Significance of baseline bone markers on disease progression and survival in hormone-sensitive prostate cancer with bone metastasis.

PURPOSE: This study evaluated the baseline patient characteristics associated with the time to biochemical progression and overall survival in patients who participated in a phase II trial on zoledronic acid combined with the initial androgen-deprivation therapy for treatment-naïve bone-metastatic prostate cancer. METHODS: Patients received zoledronic acid 4 mg intravenously every 4 weeks for up to 24 months, concomitantly started with bicalutamide 80 mg orally every day and goserelin acetate 10.8 mg subcutaneously every 12 weeks. RESULTS: A total of 53 Japanese patients were enrolled between July 2008 and April 2010, and 52 patients were evaluable. Median follow-up period was 41.6 months. Updated median time to biochemical progression was 25.9 months (95 % confidence interval 14.5-49.9). Higher serum bone-specific alkaline phosphatase was an independent risk factor for time to biochemical progression based on multivariate analysis (hazard ratio 6.51; 95 % confidence interval 2.71-15.62; P < 0.001). Median time to biochemical progression for patients with serum bone-specific alkaline phosphatase level higher than 26 µg/L was 12.7 months. Multivariate analysis indicated that higher serum C-terminal telopeptide of type I collagen independently increased the risk of death (hazard ratio 9.62; 95 % confidence interval 2.11-43.89; P = 0.003). Median overall survival for patients with serum C-terminal telopeptide of type I collagen level higher than 8.0 ng/ml was 31.1 months. CONCLUSIONS: Baseline bone markers can be useful as predictors for disease progression and survival time in patients with bone metastasis from treatment-naïve prostate cancer treated with upfront zoledronic acid concomitantly started with androgen-deprivation therapy.

Early administration of non-vitamin K antagonist oral anticoagulants for acute ischemic stroke patients with atrial fibrillation in comparison with warfarin mostly combined with heparin.

BACKGROUND: This study evaluated the rates of new lesions on diffusion-weighted images (DWIs) of magnetic resonance imaging (MRI) and hemorrhagic transformation (HT) during 2 weeks after acute ischemic stroke (AIS) in patients with atrial fibrillation (Af) who were given one of the non-vitamin K antagonist oral anticoagulants (NOACs); this was then compared with those who were given warfarin. METHODS AND RESULTS: Consecutive AIS patients with Af were enrolled between January 2008 and June 2013, and those selected were patients who had a MRI that included DWIs both on admission and after 2 weeks, and those given only wafrarin (warfarin group) or only one of the NOACs (NOAC group) within 2 weeks of admission. Of all 257 enrolled patients, 50 patients were selected for the NOAC group (median age of 80.0 years) and 125 patients for the warfarin group (median age of 80.0 years). Both NOAC and warfarin were started at a median of the second day after admission. There was no significant difference in the rates of new lesions on DWIs (26.0% vs. 28.0%, P=0.7888) and HT (30.0% vs. 39.2%, P=0.2536) between the NOAC and warfarin groups. The NOAC group had a lower rate of concomitant use of heparin (44.0% vs. 92.8%, P<0.0001) than the warfarin group. CONCLUSIONS: This study suggests that NOACs are suitable for AIS patients with Af, perhaps even better than warfarin, given their simplicity.

Phase II trial of zoledronic acid combined with androgen-deprivation therapy for treatment-naïve prostate cancer with bone metastasis.

BACKGROUND: The efficacy of zoledronic acid in patients with treatment-naïve prostate cancer is unclear. We conducted a phase II study to investigate the benefits of combined zoledronic acid and androgen deprivation therapy in treatment-naïve prostate cancer with bone metastasis. The primary endpoint was skeletal-related event-free survival at 24 months. METHODS: Subjects were treatment-naïve patients with histologically confirmed adenocarcinoma of the prostate and radiological evidence of bone metastasis. Treatment consisted of bicalutamide 80 mg daily, goserelin acetate 10.8 mg every 12 weeks, and zoledronic acid 4 mg every 4 weeks. Zoledronic acid was continued for 24 months. RESULTS: Of the patients enrolled between July 2008 and April 2010, 52 were included in the analyses. The median age of the patients was 72 years. The median baseline prostate-specific antigen level was 249.4 ng/mL. The median follow-up period was 33.3 months. The 24-month skeletal-related event-free survival rate was 84.4 % (95 % confidence interval 71.2-91.9). The median time to prostate-specific antigen progression was 25.9 months (95 % confidence interval 14.7-36.3). The median overall survival time was not reached. Improvement in pain or maintenance of no pain during the first 12 weeks was observed in 70 % of patients and the extent of bone disease was decreased in 10 % of patients at 12 months. Grade 3 osteonecrosis of the jaw was observed in three patients (5.8 %). CONCLUSION: Zoledronic acid concomitant with androgen deprivation therapy as initial treatment in patients with treatment-naïve prostate cancer with bone metastasis resulted in an encouraging skeletal-related event-free survival rate at 24 months.

Can early effective anticoagulation prevent new lesions on magnetic resonance imaging in acute cardioembolic stroke?

BACKGROUND: The timing of warfarin administration for acute ischemic stroke (AIS) patients with atrial fibrillation (Af) has not been established. We hypothesized that achieving targeted prothrombin time and international normalized ratio (PT-INR) at 2 weeks could prevent AIS patients with Af from developing a new lesion on diffusion-weighted magnetic resonance imaging (DW-MRI). METHODS: Of consecutively enrolled AIS patients with Af between 2008 and 2011, we selected the patients who were given warfarin within 2 weeks of admission and had DW-MRI and blood test for PT-INR both on admission and at 2 weeks. Warfarin was started as early as possible and heparin was administered until the targeted PT-INR (2.0-3.0 for patients aged <70 years or 1.6-2.6 for those aged ≥70 years) was achieved. RESULTS: One hundred and twenty-three patients were selected, consisting of 88 patients without a new lesion and 35 patients with a new lesion. Patients with a new lesion had a significantly higher median score on National Institutes of Health Stroke Scale (11.0 vs. 5.5, P = .0053), a lower rate of achieving targeted PT-INR at 2 weeks (25.7% vs. 48.9%, P = .0190), and a lower median dosage of warfarin at 2 weeks (2.0 mg vs. 2.5 mg, P = .0209) than patients without a new lesion. Multivariate logistic regression analysis showed that failure to achieve targeted PT-INR (P = .0298) was significantly associated with the occurrence of a new lesion. CONCLUSIONS: Our findings suggest that achieving targeted PT-INR at 2 weeks by using warfarin prevents new lesions in AIS patients with Af.

Nucleic acid-extracted torula yeast from the paper industry as a protein feed for ruminants: A comparison with soybean meal.

We compared nucleic acid-extracted torula yeast (NTY) with soybean meal (SBM) to evaluate NTY as a potential protein feed for ruminants in a metabolic trial using four castrated male goats. NTY was replaced isonitrogenously with SBM at a 25% crude protein (CP) level on a dry matter (DM) basis. NTY has 55% CP and 74% total digestive nutrients on DM. Absorbed N was lower on the NTY diet, but since the urinary N excretion was lower on the NTY diet, no significant between-diet difference in retained N was observed. The efficiency of N utilization (retained N/absorbed N) was significantly higher on the NTY diet. The Lys and Met contents (presumed limiting amino acids for dairy cattle) were higher in NTY than SBM, which may be why N utilization efficiency was higher for the NTY diet. Ruminal ammonia-N and blood serum N were lower on the NTY diet, suggesting that NTY has more rumen undegradable protein than SBM. There was no significant between-diet difference in the visceral disorder indicators or antioxidant activities. Our results indicate that NTY is a safe protein feed with a high CP ratio and high-quality amino acid profile for ruminants that is equivalent to SBM.

Sunflower cake versus soybean meal and alfalfa for nitrogen utilization when crude protein and non-fiber carbohydrate levels are equivalent.

The reported efficiency of N usage by sunflower cake (SFC) was inferior to that of soybean meal (SBM) in a study in which the non-fiber carbohydrate (NFC) content was lower in the SFC diet. Here, we adjusted crude protein (CP) and NFC levels to near-equivalence among three diets containing SFC or SBM for four non-lactating Holstein cows. Alfalfa hay was also added to the comparison. The results demonstrated that the total digestible nutrient contents were not significantly different among the diets. Intake N, fecal N, absorbed N, urinary N, and retained N did not differ significantly among the diets. The efficiency of N usage in the body (retained N/absorbed N) did not differ significantly among the diets. No between-diet difference was observed in the protein- and energy-related ruminal and blood properties, including the estimated microbial protein synthesis in the rumen. These results suggest that regardless of the quality and balance of amino acids in a feed, the efficiency of N usage can be improved by a supply of digestible carbohydrates, which leads to an increase in ruminal microbial protein.

[Analysis of prognostic factor in 52 castration-resistant prostate cancer treated with docetaxel].

The prognostic factor was retrospectively analyzed in 52 castration-resistant prostate cancer treated with docetaxel (DTX) in our institutions from April, 2006 to August, 2009. The treatment outcomes were decided with prostate specific antigen (PSA) progression-free survival and overall survival. These were calculated by Kaplan-Meier methods and tested with Log-rank test. Median PSA progression-free survival was 8.8 months and median overall survival was 24.1 months. Prognostic factors on PSA progression were PSA value before DTX treatment and rate of PSA decrement after DTX treatment. Prognostic factors on overall survival were Gleason score (GS), PSA value before DTX treatment, rate of PSA decrement after DTX treatment and positive of bone metastasis in Log-rank test. Odds ratio of PSA ≧20 ng/ml before DTX treatment was 2.99 and PSA decreasing rate < 30% was 3.65. These were statistically significant (p < 0.001) risk factors in the overall survival.

Ruminal protein degradability of sunflower cake, and effects of feeding sunflower cake on nutrient digestion, nitrogen balance, rumen fermentation, and blood metabolites compared with soybean meal.

The ruminal degradation parameters of sunflower cake (SFC), a by-product left after the mechanical extraction of oil from sunflower seeds, were estimated in an in situ experiment using a cow. And also the effect of feeding SFC on nutrient digestibilities, digestible energy, nitrogen balance, and ruminal and blood properties were investigated in a feeding trial using four Shiba goats compared isonitrogenously with soybean meal (SBM). The in situ results demonstrated that the SFC had high soluble protein (>70%) with 97% total degradable protein. The feeding trial revealed that the SFC had 85% crude protein digestibility and 65% total digestible nutrients on a dry matter basis in which the low carbohydrate digestibilities offset the advantage of high digestible fat (9.9%). The nitrogen efficiency (retained N/intake N) was lower for SFC than SBM, probably because of an inferior biological value of amino acids in SFC. Among the ruminal and blood properties, only the total ruminal acid concentration and blood urea nitrogen (BUN) differed significantly between the diets: The SFC diet showed lower values than the SBM diet. These findings indicate that SFC can safely replace SBM.

Analysis of fecal nutrients and particle size in captive proboscis monkeys (Nasalis larvatus) fed seasonal dietary foliage at a Japanese zoo.

One male and three female captive proboscis monkeys (Nasalis larvatus) were used as test animals to compare fecal nutrients after being fed seasonal foliage. Foliage and fecal samples were collected during three seasons (spring, summer, and winter). We analyzed crude ash (CA), ether extract (EE), crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF), and acid detergent lignin (ADL). In addition to the above components, for the fecal samples, we examined total fecal nitrogen (TFN), nitrogen in fecal NDF (NDF-N), metabolic fecal nitrogen (MFN), and particle size distribution (MPS). Seasonal differences in foliage components were observed, with NDF and ADF being lowest in spring (p < 0.05). Fecal NDF and ADF also tended to be lowest in spring. Further, the distribution of fecal particle size indicated that MPS tended to increase in winter. The mean fecal NDF content (47.4%) for all three seasons measured in this study was as much as 1.3 times lower than previously reported values in free-ranging specimens. These data provide useful information that can be used to find some suitable food items for the endangered highly folivorous monkeys in captivity.

Digestive, fermentative, and physical properties of pineapple residue as a feed for cattle.

The intake, digestion, and ruminal fermentation properties; the antioxidative activity; and the physical effectiveness of pineapple residue (PR) from the cut-fruit industry as a feed for cattle were investigated. Four nonlactating Holstein cows were fed a basal diet and diets with 1.4- and 3.6-kg dry matter (DM)/day of PR (low-PR and high-PR diets, respectively). The DM digestibility and total digestible nutrients were 71% and 70%, respectively. Ruminal pH, volatile fatty acids, and ammonia-N did not differ among the diets. The numbers of total viable, amylolytic, cellulolytic, and methanogenic bacteria and protozoa, and microbial protein synthesis in the rumen also did not differ significantly. Blood triglyceride, nonesterified fatty acids, urea nitrogen, and aspartate transaminase were lower in the high-PR diet. Feeding PR did not affect blood malondialdehyde, although PR has a higher antioxidative value than other commonly used feeds. The particle distribution of PR satisfied the recommended range for haylage. The chewing time for ingestion and rumination did not change with PR content, and the roughage value index of PR was 57-min/kg DM. These results suggest that PR has good intake and digestion properties and satisfactory physical effectiveness. Even a high-PR-content feed unlikely induces the risk of ruminal acidosis.

Effect of high-concentrate corn grain diet-induced elevated ruminal lipopolysaccharide levels on dairy cow liver function.

A high-concentrate diet destroys gram-negative bacteria in the cattle rumen, leading to elevated ruminal lipopolysaccharide (LPS) levels. LPS causes liver inflammation through the hepatic portal vein but little is known about the effects of rumen-derived LPS on liver function and the reproductive organs. In this study, we determined the effect of increasing rumen fluid LPS levels on liver function and genital LPS levels. Cows were assigned to control (CON; n=5) and high-concentrate diet (HC; n=7) groups. We observed that the ruminal LPS and haptoglobin (Hp) levels were significantly higher and albumin levels were lower in the HC group than in the CON group. In the HC group, The Hp levels and aspartate transaminase (AST) activity were significantly higher and the total cholesterol levels were significantly lower after high-concentrate diet feeding than before feeding. No differences were observed in LPS levels in the peripheral veins, hepatic veins, hepatic portal vein, uterine perfusate, and follicular fluids between the groups. In all samples, the LPS level in the hepatic portal vein blood positively correlated with the AST activity and serum amyloid A level. In conclusion, our results indicate that high-concentrate diets do not have a direct effect on the reproductive organs upon a moderate ruminal LPS level increase. However, an increased ruminal LPS influx into the liver might affect negatively liver function.

[A case of advanced adenocarcinoma of the ethmoid sinus treated by chemoradiation with S-1].

We report a case of advanced adenocarcinoma in the left ethmoid sinus invading the frontal sinus, the frontal skull base and the orbits(T4bN0M0 and Stage IVB). With the goal of functional preservation, we carried out radiation therapy with total 60 Gy irradiation and chemotherapy with S-1 80 mg/body/day before a radical operation. The tumor clinically disappeared without surgical treatment, and there was no sign of recurrence for 2.5 years. When we decide the treatment policy for advanced adenocarcinoma of the ethmoid sinus, chemoradiotherapy wit S-1 might be one of the effective treatments before radical operation to control the disease with preservation of functions.

Evaluation of clinical significance of decompressive suboccipital craniectomy on the prognosis of cerebellar infarction.

OBJECTIVE: The decision of whether and/or when to treat cerebellar infarction surgically remains controversial. We investigated the effectiveness of decompressive suboccipital craniectomy (DSC) for treating cerebellar infarction and the prognostic factors that affect the surgical results. METHODS: From October 2006 to June 2017, a total of 14 consecutive patients (12 men, 2 women; mean±SD age 65±12 years, range 42-84 years) were admitted to our hospital and underwent DSC at the time of admission or during their hospitalization. Inclusion criteria were (1) a level of consciousness below Glasgow Coma Scale (GCS) 13, and/or (2) brainstem compression and/or obstructive hydrocephalus caused by brain edema due to cerebellar infarction. Ventricular drainage was performed simultaneously or later, according to the surgeon's decision. RESULTS: At the 90-day point, 12 of the 14 patients (85.7%) had survived, 10 (71.4%) of whom were independent (modified Rankin scale ≤2). Four (28.6%) were either completely dependent or dead. Comparisons between good and poor prognoses showed that the factors affecting the prognosis were lesions other than the cerebellar infarction (p<0.01) and/or obstructive hydrocephalus (p<0.05). CONCLUSIONS: Early DSC should be considered for treating cerebellar infarction in patients with GCS 13 or worse. A poor prognosis is inevitable in patients whose infarction is combined with other location than the cerebellum but in those who already have obstructive hydrocephalus at the time of surgery.

In situ ruminal degradation and in vitro fermentation characteristics, and antioxidative activities of the lotus rhizome.

We evaluated the lotus rhizome as a potential ruminant feed by investigating its compositional properties, in situ degradation profile and in vitro fermentation characteristics with ruminal microbes, in comparison with cereal grains (corn, barley and wheat). The antioxidative activities in the lotus rhizome were also estimated. The soluble fraction of dry matter in lotus tuber was >70%, which was higher than those in the grains. The insoluble fraction in lotus tuber was not degraded by ruminal microbes in accord with a first-order reaction. In an in vitro experiment, lotus tuber showed lower fermentation at 8 hr compared to the grains, but exhibited higher productions of gas and VFA at 48 hr along with a lower lactate and higher pH. The lower value of final lactate production in lotus tuber, indicating the metabolic capacity for lactate utilization retained, suggests a lower risk of ruminal acidosis compared to grains. Lotus rhizome had high antioxidant activities, with the foliar bud showing the strongest ferric reducing antioxidant power, followed in order by the apical bud, node, residual tuber, edible tuber, and nodal root. For ruminants, the lotus rhizome could thus be not only an energy feed but also the source of natural antioxidants.

Effects of rumen-protected methionine on milk production in early lactation dairy cattle fed with a diet containing 14.5% crude protein.

We evaluated the influence on milk production of feeding early lactation cows a diet that included 14.5% crude protein (CP) and that did not meet methionine (Met) requirements or that met them by supplying rumen-protected Met (RPMet). Thirty-nine multiparous Holstein cows were allocated into two groups. For 15 weeks after calving, each group was fed one of the two total mixed rations, Control (n = 20) or Treatment (n = 19). The Treatment group received added RPMet at 0.034% (8 g/day) of the Control diet on dry matter basis. The adequacies of Met for the Control and Treatment groups were 96% and 106%, respectively, and for other amino acids, >110%. The CP level (14.5%) was 1 percentage point lower than that recommended by the Japanese Feeding Standard (2006). No between-group differences were found in milk yield (40 kg/day), milk composition, plasma profile, rumen fermentation, nitrogen balance, or cow health. Met intake and the amount of rumen-undegradable feed Met were higher in the Treatment group (p < 0.05). Microbial Met and total metabolizable Met did not differ between groups. Supplying RPMet in a 14.5% CP diet during early lactation did not dramatically affect milk production, because the amount of total metabolizable Met was unchanged.

Dural arteriovenous fistula presenting with acute subdural haematoma showing impending cerebral herniation.

A dural arteriovenous fistula (DAVF) presenting with acute subdural haematoma (ASDH), which were not related to head injury, is rare. A 61-year-old woman was transported by ambulance because of deterioration of consciousness. On admission, she was comatose with anisocoria. Emergent CT demonstrated a severe midline shift associated with a left ASDH and an additional left occipital intracerebral haematoma, both of which had no continuity with each other. MRI showed flow void signs in the left occipital lobe. Because of the impending cerebral herniation, an emergent evacuation of the ASDH and external decompression was performed. Subsequent evaluation revealed a DAVF at the left occipital convexity near the confluence with retrograde leptomeningeal venous reflux and venous ectasia (Cognard type III DAVF). The patient underwent endovascular treatment for the DAVF involving transarterial embolisation using coils and N-butyl cyanoacrylate with complete obliteration. Her further clinical course was uneventful and discharged after cranioplasty.

[Abscess of corpus cavernosum: two case reports].

Case 1: A 50-year-old man was admitted to our hospital complaining of miction pain and fever up. Although there was remission by antibiotic treatment, symptoms recurred. Computed tomographic scan revealed swelling of scrotum and penis. Therefore, the patient was diagnosed with abscess of corpus cavernosum. The patient underwent debridement. Although symptoms remissed, he had erectile dysfunction. Case 2: A70-year-old man was admitted to our hospital complaining of perineal painful swelling. The patient was diagnosed with abscess of corpus cavernosum by computed tomographic scan. The patient underwent debridement, and symptoms remissed. If the patient is admitted to hospital complaining of miction pain and fever up, abscess of corpus cavernosum should be suspected.

Zoledronic acid combined with androgen-deprivation therapy may prolong time to castration-resistant prostate cancer in hormone-naïve metastatic prostate cancer patients - A propensity scoring approach.

OBJECTIVE: To clarify the oncological benefit of zoledronic acid for hormone-naïve metastatic prostate cancer, patient outcome of androgen deprivation therapy with zoledronic acid (ADT + Z) and androgen deprivation therapy alone (ADT) was compared. METHODS: Fifty-two patients with pathologically confirmed metastatic prostate cancer were prospectively enrolled and treated with combined androgen blockade (goserelin and bicalutamide) with zoledronic acid (4 mg every 4 weeks for 24 months). A propensity score-match with logistic regression analysis was applied to select 50 pair-matched cohorts (both from ADT + Z and from historical control cohorts who had undergone ADT alone), and patient outcomes were compared. RESULTS: Patients with ADT + Z had significantly longer time to progression (TTP) than those with ADT (median TTP; 24.2 vs. 14.0 months, p = 0.0092), while no significant difference of overall survival between two groups (p = 0.1502). Multivariate analysis for biochemical recurrence revealed treatment with ADT was the sole independent prognostic factor (HR: 1.724, 95% CI: 1.06-2.86, p = 0.0297). CONCLUSION: Combination of zoledronic acid with ADT may prolong time to castration resistant prostate cancer.

Nutritional values and antioxidative activities of whole peanuts and peanut skins for ruminant feeds.

This study was conducted to investigate the nutritive values of two peanut by-products, nonstandardized whole peanuts and peanut skins, along with their effects on microbial growth and fermentation in the rumen, their roughage values, and their antioxidative activities by a digestion trial using four goats. The experimental rations were alfalfa haycube (basal ration), 85% alfalfa with 15% whole peanuts, and 70% alfalfa with 15% whole peanuts and 15% peanut skins. The ether extracts and crude protein in whole peanuts were 47% and 27% on a dry matter basis (DM) both with over 90% of digestibilities, resulting in total digestive nutrients (TDN) of 140%. Peanut skins also had a high energy value with 91% of TDN. Ruminal concentrations of total volatile fatty acids (VFA) and acetic acid decreased in the rations containing the peanut by-products, but the NDF digestibility and ruminal microbial protein estimated from urinary purines was not altered by feeding the peanut by-products. Plasma oxidative stress maker, malondialdehyde, tended to be lower when peanut skins were supplemented. Whole peanuts and peanut skins could be used as high-energy and high-protein diets for ruminants, and peanut skins would be expected as a feed having antioxidant functions.

[Two cases of spontaneous intracranial hypotension associated with chronic subdural hematoma only treated with burr hole irrigation of the hematomas].

We reported two cases of spontaneous intracranial hypotension (SIH) associated with bilateral chronic subdural hematoma (CSDH). The patients presented with severe positional headache, aggravated by sitting or standing. Neither spinal surgery nor lumbar-tap had been performed in these patients. They were diagnosed as SIH with bilateral CSDH. Headache was aggravated and CSDHs volume increased despite conservative therapy. However, after a burr hole irrigation of hematoma, not only CSDHs but also the symptoms with SIH were completely resolved and there was no recurrence. We demonstrated that burr hole irrigation for CSDH associated with SIH might completely resolve the SIH symptom in some cases, as in the present report. The mechanism of this phenomenon was discussed.