Real-world efficacy and safety of Ledipasvir plus Sofosbuvir and Ombitasvir/Paritaprevir/Ritonavir +/- Dasabuvir combination therapies for chronic hepatitis C: A Turkish experience

Background/Aims: This study aimed to evaluate the real-life efficacy and tolerability of direct-acting antiviral treatments for patients with chronic hepatitis C (CHC) with/without cirrhosis in the Turkish population.Material and Methods: A total of 4,352 patients with CHC from 36 different institutions in Turkey were enrolled. They received ledipasvir (LDV) and sofosbuvir (SOF)+/- ribavirin (RBV) ombitasvir/paritaprevir/ritonavir +/- dasabuvir (PrOD)+/- RBV for 12 or 24 weeks. Sustained virologic response (SVR) rates, factors affecting SVR, safety profile, and hepatocellular cancer (HCC) occurrence were analyzed.Results: SVR12 was achieved in 92.8% of the patients (4,040/4,352) according to intention-to-treat and in 98.3% of the patients (4,040/4,108) according to per-protocol analysis. The SVR12 rates were similar between the treatment regimens (97.2%-100%) and genotypes (95.6%-100%). Patients achieving SVR showed a significant decrease in the mean serum alanine transaminase (ALT) levels (50.90 +/- 54.60 U/L to 17.00 +/- 14.50 U/L) and model for end-stage liver disease (MELD) scores (7.51 +/- 4.54 to 7.32 +/- 3.40) (p<0.05). Of the patients, 2 were diagnosed with HCC during the treatment and 14 were diagnosed with HCC 37.0 +/- 16.0 weeks post-treatment. Higher initial MELD score (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.22-2.38; p=0.023]), higher hepatitis C virus (HCV) RNA levels (OR: 1.44, 95% CI: 1.31-2.28; p=0.038), and higher serum ALT levels (OR: 1.38, 95% CI: 1.21-1.83; p=0.042) were associated with poor SVR12. The most common adverse events were fatigue (12.6%), pruritis (7.3%), increased serum ALT (4.7%) and bilirubin (3.8%) levels, and anemia (3.1%).Conclusion: LDV/SOF or PrOD +/- RBV were effective and tolerable treatments for patients with CHC and with or without advanced liver disease before and after liver transplantation. Although HCV eradication improves the liver function, there is a risk of developing HCC.Turkish Association for the Study of The Liver (TASL

Volume CXIV, Number 4, November 7, 1996

Objective: Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls. This study aimed to systematically investigate the key clinical features of TS in relationship to karyotype in a large pediatric Turkish patient population.Methods: Our retrospective study included 842 karyotype-proven TS patients aged 0-18 years who were evaluated in 35 different centers in Turkey in the years 2013-2014.Results: The most common karyotype was 45,X (50.7%), followed by 45,X/46,XX (10.8%), 46,X,i(Xq) (10.1%) and 45,X/46,X,i(Xq) (9.5%). Mean age at diagnosis was 10.2±4.4 years. The most common presenting complaints were short stature and delayed puberty. Among patients diagnosed before age one year, the ratio of karyotype 45,X was significantly higher than that of other karyotype groups. Cardiac defects (bicuspid aortic valve, coarctation of the aorta and aortic stenosis) were the most common congenital anomalies, occurring in 25% of the TS cases. This was followed by urinary system anomalies (horseshoe kidney, double collector duct system and renal rotation) detected in 16.3%. Hashimoto's thyroiditis was found in 11.1% of patients, gastrointestinal abnormalities in 8.9%, ear nose and throat problems in 22.6%, dermatologic problems in 21.8% and osteoporosis in 15.3%. Learning difficulties and/or psychosocial problems were encountered in 39.1%. Insulin resistance and impaired fasting glucose were detected in 3.4% and 2.2%, respectively. Dyslipidemia prevalence was 11.4%.Conclusion: This comprehensive study systematically evaluated the largest group of karyotype-proven TS girls to date. The karyotype distribution, congenital anomaly and comorbidity profile closely parallel that from other countries and support the need for close medical surveillance of these complex patients throughout their lifespa

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Effects of Tribulus terrestris L. and post-ischemia/reperfusion redox balance in ovaries, kidneys, and brain

Amaç: Oksidatif stres prooksidan ve antioksidan sistemler arasında oksidasyon lehine bir dengesizlik olarak tanımlanır ve iskemi / reperfüzyon hasarı gibi çeşitli patolojilerden sorumlu tutulmaktadır. Eksojen antioksidanlar redoks dengesinin geri kazanılmasında faydalıdırlar. Tribulusterrestris L. (demir dikeni) güçlü antioksidan etki sergileyen flavonoidler ve saponinler açısından zengin bir tıbbi bitkidir. Bu çalışma over, böbrek ve beyinde reperfüzyon hasarında Tribulus ekstresinin redoks dengesi üzerine etkilerini araştırmayı hedeflemiştir. Yöntemler: Dişi Wistar albino sıçanlaraTribulus veya fizyolojik salin uygulandı ve hayvanlar 60 dakika süreli over, böbrek ya da beyin iskemisini takip eden 60 dakika süreli reperfüzyona maruz bırakıldılar. Bahsedilen dokularda total antioksidan durum (TOS), total oksidan durum (TAS) ve oksidatif stres indeksi (OSI) belirlendi. Bulgular: Tribulus’un over, böbrek ve beyinde yalnızca reperfüzyon hasarı oluşturulan hayvanlara kıyasla TOS’u düşürdüğü bulundu (sırasıyla, p<0.001, p=0.004 ve p=0.035). Aynı zamanda Tribulus uygulamasıyla her üç dokuda yalnızca reperfüzyon hasarı oluşturulan hayvanlara kıyasla redoks dengesinin önemli bir göstergesi olan OSI’de azalma sağlandı (over: p<0.001, böbrek: p=0.007 ve beyin: p=0.002). Sonuç: Bu bulgular Tribulus’un reperfüzyon hasarının yüksek oksidatif ortamında dahi güçlü bir antioksidan etki sergilediğini ortaya koymaktadır. Oksidatif stresin reperfüzyon hasarının yıkıcı sürecine iştiraki düşünüldüğünde Tribulus’un stresi sınırlayıcı etkisi, redoks dengesinin korunmasına katkı sunmak marifetiyle reperfüzyon hasarına karşı faydalı olabileceğini göstermektedir.Objective: Oxidative stress is defined as the imbalance in pro-oxidative and anti-oxidative systems in favor of oxidation, and it is held responsible for numerous pathologies including ischemia/reperfusion injury. Exogenous antioxidants are of benefit to the restoration of the redox balance. Tribulusterrestris L. (devil’s weed) is a medicinal herb, rich in flavonoids and saponins that exert strong anti-oxidant actions. The present study was aimed to investigate the effects of Tribulus extract on the redox balance in ovarian, renal and cerebral reperfusion injury. Method: Female Wistar albino rats were either received Tribulus or physiological saline and undergone to ovarian, renal or cerebral ischemia for 60 minutes followed by a 60-minute-long reperfusion. Total anti-oxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) were estimated in the mentioned tissues. Results: Tribulus was found to reduce TOS in ovaries, kidneys and brain as compared with the animals in which only reperfusion injury was generated (respectively, p<0.001, p=0.004 and p=0.035). Meanwhile, a decrease in OSI, a pivotal indicator of the redox balance, was acquired with Tribulus administration in all three tissues compared with the animals in which only reperfusion injury was generated (ovary: p<0.001, kidney: p=0.007 and brain: p=0.002). Conclusion: These findings demonstrate that Tribulus possesses a strong anti-oxidant effect even in highly oxidative environment of reperfusion injury. Since oxidative stress participates in the destructive process in reperfusion injury, the stress-limiting feature of Tribulus can offer a use against the reperfusion injury through supporting maintenance of the redox balance

Anticonvulsive and Behavior Modulating Effects of Sophoretin and Rutoside

Introduction: Seizures are the hallmarks of most types of epilepsies. Behavioral and cognitive impairments coincide with interictal periods even though it is not clear whether these impairments spring out of the seizure itself or accompanying sociopsychological burden of the disease. Materials and methods: In this study, we investigated behavioral and cognitive consequences of a single GABA receptor-related seizure in mice, and examined the potential anticonvulsive and behavior-modulating properties of sophoretin (quercetin) and rutoside (rutin). Results: The study demonstrated that sophoretin and rutoside, common flavonoids of the human diet, delay the seizure onset and reduce the seizure stage. Moreover, they exerted an antidepressant-like effect, which was independent of the seizure. Neither treatments nor seizure altered recognition and spatial memory performances of the mice. Conclusions: Behavioral or cognitive disturbances that are evident in epileptic patients did not appear following a single seizure. In addition, we suggest that both sophoretin and rutoside successfully alleviate the seizure severity without interfering in the behavioral stability and cognitive performance. Hence, these flavonoids may be of use as adjuncts to the current treatment options

Hipotalamik-hipofizer-adrenal aks üzerine sisplatin ve kurkuminin etkileri

Amaç: Son yıllarda zerdeçaldaki aktif polifenol olan kurkumininsisplatin içeren kemoterapi rejimlerinde sinerjistik bir role sahip olduğunu gösteren bilgiler artmaktadır. Kurkuminin güvenli bir adjuvan olduğunu göstermek için söz konusu ajanların sistemik etkileşimlerinin araştırılması gerektiğinden bu polifenolünsisplatin uygulanan sıçanlarda hipotalamik-hipofizer-adrenal (HPA) aksa etkilerinin incelemesi amaçlandı.Gereç ve Yöntem: Toplamda 34 erkek Wistar sıçan kontrol (n7), sisplatin (n10), kurkumin(n7) ve sisplatin kurkumin (n10) olmak üzere dört gruba ayrıldı. Sisplatin ve kurkumin gruplarındaki sıçanlara 5 hafta süresince (sırasıyla) 5 mg/kg/hafta, i.p. sisplatin ve 300 mg/kg/gün, p.o. kurkumin uygulandı. Sisplatin kurkumin grubu aynı dozlarda hem sisplatin hem kurkumin aldı. Kontrol grubuna yalnızca taşıyıcı (fizyolojik salin ve mısır yağı) verildi. Hayvanlar adrenokortikotropik hormon (ACTH) ve kortikosteron (CORT) ölçümleri için kan elde etmek maksadıyla eksanguine edildi. Beyin çıkarıldı ve hipokampal dokuda mineralokortikoid (MR) ve glukokortikoid (GR) reseptörleri belirlendi. Analizler ELISA yöntemiyle gerçekleştirildi.Bulgular: Sisplatin ve kurkumin tedavilerinin araştırılan parametreleri bozmadığını bulduk (p0.05). Ayrıca, kurkumin ve sisplatinin birlikte uygulanmasının kontrollere kıyasla ACTH ve CORT'un plazma konsantrasyonları ile hipokampal MR ve GR seviyelerini değiştirmediğini gözlendi (p0.05).Sonuç: Sonuçlarımıza göre tek başına veya kombine halde sisplatin ve kurkumin tedavisi HPA aksını etkilememektedir.Objective: There are recently growing evidences as to the synergistic role of curcumin, the active polyphenol of turmeric, in cisplatin containing chemotherapy regimens. The effects of this polyphenol on the hypothalamic-pituitary-adrenal (HPA) axis in cisplatin-treated rats were investigated to figure out systemic interactions of the mentioned agents which is necessary in order to ascertain the safety of curcumin as an adjuvant.Material and Methods: A total of 34 male Wistar rats were divided into four groups as control (n7), curcumin (n10), and cisplatin curcumin (n10). Respectively, 5 mg/kg/week, i.p. cisplatin or 300 mg/kg/day, p.o.curcumin was administered for 5 weeks to the rats in cisplatin and curcumin groups. The cisplatin curcumin group received both cisplatin and curcumin in same doses. Only vehicle (physiological saline and corn oil) was given to the control group. The animals were exsanguinated to obtain blood for adrenocorticotropic hormone (ACTH) and corticosterone (CORT) measurements. The brains were excised and hippocampal mineralocorticoid (MR) and glucocorticoid receptors (GR) receptors were estimated. The analyses were conducted by the ELISA method.Results: We found that the cisplatin and curcumin treatments did not alter the investigated parameters (p<0.05). Also, we observed that the co-administration of curcumin and cisplatin did not change the plasma concentrations of ACTH and CORT as well as the levels of hippocampal MR and GR as compared to the controls (p<0.05).Conclusion: To our results, singly or combined cisplatin and curcumin treatments do not influence the HPA axis

Hipotalamik-hipofizer-adrenal aks üzerine sisplatin ve kurkuminin etkileri

Amaç: Son yıllarda zerdeçaldaki aktif polifenol olan kurkumininsisplatin içeren kemoterapi rejimlerinde sinerjistik bir role sahip olduğunu gösteren bilgiler artmaktadır. Kurkuminin güvenli bir adjuvan olduğunu göstermek için söz konusu ajanların sistemik etkileşimlerinin araştırılması gerektiğinden bu polifenolünsisplatin uygulanan sıçanlarda hipotalamik-hipofizer-adrenal (HPA) aksa etkilerinin incelemesi amaçlandı.Gereç ve Yöntem: Toplamda 34 erkek Wistar sıçan kontrol (n=7), sisplatin (n=10), kurkumin(n=7) ve sisplatin + kurkumin (n=10) olmak üzere dört gruba ayrıldı. Sisplatin ve kurkumin gruplarındaki sıçanlara 5 hafta süresince (sırasıyla) 5 mg/kg/hafta, i.p. sisplatin ve 300 mg/kg/gün, p.o. kurkumin uygulandı. Sisplatin + kurkumin grubu aynı dozlarda hem sisplatin hem kurkumin aldı. Kontrol grubuna yalnızca taşıyıcı (fizyolojik salin ve mısır yağı) verildi. Hayvanlar adrenokortikotropik hormon (ACTH) ve kortikosteron (CORT) ölçümleri için kan elde etmek maksadıyla eksanguine edildi. Beyin çıkarıldı ve hipokampal dokuda mineralokortikoid (MR) ve glukokortikoid (GR) reseptörleri belirlendi. Analizler ELISA yöntemiyle gerçekleştirildi.Bulgular: Sisplatin ve kurkumin tedavilerinin araştırılan parametreleri bozmadığını bulduk (p>0.05). Ayrıca, kurkumin ve sisplatinin birlikte uygulanmasının kontrollere kıyasla ACTH ve CORT'un plazma konsantrasyonları ile hipokampal MR ve GR seviyelerini değiştirmediğini gözlendi (p>0.05).Sonuç: Sonuçlarımıza göre tek başına veya kombine halde sisplatin ve kurkumin tedavisi HPA aksını etkilememektedir.Objective: There are recently growing evidences as to the synergistic role of curcumin, the active polyphenol of turmeric, in cisplatin containing chemotherapy regimens. The effects of this polyphenol on the hypothalamic-pituitary-adrenal (HPA) axis in cisplatin-treated rats were investigated to figure out systemic interactions of the mentioned agents which is necessary in order to ascertain the safety of curcumin as an adjuvant.Material and Methods: A total of 34 male Wistar rats were divided into four groups as control (n=7), curcumin (n=10), and cisplatin + curcumin (n=10). Respectively, 5 mg/kg/week, i.p. cisplatin or 300 mg/kg/day, p.o.curcumin was administered for 5 weeks to the rats in cisplatin and curcumin groups. The cisplatin + curcumin group received both cisplatin and curcumin in same doses. Only vehicle (physiological saline and corn oil) was given to the control group. The animals were exsanguinated to obtain blood for adrenocorticotropic hormone (ACTH) and corticosterone (CORT) measurements. The brains were excised and hippocampal mineralocorticoid (MR) and glucocorticoid receptors (GR) receptors were estimated. The analyses were conducted by the ELISA method.Results: We found that the cisplatin and curcumin treatments did not alter the investigated parameters (p&gt;0.05). Also, we observed that the co-administration of curcumin and cisplatin did not change the plasma concentrations of ACTH and CORT as well as the levels of hippocampal MR and GR as compared to the controls (p&gt;0.05).Conclusion: To our results, singly or combined cisplatin and curcumin treatments do not influence the HPA axis