A randomized controlled phase II trial of a novel composition of paclitaxel embedded into neutral and cationic lipids targeting tumor endothelial cells in advanced triple-negative breast cancer (TNBC).

BACKGROUND: EndoTAG-1, composed of paclitaxel embedded in liposomal membranes targeting tumor endothelial cells, was evaluated for safety and efficacy in advanced triple-negative breast cancer (TNBC). PATIENTS AND METHODS: One hundred and forty patients were treated with weekly EndoTAG-1 (22 mg/m(2)) plus paclitaxel (70 mg/m(2)), twice weekly EndoTAG-1 (2× 44 mg/m(2)), or weekly paclitaxel (90 mg/m(2)) for greater than or equal to four cycles (3-week treatment + 1-week rest) or until progression/toxicity. Primary end point was progression-free survival (PFS) rate evaluated centrally after four cycles of therapy (week 16). The study was not powered for intergroup comparisons. RESULTS: The PFS rate at week 16 was 59.1% [one-sided 95% CI: 45.6, ∞] on combination treatment, 34.2% [21.6, ∞] on EndoTAG-1, and 48.0% [30.5, ∞] on paclitaxel. Median PFS reached 4.2, 3.4, and 3.7 months, respectively. After complete treatment (week 41 analysis), median overall survival (OS) was 13.0, 11.9, and 13.1 months for the modified Intention-to-Treat (ITT) population and 15.1, 12.5, and 8.9 months for the per-protocol population, respectively. The clinical benefit rate was 53%, 31%, and 36% for the treatment groups. Safety analysis revealed known toxicities of the drugs with slight increases of grade 3/4 neutropenia on combination therapy. CONCLUSION: Treatment of advanced TNBC with a combination of EndoTAG-1 and standard paclitaxel [Taxol® (Bristol-Myers Squibb GmbH), or equivalent generic formulation] was well tolerated and showed antitumor efficacy. The positive trend needs to be confirmed in a randomized phase III trial. STUDY REGISTRATION: European Clinical Trials Database: EudraCT number 2006-002221-23. ClinicalTrials.gov identifier: NCT00448305.

Regulatory Resources and Emotional States in Overcoming Difficulties of Self-organization During Lockdown.

The research aimed to study the characteristics of the joint influence of conscious self-regulation and emotional states on life self-organization during a lockdown and identify the factors that contribute to overcoming emerging difficulties. It was conducted online, using the block site builder Tilda Publishing (tilda.ws) and a Google Forms survey administration application. The empirical structural model of regulatory and emotional predictors of self-organization during the lockdown shows that conscious self-regulation in conditions of imposed self-isolation acts as a universal resource for successful self-organization, managing the difficulties of reorganizing one's life, and coping with the anxiety of uncertainty. Positive and negative emotional states affect these processes differently. Optimism significantly contributes to conscious self-regulation, indirectly supporting successful self-organization of life and preventing the development of accomplishments. We identified the regulatory factor ("Cito-resource of self-regulation"), which plays a crucial role in overcoming self-organization difficulties during a lockdown. This factor is represented by the regulatory indicators of modeling significant conditions for achieving goals and reliability. The higher its development, the easier it is for a person to manage the difficulties of self-organization and cope with anxiety caused by uncertainty. Conscious self-regulation acts as a resource for the self-organization of human life in the lockdown conditions, providing a flexible adjustment of behavior to new challenges. High self-regulation and successful self-organization, acting as a resource of stress protection, increases the ability to maintain health. An optimistic attitude, in its turn, positively affects the conscious self-regulation of human activity.

Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study.

BACKGROUND: This phase II study evaluated the safety and activity of ipilimumab, a fully human mAb that blocks cytotoxic T-lymphocyte antigen-4, in patients with advanced melanoma. PATIENTS AND METHODS: Patients with previously treated, unresectable stage III/stage IV melanoma received 10 mg/kg ipilimumab every 3 weeks for four cycles (induction) followed by maintenance therapy every 3 months. The primary end point was best overall response rate (BORR) using modified World Health Organization (WHO) criteria. We also carried out an exploratory analysis of proposed immune-related response criteria (irRC). RESULTS: BORR was 5.8% with a disease control rate (DCR) of 27% (N = 155). One- and 2-year survival rates (95% confidence interval) were 47.2% (39.5% to 55.1%) and 32.8% (25.4% to 40.5%), respectively, with a median overall survival of 10.2 months (7.6-16.3). Of 43 patients with disease progression by modified WHO criteria, 12 had disease control by irRC (8% of all treated patients), resulting in a total DCR of 35%. Adverse events (AEs) were largely immune related, occurring mainly in the skin and gastrointestinal tract, with 19% grade 3 and 3.2% grade 4. Immune-related AEs were manageable and generally reversible with corticosteroids. CONCLUSION: Ipilimumab demonstrated clinical activity with encouraging long-term survival in a previously treated advanced melanoma population.

[Clinical significance of the activity of nitric oxide synthase in patients with leptospirosis].

Endotoxin-induced activation of inducible nitric oxide (NO) synthase (iNOS) becomes one of the triggers of the systemic response syndrome (SIRS). Determination of the activity of iNOS reflects the level of NO accumulation and may serve as a prognostically significant test of the severity of a pathological process. A procedure for determining the monocytic activity of iNOS has been developed on the basis of a histochemical reaction to NADPH-diaphorase. iNOS activity was determined in a group of healthy individuals and in 17 patients with leptospirosis. iNOS activity was decreased or absent (mean 0.56 +/- 0.085 c.u.) in patients with a very severe course of the disease and in those with protracted early convalescence. The increased activity of iNOS during early convalescence testifies to the incompleteness of an infectious process.

[Serum nitric oxide as an additional criterion for evaluating the course of leptospirosis].

The blood level of nitric oxide (NO) was studied during an infectious process in 107 patients with leptospirosis. The content of NO was estimated from the level of the final stable nitrogen cycle metabolite--nitrite was estimated by the Griss reaction. Infectious toxic shock (57%), disseminated intravascular coagulation syndrome (31%), respiratory distress syndrome (36%), and acute renal and hepatic failure (76%) were observed in the examinees. A combination of 3-4 of the above abnormalities was noted in 49% of the patients. There were elevated blood nitrite levels at the onset of the disease in patients with leptospirosis with signs of infectious toxic shock (15.3+/-2.79 micromol/l). In patients with a poor or complicated rehabilitative period, the high levels of nitrite were retained or its concentration repeatedly increased at weeks 3-4 of the disease. It has been shown that the measurements of blood nitrite levels may be used as an additional diagnostic criterion for evaluating the course of leptospirosis.

[Relaparotomy in the surgical treatment of early acute postoperative ileus]. / Primenenie relaparotomii v khirurgicheskom lechenii ostroi rannei posleoperatsionnoi neprokhodimosti kishechnika.

The experience of 71,588 patients surgical treatment was summarized, of whon in 1049 (1.47%) the relaparotomy conduction necessity have occurred, and in 411 (0.57%)--in connection with acute early postoperative ileus (AEPOI) development. The timely diagnosis of developing AEPOI, adequate conduction of reoperation, expedient conduction of intensive therapy permitted to reduce the post-operative mortality for last 5 years from 29.4 to 14.3%.

[Acute early postoperative intestinal obstruction in patients with gastroduodenal ulcer]. / Ostraia ranniaia posleoperatsionnaia neprokhodimost' kishechnika u bol'nykh s gastroduodenal'noi iazvoi.

Results of surgical treatment of 4389 patients with gastroduodenal ulcer were analysed. Relaparotomy (RL) was performed in 215(4.9%) of patients for postoperative complications occurred, including 78(36.3%)--for an acute early postoperative ileus (AEPI). RL was performed in 44.3% of patients after perforated gastroduodenal ulcer suturing in 34.3%--after gastric resection, in 28.8%--after organ preserving operations. Main measures providing the effectiveness of surgical aid rendering to the AEPI patients are an early diagnosis and timely RL performance.

A randomized, double-blind, placebo-controlled, dose ranging study to assess the efficacy and safety of eltrombopag in patients receiving carboplatin/paclitaxel for advanced solid tumors.

OBJECTIVES: Eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist, has been shown to increase platelet counts in adults with chronic immune thrombocytopenia and chronic hepatitis C. This multicenter phase 2 study assessed the efficacy and safety of eltrombopag in patients receiving first-line carboplatin/paclitaxel for the treatment of advanced solid tumors. RESEARCH DESIGN AND METHODS: Patients (N = 183) were randomized to placebo or eltrombopag 50 mg, 75 mg, or 100 mg given orally following chemotherapy on days 2 through 11 of each 21-day cycle, for at least two cycles. The primary endpoint was the difference in platelet count from day 1 in cycle 2 to the platelet nadir in cycle 2. CLINICAL TRIAL REGISTRY NUMBER: NCT00102726. RESULTS: Although the primary endpoint was not met, postnadir platelet counts increased during cycles 1 and 2 in all eltrombopag treatment groups compared with placebo. The most commonly reported adverse events across all study arms (including placebo) were nausea and alopecia and eltrombopag was generally well tolerated. CONCLUSIONS: This study provides preliminary information that eltrombopag does increase platelets in patients receiving chemotherapy for advanced solid tumors. Further investigation is needed to identify the optimal dose(s) and schedule of eltrombopag in patients receiving myelosuppressive chemotherapy.

[The immediate results of treating patients with acute early postoperative intestinal obstruction]. / Blizhaishie rezul'taty lecheniia bol'nykh s ostroi rannei posleoperatsionnoi neprokhodimost'iu kishechnika.

We performed 58,938 operations on the abdominal organs. Three hundred and six (37.8%) patients developed early postoperative acute ileus. After its operative elimination, 22 (7.2%) patients required performance of a reoperation. Ninety (29.4%) patients died. Of them in 72, death was caused by peritonitis, in 18--pneumonia, acute cardiovascular failure, impairement in cerebral circulation and pulmonary thromboembolism.