Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma.

BACKGROUND: In the phase III HIMALAYA study (NCT03298451) in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS. Results reported herein are from a 4-year updated OS analysis of HIMALAYA. PATIENTS AND METHODS: Participants with uHCC and no previous systemic treatment were randomized to STRIDE (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The updated data cut-off was 23 January 2023. OS and serious adverse events (AEs) were assessed. Additionally, baseline characteristics and subsequent therapies were analyzed in long-term survivors (≥36 months beyond randomization). RESULTS: For STRIDE, durvalumab, and sorafenib, median [95% confidence interval (CI)] follow-up was 49.12 months (46.95-50.17 months), 48.46 months (46.82-49.81 months), and 47.31 months (45.08-49.15 months), respectively. OS hazard ratio (95% CI) for STRIDE versus sorafenib was 0.78 (0.67-0.92). The 36-month OS rate for STRIDE was 30.7% versus 19.8% for sorafenib. The 48-month OS rate remained higher for STRIDE at 25.2%, versus 15.1% for sorafenib. The long-term OS benefit of STRIDE was observed across clinically relevant subgroups and was further improved in participants who achieved disease control. Long-term survivors with STRIDE (n = 103) included participants across clinically relevant subgroups, and 57.3% (59/103) had no reported subsequent anticancer therapy. No new serious treatment-related AEs occurred with STRIDE from the primary analysis (17.5%; 68/388). Durvalumab maintained OS noninferiority to sorafenib and no late-onset safety signals were identified. CONCLUSIONS: These data represent the longest follow-up to date in phase III studies in uHCC. The unprecedented 3- and 4-year OS rates reinforce the sustained long-term OS benefit of STRIDE versus sorafenib. STRIDE maintained a tolerable yet differentiated safety profile from other current uHCC therapies. Results continue to support the long-term benefits of STRIDE in a diverse population, reflective of uHCC globally.

[MEDICAL TOURISM IN UKRAINE: STATE, PROBLEMS AND PROSPECTS].

Global processes touch on and affect of various spheres and braGlobal processes touch on and affect of various spheres and branches of human activity, including the health sector. «Open¼ borders facilitate the migration of people around the world. One of the goals of such migration is to obtain medical services. According to the World Health Organization, by 2022, the health and tourism sectors will jointly become one of the world's significant industries, which also will be facilitated by the global tendency of «aging¼ of the world's population. In recent years, medical tourism accounts for about 2% of world GDP. Development of the sphere of medical services gives rise to the practical need for the legal consolidation of the institution of medical tourism. Due to the fact that the number of people who want to combine rest and treatment is growing rapidly, this situation leads to the consideration of a fairly new sphere in the healthcare industry as medical tourism. The purpose of the study is to analyse the development of medical tourism in Ukraine, identify its problematic theoretical and practical aspects both in the tourist sphere of Ukraine and in the healthcare sector, as well as to search for scientifically-based ways to improve the regulatory and legal mechanism that regulates the activities of medical tourism in Ukraine. To achieve this goal have been investigated the medico-legal nature of medical tourism in Ukraine, an analysis of its implementation in the field of international medical tourism, the mechanisms of its implementation. In Ukraine, have been created public organizations to develop medical tourism as one of the most promising areas of health care, aimed at interacting with Ukrainian and international public and charitable organizations. At the same time, it should be noted that at the initial stage medical tourism needs both legal regulation and state financial support. It is necessary to highlight the subjects of such activities at the legislative level, paying special attention to medical providers, the mechanism of influence on them by the state, their functional responsibilities, which can be organization and support of the patient during travel, the search for clinics and the conclusion of contracts with them for the provision of medical services, conclusion of contracts for the provision of services for transportation, accommodation, insurance. Attracting investors and government funding will allow the restoration of unique medical resorts, clinics and hospitals in the development of reproductive health, spa and rehabilitation treatment; create more favourable conditions for attracting foreign patients.

Combined treatment for unresectable head and neck tumors using radiotherapy in combination with regional chemotherapy.

This article is concerned with treatment for unresectable epithelial tumors of the head and neck. It gives a detailed account of the experience of radiation therapy in combination with selective regional chemotherapy administration as a method of combined treatment. According to the study result the complete tumor responce was demonstrated in 5.3% cases; participal tumor responce - in 80.4%; stable disease - in10.7%; progression of the tumor proces - in 3.6%. The reported adveres events and their treatment details are described for all severity as per NCI-CTCAE. The performed analysis suggests the preliminary study treatment results and the advantages of the selected scheme.

Acute cholestatic liver injury caused by polyhexamethyleneguanidine hydrochloride admixed to ethyl alcohol.

INTRODUCTION: Polyhexamethyleneguanidine hydrochloride (PHMG) is an antimicrobial biocide of the guanidine family. In the period from August 2006 to May 2007, more than 12500 patients were admitted to hospital with a history of drinking illegal cheap "vodka" in 44 different regions in Russia, of whom 9.4% died. In reality, the "vodka" was an antiseptic liquid composed of ethanol (≈93%), diethyl phthalate, and 0.1-0.14% PHMG (brand name "Extrasept-1"). MATERIAL AND METHODS: We performed an analysis of the clinical features and outcome in four poisoning treatment centers in the cities of Perm, Ekaterinburg, Irkutsk, and Khabarovsk. A total of 579 patients (215 females and 364 males) with similar symptoms were included. RESULTS: The main symptoms on admission included jaundice (99.7%), skin itch (78.4%), weakness (96%), anorexia (65.8%), dizziness (65.3%), nausea (54.8%), vomiting (22.6%), stomach ache (52.7%), diarrhea (32%), and fever (50%). Mild symptoms were found in 2.5% of cases, moderate in 63%, and severe in 34.5%. Laboratory results were (mean ± SD): total bilirubin 249 ± 158 µmol/L, direct bilirubin 166 ± 97 µmol/L, cholesterol 14 ± 8 mmol/L, alanine aminotransferase 207 ± 174 IU/L, aspartate aminotransferase 174 ± 230 IU/L, alkaline phosphatase 742 ± 751 IU/L, and gamma-glutamyltranspeptidase 1199 ± 1095 IU/L. Patients generally recovered over a period of 1-5 months, although high levels of alkaline phosphatase and gamma-glutamyltranspeptidase were still found in all patients examined after 6 months. Sixty-one patients (10.5%) died between 23 and 150 days after poisoning. Local cholestasis, inflammatory infiltration, and fibrosis developing into cirrhosis were found by liver biopsy. CONCLUSION: Acute liver injury caused by PHMG-hydrochloride or PHMG in combination with either ethanol or diethyl phthalate can be characterized as cholestatic hepatitis with a severe inflammatory component causing high mortality.

Clinical and institutional aspects of antidote therapy in Russia.

The problem of antidote application for treatment of acute poisoning is related to epidemiology and characterization of poisoning cases, and possibilities for supplying antidotes to health care institutions. To investigate the situation in Russia we have analyzed reports by poisoning treatment centers for 1997-1999, comparison of medical aid standards for poisoning treatment in Russia with WHO recommendations. Acute poisoning pattern varies in different regions. Particularly, poisoning pattern in large cities in European Russia and the Urals is dominated by pharmaceuticals (up to 63.1%). Pesticide and insecticide poisoning cases do not exceed 1 to 2%, metal compounds and methemoglobin forming poisons (below 1% in each group). Antidotes are used in Russia in line with the recommendations adopted in international toxicological practice. The most actual are antagonists of opiates and benzodiazepines, physostigmine, atropine, pyridoxine, antagonists of beta-adrenergic blockers, activated charcoal. Such antidotes as DMPS (Unithiol), N-acetylcysteine, methylene blue, amyl nitrite (or sodium nitrite), complex formers of EDTA group are also included in the list of specific agents. The main problem is that some important antidotes are currently not produced in Russia. The Ministry of Health of the Russian Federation is taking efforts to launch production of some previously known and also newly developed important antidotes.

Epidemiology and medical aid at acute poisoning in Russia.

The present study is based on the selected data obtained from medical reports by some Russian poisoning treatment centers, recent publications, statistical materials, and the review of the existing system of medical aid at acute poisoning. The number of acute poisoning cases in Moscow and large Russian cities has increased almost twofold in the last fifteen years. The main groups of toxic agents causing poisoning are pharmaceuticals (up to 63.1%), alcohol and surrogates (up to 49.3%), corrosives (up to 21.8%), although the figures vary in various Russian regions. Acute poisoning mortality in Russia tends to increase with about 56,000 in the recent years. The main causes of poisoning were alcohol (62.2%), carbon monoxide (15.4%), acetic acid (6.3%), pharmaceuticals (4%) (data by the Moscow Forensic Bureau). Specialized medical aid is represented by poisoning treatment centers organized in 37 cities, 1 toxicology information and advisory center of federal level. Physicians can advance their skills at post-diploma courses organized at 4 chairs of clinical toxicology. Scientific research in the field is carried out by Moscow city poisoning treatment center, the abovementioned chairs and other interested institutions. To obtain the maximum complete data on the number, pattern and causes of acute poisoning a unified system for toxicological monitoring was introduced in Russia in 2000.

Information technologies for clinical toxicology in Russia.

OBJECTIVE: To describe Poison Information in Russia. RESULTS: The Moscow Toxicology Information and Advisory Center was created in 1993 as an institution of the Russian Federation Ministry of Health and Medical Industry. The Toxicology Information and Advisory Center is the first in a network of over 20 toxicology information centers to be created in different regions of Russia by 1998. At present the Toxicology Information and Advisory Center serves over 20 million people in the Moscow region with episodic inquiries from other areas. A prototype national bank of clinical and toxicological data on acute chemical poisoning and an information retrieval system POISON have been created. Work is underway to create computerized systems for data analysis of telephone inquiries on diagnosis and treatment protocols of acute poisoning.