Long-term efficacy and safety of a combination of sabal and urtica extract for lower urinary tract symptoms—a placebo-controlled, double-blind, multicenter trial

The efficacy and tolerability of a fixed combination of 160 mg sabal fruit extract WS 1473 and 120 mg urtica root extract WS 1031 per capsule (PRO 160/120) was investigated in elderly, male patients suffering from lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia in a prospective multicenter trial. A total of 257 patients (129 and 128, respectively) were randomized to treatment with PRO 160/120 or placebo (127 and 126 were evaluable for efficacy). Following a single-blind placebo run-in phase of 2 weeks, the patients received 2×1 capsule/day of the study medication under double-blind conditions over a period of 24 weeks. Double-blind treatment was followed by an open control period of 24 weeks during which all patients were administered PRO 160/120. Outcome measures for treatment efficacy included the assessment of the patients LUTS by means of the I-PSS self-rating questionnaire and a quality of life index as well as uroflow and sonographic parameters. Using the International Prostate Symptom Score (I-PSS), patients treated with PRO 160/120 exhibited a substantially higher total score reduction after 24 weeks of double-blind treatment than patients of the placebo group (6 points vs 4 points; P=0.003, one tailed) with a tendency in the same direction after 16 weeks. This applied to obstructive as well as to irritative symptoms, and to patients with moderate or severe symptoms at baseline. Patients randomized to placebo showed a marked improvement in LUTS (as measured by the I-PSS) after being switched to PRO 160/120 during the control period (P=0.01, one tailed, in comparison to those who had been treated with PRO 160/120 in the double-blind phase). The tolerability of PRO 160/120 was comparable to the placebo. In conclusion, PRO 160/120 was clearly superior to the placebo for the amelioration of LUTS as measured by the I-PSS. PRO 160/120 is advantageous in obstructive and irritative urinary symptoms and in patients with moderate and severe symptoms. The tolerability of the herbal extract was excellent.     

Gene expression analysis of human tissue from patients with cardiomyopathies: a new tool for guiding therapies in the future?

The complete sequencing of the human genome led to the development of a number of new molecular technologies. DNA microarrays represent an exciting new tool for gene expression analysis in human tissue. Measurements of the expressions of many thousands of genes in parallel is possible now. Microarrays may be used for various applications in medicine. They can be used to find novel prognostic and predictive markers as well as new disease classifications into clinically relevant subgroups. While there has been great progress in cancer research in this field, there are significantly less expression data available concerning the heart. In order to identify genes and pathways involved in the pathogenesis of cardiomyopathies, we have looked recently for alterations at cellular and molecular levels in heart tissue from cardiomyopathy patients. We showed that a special group of genes is differentially regulated in dilated cardiomyopathy. The first results in hypertrophic cardiomyopathy also showed similar findings. The surgeon's role in the clinical application of gene expression profiling is crucial. He provides a link between the patient and the laboratory scientists playing a significant role in focusing research on the clinically relevant problems. Gene expression profiles may help to better characterize the course and prognosis of the individual patient in the future. The long-term goal is to find a tool that will help to guide medical and surgical therapies in cardiomyopathies and other heart diseases.     

Speedy elimination of ureterolithiasis in lower part of ureters with the alpha 1-blocker – Tamsulosin

Background:Alpha – 1 blockers decrease the tension and release the spasm of smooth muscles and thus lessen the obstruction and irritation symptoms in the lower urinary tract (LUTS). They make a faster passing of calculi from the terminal part of the ureters possible.Objectives:The goal of this study was to objectively assess the improvement of difficulties caused by obstructions in ureterolithiasis localized in the lower part of the ureters of 104 randomly chosen patients (pts.) in a double-blind study.Methods:During a period of 2 and half years (June 1999–January 2002) 104 pts. suffering from ureterolithiasis of the lower urinary tract were treated and observed. Patients were divided into two groups: A (n:53; later only 51 were evaluated) which was subjected to standard treatment and group B (n:51) where the standard treatment was supplemented by the alpha – 1 blocker. As alpha – 1 blocker one capsule of Tamsulosin /OMNIC 0.4 / was administered daily.Results:With alpha – 1 blocker, we have registered a more speedy passing of calculi from the terminal parts of ureters in 17.6% of pts. Recurrence of renal colics was less frequent and occurred in one of eight pts. as compared with group A (without the alpha – 1 blocker) where a recurrence of the renal colic was observed in about every fifth pts. In group A (n:51), 62.8% of the pts. passed the calculi, whereas in group B (n:51), where standard treatment was supplemented by the administration of the alpha – 1 blocker Tamsulosin, this percentage increased to 80.4%.Conclusion:The treatment by alpha – 1 blockers considerably decreased not only LUTS but also helped to accelerate the passing of minor calculi from the terminal parts of the ureters of 80.4% of pts. It seems that alpha – 1 blockers potentiate the spasmoanalgetic action of drugs used in standard methods of treatment.     

HCC recurrence in HCV-infected patients after liver transplantation: SiLVER Study reveals benefits of sirolimus in combination with CNIs – a post-hoc analysis

Factors affecting outcomes in liver transplant (LTx) recipients with hepatocellular carcinoma (HCC) and hepatitis C viral (HCV) infection include the choice of immunosuppression. Here, we analyzed the HCV⁺ subgroup of patients from the randomized controlled, international SiLVER Study. We performed a post hoc analysis of 166 HCV⁺ SiLVER Study patients regarding HCC outcome after LTx. Control patients (group A: n = 88) received mTOR inhibitor (mTORi)-free, calcineurin inhibitor (CNI)-based versus sirolimus-based immunosuppression (group B: n = 78). We found no significant difference regarding HCV-RNA titers between group A and B. Since no effect in group B could be due to variable sirolimus dosing, we split group B into patients receiving sirolimus-based immunosuppression + CNIs for >50% (B1; n = 44) or <50% (B2; n = 34) of the time. While there remained no difference in HCV-RNA titer between groups, HCC recurrence-free survival in group B1 (81.8%) was markedly better versus both group A (62.7%; P = 0.0136) and group B2 (64.7%; P = 0.0326); Interestingly, further subgroup analysis revealed an increase (P = 0.0012) in liver enzyme values in group B2. Taken together, in HCV-infected patients with HCC and LTx, mTORi immunosuppression + CNIs yields excellent outcomes. Unexpectedly, higher levels of liver inflammation and poorer outcomes occur with mTORi monotherapy in the HCV⁺ subgroup.     

Is there still a place for arthrodesis in the surgical treatment of basal joint osteoarthritis of the thumb?

Despite the obvious success of arthroplasty trapeziectomy with or without interposition and prosthesis--in the treatment for trapeziometacarpal osteoarthritis, one may question the value of an arthrodesis in particular situations. In most reported series the outcome is reasonably successful, but when comparing the results of arthrodesis with arthroplasty, there is convincing evidence that the latter gives better outcomes. Considering the overall complication rate, and more specifically the incidence of nonunion after trapeziometacarpal fusion, it can be reasonably concluded that the latter should be reserved for specific indications.     

Is there a role for targeted therapies in the collecting ducts of Bellini carcinoma? Efficacy data from a retrospective analysis of 7 cases

Introduction

Though uncommon, the collecting duct carcinoma (CDC) of Bellini is a very aggressive primary renal tumour occurring in less than 1% of all renal cell carcinoma (RCC) cases. This rare subtype was always excluded from the prospective trials with targeted therapies. Few data so far available concern the subgroup analyses from the expanded access programs with sorafenib and sunitinib, and from temsirolimus randomized study.

Patients and methods

From December 2004 to May 2010, 333 patients with advanced RCC have been treated in our Institution with targeted therapies: of these, 7 (2.6%) were affected by CDC. General characteristics, symptoms, pathological features, treatments and patients’ outcome were recorded.

Results

All patients affected by CDC received targeted agents as first-line therapy: more precisely, 4 patients were treated with sorafenib, 2 with temsirolimus and 1 with sunitinib. After progression 2 patients received a second-line treatment with sunitinib. No patients were alive at 5?years. Five patients developed early progression of disease with a very short 4-month survival, while 2 cases had a long-lasting disease control with an overall survival time accounting for 49 and 19?months, respectively. Treatment-related adverse events were manageable consisting of fatigue, diarrhoea, hand–foot syndrome, hypertension and anemia, the latter being the most frequent. No treatment discontinuations due to adverse event were needed.

Conclusions

This investigation shows that targeted agents are safe, displaying some degree of activity in CDCs: therefore, they could be considered as an alternative in patients not eligible to chemotherapy regimens. Further studies including biomarkers as predictive factors of tumour biology and clinical features are required to improve the management of this challenging disease.     

A phase II clinical trial of oral bropirimine in combination with intravesical bacillus Calmette-Guérin for carcinoma in situ of the bladder: a Southwest Oncology Group Study

OBJECTIVES: To estimate the probability of response when intravesical bacille Calmette-Guérin (BCG) is given in combination with oral bropirimine for bladder carcinoma in situ, and to evaluate toxicity when the 2 agents are combined. METHODS: A total of 51 patients with histologic evidence of carcinoma in situ and no prior treatment with BCG or bropirimine were enrolled in a cooperative group multicenter phase II trial. Initial treatment included Tice BCG 50 mg weekly for 6 weeks and oral bropirimine 3.0 g/day for 3 consecutive days each week for 12 weeks. Response was assessed after 12 weeks by cystoscopy, biopsy, and barbotage cytology. Most patients received a second course followed by an identical assessment. Toxicity was recorded according to the Southwest Oncology Group toxicity criteria. RESULTS: A total of 51 patients were enrolled and treated. There were 42 patients who were eligible and valuable for response and toxicity. There were 28 complete responders (67%, 50% to 80% 95% confidence interval). The 5-year progression-free survival estimate is 53%, and the 5-year survival estimate is 80%. There were no deaths, 2 patients had grade 4 toxicity, 14 grade 3 toxicity, 17 grade 2 toxicity, 6 grade 1 toxicity, and only 3 had no toxicity reported as their worst toxicity grade. CONCLUSIONS: The combination failed to show an estimated response higher than 80%. It is not recommended that further evaluation of this combination be conducted.     

Flexible ureteroscopy for lower calyceal stones in a horseshoe kidney – Is it the new treatment of choice?

IntroductionThe efficacy of retrograde intrarenal surgery (RIRS) for the treatment of disorders in a horseshoe kidney has not been sufficiently studied so far. We report on our experience with this method for the treatment of lower-pole calculi in patients with a horse-shoe kidney.Patients and methodsThe files of 9 patients who underwent RIRS for lower calyceal stones in horseshoe kidneys between April 2012 and December 2014 were retrospectively analyzed. The stone-free status, postoperative complications, operative time and duration of hospitalization were assessed.ResultsIn total, 12 renal units with lower calyceal stones were treated, as 3 patients had stones in both kidneys. In 8 renal units complete stone clearance could be achieved in one sitting (67.7%), while in 3 renal units 2 sittings were necessary in order to achieve stone clearance. One patient with a stone sized 18 mm still had residual stones after two sittings and, therefore, underwent percutaneous nephrolithotomy (PCNL) for stone clearance. No major complications (Clavien–Dindo grades III–V) were encountered.ConclusionRIRS for the treatment of stone disease in horseshoe kidneys has been shown to be a relatively safe and effective procedure. However, due to the anatomical abnormality, a second look may be needed to render the patient completely stone-free.     

Does smoking change the efficacy of combination therapy with vitamin E and colchicines in patients with early-stage Peyronie's disease?

This study was conducted to find out if smoking has an effect on the results of combination therapy with vitamin E and colchicines in patients with early-stage Peyronie's disease (PD). A total of 58 potent patients suffering from early-stage PD were included in the study (mean age 47.3 years, range 25-73 y). The time from onset of the disease was <6 months and no patient had ED. The patients with severe fibrotic or calcified plaques were not included in the study. Of the patients, 36 were smokers (Group 1) and 22 were non-smokers (Group 2). All the patients received vitamin E (800 IU daily) and colchicines (1 mg daily) for 6 months. Follow-up ranged from 5 to 13 months (mean 10.3 m). The combination therapy was effective and well tolerated in both groups. There were no significant differences between the two groups according to age, disease duration, related disease (diabetes, hypertension, hypercholesterolemia, and hypertriglyceridemia), plaque sizes, and plaque numbers. The resolution in pain and increase in penile curvature and plaque size were similar rates in both groups (p > 0.05), while decrease in penile curvature and plaque size were higher in Group 2 (p < 0.05). No patient discounted the therapy due to side effects. The oral combination therapy with vitamin E and colchicines appears to be an effective procedure in patients with early-stage PD and smoking may have worsening effects on the treatment results.     

Effect of intravenous dexamethasone on postoperative pain after spinal anaesthesia – a systematic review with meta-analysis and trial sequential analysis

There are data suggesting that intravenous dexamethasone has an effect on postoperative analgesia when given during single-shot spinal anaesthesia. However, the research literature is equivocal. We performed a systematic literature search followed by conventional meta-analysis (random effects model). We used trial sequential analysis to control for type-1 and -2 statistical errors. We also performed a leave-one-out meta-analysis for our primary outcome, the consumption of intravenous morphine in the first 24 postoperative hours. We applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to rate the level of evidence. We obtained data from 1133 patients, reported in 17 trials. Reporting quality was high, with low risk of bias. Dexamethasone use was associated with a significant reduction in 24-h morphine consumption, the mean difference (95%CI) being −4.01 (−5.01 to −3.01) mg, 6 trials, 326 participants, I² = 0%. Trial sequential analysis showed that there was firm evidence for the primary outcome, and leave-one-out meta-analysis showed that our result was not driven by one single trial. The GRADE evaluation showed a high level of evidence, suggesting that further studies are unlikely to alter the result. The time to first analgesic request (95%CI) was significantly prolonged by 86.62 (10.62–162.62) min, I² = 93%, in the dexamethasone group. For other secondary outcomes including number of patients requiring rescue analgesia, or visual analogue scale pain scores, we found no evidence of a significant difference between the treatment arms. We report a high level of evidence that intravenous dexamethasone improves postoperative analgesia after spinal anaesthesia.