 healthy subjects in a randomized, double-blind, placebo-controlled, single-ascending-dose study to evaluate safety, pharmacokinetics, and pharmacodynamics. Subjects received burixafor intravenous doses ranging from 0.10 to 4.40 mg/kg in 8 cohorts. Single doses were generally safe and well tolerated. Gastrointestinal events were reported at doses of 2.24 mg/kg or greater. Exposure (maximum concentration and area under the concentration-time curve) increased in an approximately dose-proportional manner. Time to maximum concentration occurred with a median of 0.26-0.30 hours that was not dose proportional. As expected, white blood cell, CD133+ cell, and CD34+ cell concentrations generally increased with the increases in burixafor dose from 0.10 to 3.14 mg/kg. At maximal levels, the CD34+ cell counts increased 3- to 14-fold from baseline levels. These results provide support for continued clinical development of burixafor.

Metastasectomy Improves Overall Survival in Metastatic Renal Cell Carcinoma: A Retrospective Cohort Study.

BACKGROUND/AIM: The use of complete metastasectomy for treating metastatic renal cell carcinoma (mRCC) has been shown to improve survival outcomes in the era of tyrosine kinase inhibitors (TKIs). However, its effectiveness in combination with immune checkpoint inhibitors (ICIs) remains unclear. Therefore, the objective of the study was to elucidate the impact of metastasectomy in patients with mRCC who received both TKIs or ICIs. PATIENTS AND METHODS: A total of 157 patients diagnosed with metastatic renal cell carcinoma (mRCC) between 2006 and 2018 in Taichung Veterans General Hospital were included in the study. Patients were divided into two groups: the non-metastasectomy group (n=89) and the metastasectomy group (n=68). Kaplan-Meier analyses and Cox proportional hazards models were employed to evaluate the impact of metastasectomy and other risk factors on overall survival (OS). RESULTS: Among patients who underwent metastasectomy, 62 patients (91.18%) underwent metastasectomy for more than 50% of their metastatic sites, and 42 patients (61.76%) received complete metastasectomy. The median overall survival was 55.75 months in the metastasectomy group, which was significantly longer than the 15.14 months observed in the non-metastasectomy group (p<0.001). Multivariate regression analysis revealed that metastasectomy had a significant impact on overall survival [hazard ratio (HR)=0.42, 95% confidence interval (CI)=0.26-0.67, p<0.001]. Additionally, performance status and lactate dehydrogenase were identified as independent predictors for overall survival. CONCLUSION: Combination of metastasectomy with systemic therapy was shown to improve overall survival in patients with mRCC. Therefore, this modality may be considered as a viable option for patients who are fit for surgical intervention and are undergoing treatment with either TKIs or ICIs.

Chronic kidney disease, preoperative use of antispasmodics and lower resected prostate volume ratios are risk factors for postoperative use of adrenergic Alpha-blockers and antispasmodics.

OBJECTIVES: Transurethral resection of prostate (TURP) and laser prostate surgery are common surgeries for benign prostate hyperplasia (BPH). We conducted an investigation using hospital database to evaluate the clinical factors associated with post-operative usage of alpha-blockers and antispasmodics. METHODS: This study was conducted using retrospective clinical data from the hospital database, which contained newly diagnosed BPH patients between January 2007 and December 2012 who subsequently received prostate surgery. The study end-point was the use of alpha-blockers or antispasmodics for at least 3 months duration after 1 month of surgery. The exclusion criteria was prostate cancer diagnosed before or after the surgery, recent transurethral surgeries, history of open prostatectomy, and history of spinal cord injury. Clinical parameters, including age, body mass index, preoperative prostate specific antigen value, comorbidities, preoperative usage of alpha-blockers, anstispasmodics and 5-alpha reductase inhibitors, surgical methods, resected prostate volume ratios, and preoperative urine flow test results, were evaluated. RESULTS: A total of 250 patients receiving prostate surgery in the database and confirmed pathologically benign were included. There was significant association between chronic kidney disease (CKD) and the usage of alpha-blockers after prostate surgery (OR = 1.93, 95% CI 1.04-3.56, p = 0.036). Postoperative antispasmodics usage was significantly associated with preoperative usage of antispasmodics (OR = 2.33, 95% CI 1.02-5.36, p = 0.046) and resected prostate volume ratio (OR = 0.12, 95% CI 0.02-0.63, p = 0.013). CONCLUSIONS: BPH patients with underlying CKD were more likely to require alpha-blockers after surgery. In the meantime, BPH patients who required antispasmodics before surgery and who received lower prostate volume resection ratio were more liable to antispasmodics after prostate surgery.

Geriatric nutritional risk index as a prognostic marker for patients with upper tract urothelial carcinoma receiving radical nephroureterectomy.

To investigate the prognostic value of the geriatric nutritional risk index (GNRI) in patients with upper tract urothelial cell carcinoma (UTUC) receiving radical nephroureterectomy (RNU). Between January 2001 and December 2015, we enrolled 488 patients with UTUC underwent RNU in Taichung Veterans General Hospital. GNRI before radical surgery was calculated based on serum albumin level and body mass index. The malnutritional status was defined as GNRI < 92.0. Using Kaplan-Meier analyses and Cox proportional hazards models to analyze the risk factors on disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). 386 patients were categorized as normal nutritional status (GNRI ≥ 92) and 102 patients as malnutritional status (GNRI < 92). We used the receiver operating characteristic (ROC) curve for determined the association between GNRI and OS, with area under the curve (AUC) being 0.69. The 5-year survival rate of DFS, CSS and OS were 48.6%, 80.5% and 80.5% in the normal nutritional group and 28.0%, 53.2% and 40% in the malnutritional group. Using the multivariate analysis, malnutritional status was found as an independent risk factor for OS (hazard ratio [HR] = 3.94, 95% confidence interval [CI] 2.70-5.74), together with age (HR = 1.04, 95% CI 1.02-1.06), surgical margin positive (HR = 1.78, 95% CI 1.13-2.82), pathological T3 (HR = 2.54, 95% CI 1.53-4.21), pathological T4 (HR = 6.75, 95% CI 3.17-14.37) and lymphovascular invasion (HR = 1.81, 95% CI 1.16-2.81). We also found GNRI index as independent risk factor in DFS (HR = 1.90, 95% CI 1.42-2.54) and CSS (HR = 5.42, 95% CI 3.24-9.06). Preoperative malnutritional status with low GNRI is an independent marker in predicting DFS, CSS and OS in UTUC patients underwent RNU.

Complete Cycles of Radium-223 Improve Overall Survival in Patients With Metastatic Castration-resistant Prostate Cancer: A Retrospective Study.

BACKGROUND/AIM: The aim of this study was to investigate whether complete cycles of Radium-223 (Ra-223) improved survival in patients with metastatic castration resistant prostate cancer (mCRPC). PATIENTS AND METHODS: We retrospectively analyzed mCRPC patients treated with Ra-223 at Taichung Veterans General hospital. Patient and disease characteristics, laboratory results, number of bone metastases, mCRPC treatment sequence, Ra-223 treatment cycles and survival outcomes were collected. Overall survival and progression-free survival (PFS) were analyzed with Kaplan-Meier analysis. Uni- and multivariate analysis was used to identify clinical-radiologic factors that influence outcomes. RESULTS: From October 2016 to December 2020, 42 patients with mCRPC were enrolled. Twenty-three patients received <4 cycles of Ra-223 for mCRPC and 19 patients received 5-6 cycles. The median PSA progression free survival was 2.07 months in the <4 cycles group, compared to 3.93 months in the 5-6 cycles group (log rank p=0.006). The median overall survival was 3.93 months in the <4 cycles group, compared to 28.5 months in the 5-6 cycles group (log rank p<0.001). In the multivariate model, the course number of Ra-223 and pre-treatment alkaline phosphatase (ALP) levels were independent risk factors for overall survival. CONCLUSION: Patients who complete 5-6 cycles of Ra-223 had significantly better overall survival than those who didn't. Patients with a lower pre-treatment ALP were more likely to benefit from Ra-223 treatment.

Risk Analysis of Prostate Cancer Development Following Five-alpha Reductase Inhibitor Treatment for Benign Prostate Hyperplasia.

BACKGROUND/AIM: The clinical hazard of prostate cancer development after five-alpha reductase inhibitors (5ARI) treatment among benign prostate hyperplasia (BPH) patients is still controversial. The aim of this study was to evaluate the epidemiological features of BPH patients treated in a single institute to identify risk factors associated with prostate cancer development. PATIENTS AND METHODS: We retrospectively analyzed patients who were diagnosed with BPH and received alpha blockers (AB) only or 5ARI between January 2007 and December 2012 and followed up until death or December 2020. The primary study outcome was prostate cancer and high-grade prostate cancer. RESULTS: Of the 5,122 included patients, 14.9% (762/5,122) received 5ARI during their BPH treatment. The median age, initial prostate specific antigen (PSA) levels and the PSA change were significantly higher in the 5ARI group compared to those of the AB group. The prostate cancer diagnosis rate was higher in the 5ARI group, and the percentage of high-grade prostate cancer was not different between the two groups. In total, 1,715 (33.5%) patients were recorded dead, and the median follow-up period was longer in the 5ARI group. In Cox regression analysis, only age and initial PSA levels were significantly associated with prostate cancer. Late PSA was the only independent factor associated with high-grade prostate cancer development. CONCLUSION: Our real-world data revealed that age, initial PSA, and late PSA levels were associated with prostate cancer and high-grade prostate cancer diagnosis among BPH patients. Furthermore, 5ARI use had no effect on prostate cancer patient survival. However, PSA assessment during follow-up is still required in our institutional practice to avoid delayed diagnosis.

Ursodeoxycholic acid prevention on cholestasis associated with total parenteral nutrition in preterm infants: a randomized trial.

BACKGROUND: Preterm infants with long-term parenteral nutrition (PN) therapy are at risk for cholestasis associated with total parenteral nutrition (PNAC). This study examined the safety and efficacy of ursodeoxycholic acid (UDCA) in preventing PNAC in preterm infants. Our research aimed to investigate the prophylactic effect of preventive oral UDCA on PNAC in preterm infants. METHODS: We compared oral administration of UDCA prophylaxis with no prophylaxis in a randomized, open-label, proof-of-concept trial in preterm neonates with PN therapy. The low-birth-weight preterm infants (< 1800 g) who were registered to the neonatal intensive care unit (NICU) within 24 hours after birth were randomized. The main endpoint was the weekly values of direct bilirubin (DB) of neonates during the NICU stay. RESULTS: Eventually, a total of 102 preterm neonates from January 2021 to July 2021 were enrolled in this prospective study (42 in the UDCA group and 60 in the control group). Notably, the peak serum level of DB [13.0 (12-16) vs. 15.2 (12.5-19.6) µmol/L, P < 0.05)] was significantly lower in the UDCA group than that in the control group without prevention. The peak serum level of total bilirubin (101.1 ± 34 vs. 116.5 ± 28.7 µmol/L, P < 0.05) was also significantly lower in the UDCA group than in the control group. Furthermore, the proportion of patients who suffered from neonatal cholestasis (0.0% vs. 11.7%, P < 0.05) in the UDCA group was significantly lower. CONCLUSION: UDCA prophylaxis is beneficial in preventing PNAC in NICU infants receiving prolonged PN.

Docetaxel Rechallenge Improves Survival in Patients With Metastatic Castration-resistant Prostate Cancer: A Retrospective Study.

BACKGROUND/AIM: Docetaxel has been widely used in metastatic Castration-resistant Prostate Cancer (mCRPC) patients for decades. The purpose of the study was to evaluate the efficacy of docetaxel rechallenge in patients with mCRPC. PATIENTS AND METHODS: We retrospectively compared patients who had received either first-line docetaxel and rechallenge after Androgen Receptor-axis Targeted therapies (ARAT), to those without rechallenge docetaxel. Multivariate cox-regression analysis was used to evaluate survival. RESULTS: Out of the 204 patients with mCRPC enrolled in the study, 24 patients received docetaxel rechallenge and 180 did not. The median overall survival was 50.11 months in the rechallenge group, as compared to 26.36 months in the non-rechallenge group (p of log rank=0.044). In the multivariate model, doxetaxel rechallenge was an independent risk factor for overall survival [hazard ratio (HR)=0.59, 95% confidence interval (CI)=0.32-0.99], together with the performance status score 2 (HR=2.46, 95%CI=1.32-4.58), hormone-sensitive state duration (HR=0.99, 95%CI=0.99-0.999), liver (HR=1.90, 95%CI=1.04-3.47) and brain metastases (HR=2.23, 95%CI=1.26-5.46). The advantage of rechallenge was addressed in the androgen receptor-axis-targeted (ARAT) non-responsive patients (HR=0.36, 95%CI=0.17-0.78). Adverse events were at 29.17% with Grade 3/4 neutropenia and at 20.83% with Grade 1/2 neutropenia in the docetaxel rechallenge group. CONCLUSION: The docetaxel rechallenge improved survival in patients with mCRPC failure of first-line docetaxel and subsequent abiraterone acetate or enzalutamide. Independent predictive factors for overall survival included i) the performance status, ii) hormone-sensitive state duration, iii) liver and iv) brain metastases. Patients non-responsive to ARATs will benefit from docetaxel rechallenge with regards to overall survival.

Macro-Ck type 2 syndrome in prostate adenocarcinoma: Case report and review article.

A 67-year-old male had prostate adenocarcinoma with liver, bone metastases, iliac lymph nodes invasion ever receive hormone and chemotherapy. He was presented to our emergency department with acute onset of mild dizziness and shortness of breath. Elevated CK (1477 U/L) and elevated CK-MB (1602 U/L) was noticed. Electrocardiogram was unremarkable for myocardial ischemia. CK-isoenzyme lab test (electrophoresis) was obtained, which revealed macro CK type 2 accounting for 6.2% of total CK. Type 2 macro CK syndrome was impressed. The falsely elevated CK-MB and macro CK type 2 in serum may be associated with the patient's worsening metastatic disease.

Bi-level Nasal Positive Airway Pressure (BiPAP) versus Nasal Continuous Positive Airway Pressure (CPAP) for Preterm Infants with Birth Weight Less Than 1500 g and Respiratory Distress Syndrome Following INSURE Treatment: A Two-center Randomized Controlled Trial.

The present study aimed to examine the effectiveness of bi-level positive airway pressure (BiPAP) versus continuous positive airway pressure (CPAP) in preterm infants with birth weight less than 1500 g and respiratory distress syndrome (RDS) following intubation-surfactant-extubation (INSURE) treatment. A two-center randomized control trial was performed. The primary outcome was the reintubation rate of infants within 72 h of age after INSURE. Secondary outcomes included bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP) and incidences of adverse events. Lung function at one year of corrected age was also compared between the two groups. There were 140 cases in the CPAP group and 144 in the BiPAP group. After INSURE, the reintubation rates of infants within 72 h of age were 15% and 11.1% in the CPAP group and the BiPAP group, respectively (P>0.05). Neonates in the BiPAP group was on positive airway pressure (PAP) therapy three days less than in the CPAP group (12.6 d and 15.3 d, respectively, P<0.05), and on oxygen six days less than in the CPAP group (20.6 d and 26.9 d, respectively, P<0.05). Other outcomes such as BPD, NEC, ROP and feeding intolerance were not significantly different between the two groups (P>0.05). There was no difference in lung function at one year of age between the two groups (P>0.05). In conclusion, after INSURE, the reintubation rate of infants within 72 h of age was comparable between the BiPAP group and the CPAP group. BiPAP was superior to CPAP in terms of shorter durations (days) on PAP support and oxygen supplementation. There were no differences in the incidences of BPD and ROP, and lung function at one year of age between the two ventilation methods.

Tentative clinical breakpoints and epidemiological cut-off values of nemonoxacin for Streptococcus pneumoniae and Staphylococcus aureus isolates associated with community-acquired pneumonia.

OBJECTIVES: To determine the minimum inhibitory concentration (MIC) distribution, epidemiological cut-off (ECOFF) values and clinical breakpoints (CBPs) of nemonoxacin, a non-fluorinated quinolone, for community-acquired pneumonia (CAP)-related Streptococcus pneumoniae and Staphylococcus aureus. METHODS: We pooled the susceptibility and clinical data of CAP patients enrolled in five clinical trials conducted in three countries from 2006 to 2017. Published pharmacokinetic (PK) profiles of oral (500 mg) and intravenous (IV) (500, 650 and 750 mg) nemonoxacin formulations and pharmacodynamic (PD) parameters of the two aforementioned CAP-related Gram-positive cocci (GPC) were used to determine plausible CBPs. Moreover, nemonoxacin MIC distributions of CAP-relatedS. pneumoniae (n = 1800) and S. aureus (n = 2000) isolates were obtained to evaluate ECOFF values using a visual estimation approach and ECOFFinder. RESULTS: More than 92% of patients with CAP caused byS. pneumoniae or S. aureus with nemonoxacin MICs ≤ 0.25 mg/L presented positive clinical and microbiological outcomes. The ECOFF, MIC90 and MIC99 values of nemonoxacin were, respectively, 0.06, 0.125 and 1 mg/L for S. pneumoniae and 0.125, 1 and 8 mg/L for S. aureus. Based on differences in the PK profiles of oral and IV formulations, PD parameters of nemonoxacin for these CAP-GPC and clinical in vivo efficacy data, tentative CBPs of 0.5, 0.5 and 1 mg/L, respectively, were established for the 500 mg oral and 500 mg and 750 mg IV nemonoxacin formulations for S. pneumoniae, and 0.25, 0.5 and 1 mg/L for S. aureus. CONCLUSION: This study provides plausible nemonoxacin CBPs for two important CAP-GPC.

Geriatric Nutritional Risk Index as a Prognostic Marker for Patients With Metastatic Castration-Resistant Prostate Cancer Receiving Docetaxel.

Purpose: To investigate the prognostic efficacy of the Geriatric Nutritional Risk Index (GNRI) in patients with metastatic Castration-resistant Prostate Cancer (mCRPC) receiving docetaxel as the first line of treatment. Methods: We retrospectively reviewed patients with mCRPC and receiving first line docetaxel in Taichung Veterans General Hospital from 2006 to 2012. The GNRI was calculated using serum albumin and body mass index, with a poor nutritional status defined as GNRI <92.0. Multivariate Cox-regression analysis was used to evaluate the risk of survival. Results: One-hundred seventy patients with mCRPC were included. One-hundred twenty-five patients were of normal nutritional status (GNRI ≥92) and 45 patients were of poor nutritional status (GNRI <92). The cumulative docetaxel dosage was 600 (360-1,185) mg in the normal nutritional status group and 360 (127.5-660) mg in the poor nutritional status group (p < 0.001). The median overall survival from mCRPC was 30.39 months in the good nutritional status group and 11.07 months in the poor nutritional status group (p of log rank <0.001). In a multivariate model, poor nutritional status was an independent risk factor in overall survival (Hazard Ratio [HR] = 5.37, 95% Confidence Interval [CI] 3.27-8.83), together with a high metastatic volume (HR = 4.03, 95% CI 2.16-7.53) and docetaxel cumulative dosage (HR = 0.999, 95% CI 0.999-0.9998). Conclusion: Poor nutritional status with a GNRI <92 is associated with shorter progression free survival and overall survival in mCRPC patients treated with docetaxel. Metastatic volume and cumulative docetaxel dosage are also independent prognostic factors in overall survival.

Surgical Drain-Related Intestinal Obstruction After Robot-Assisted Laparoscopic Radical Prostatectomy in Two Cases.

Background: Drainage tubes are almost always routinely used after a laparoscopic or robot-assisted radical prostatectomy and pelvic lymphadenectomy to prevent urinoma formation and lymphoceles. They are seldom of any consequence. We present our unique experience of bowel obstruction resulting from the use of pelvic drains. Case Presentation: We are reporting on two prostate cancer cases with rare postoperative complications. Each of them received robot-assisted laparoscopic radical prostatectomy and bilateral pelvic lymph node dissection and subsequently developed ileus and bowel obstruction. Series follow-up images suggested the bowel obstruction was related to their drainage tube. No evidence of urine leakage or intestine perforation was found based on drainage fluid analysis. We performed exploratory laparotomy in the first patient and found drainage tube kinking with the terminal ileum and adhesion band. The drainage tube was removed and patient recovery occurred over the following days. In the second case, the patient experienced bowel obstruction for 4 days after surgery. Based on our experience in the first case, and a drainage fluid survey showing no evidence of urine leakage, we removed the drainage tube on the morning of the 4th day, giving the patient a dramatic recovery with flatus and stool passage occurring in the afternoon. Both of the patients recovered well in hospital and during regular follow-up. Conclusion: To best of our knowledge, despite there being certain case reports regarding drainage tube ileus in colorectal and bowel surgery, we have reported here on the first two cases of small bowel obstruction as a complication arising from the abdominal drainage tube used in robot-assisted urology surgery.