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

State of the climate in 2018

In 2018, the dominant greenhouse gases released into Earth’s atmosphere—carbon dioxide, methane, and nitrous oxide—continued their increase. The annual global average carbon dioxide concentration at Earth’s surface was 407.4 ± 0.1 ppm, the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contribute just over 3 W m−2 to radiative forcing and represent a nearly 43% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. With a weak La Niña in early 2018 transitioning to a weak El Niño by the year’s end, the global surface (land and ocean) temperature was the fourth highest on record, with only 2015 through 2017 being warmer. Several European countries reported record high annual temperatures. There were also more high, and fewer low, temperature extremes than in nearly all of the 68-year extremes record. Madagascar recorded a record daily temperature of 40.5°C in Morondava in March, while South Korea set its record high of 41.0°C in August in Hongcheon. Nawabshah, Pakistan, recorded its highest temperature of 50.2°C, which may be a new daily world record for April. Globally, the annual lower troposphere temperature was third to seventh highest, depending on the dataset analyzed. The lower stratospheric temperature was approximately fifth lowest. The 2018 Arctic land surface temperature was 1.2°C above the 1981–2010 average, tying for third highest in the 118-year record, following 2016 and 2017. June’s Arctic snow cover extent was almost half of what it was 35 years ago. Across Greenland, however, regional summer temperatures were generally below or near average. Additionally, a satellite survey of 47 glaciers in Greenland indicated a net increase in area for the first time since records began in 1999. Increasing permafrost temperatures were reported at most observation sites in the Arctic, with the overall increase of 0.1°–0.2°C between 2017 and 2018 being comparable to the highest rate of warming ever observed in the region. On 17 March, Arctic sea ice extent marked the second smallest annual maximum in the 38-year record, larger than only 2017. The minimum extent in 2018 was reached on 19 September and again on 23 September, tying 2008 and 2010 for the sixth lowest extent on record. The 23 September date tied 1997 as the latest sea ice minimum date on record. First-year ice now dominates the ice cover, comprising 77% of the March 2018 ice pack compared to 55% during the 1980s. Because thinner, younger ice is more vulnerable to melting out in summer, this shift in sea ice age has contributed to the decreasing trend in minimum ice extent. Regionally, Bering Sea ice extent was at record lows for almost the entire 2017/18 ice season. For the Antarctic continent as a whole, 2018 was warmer than average. On the highest points of the Antarctic Plateau, the automatic weather station Relay (74°S) broke or tied six monthly temperature records throughout the year, with August breaking its record by nearly 8°C. However, cool conditions in the western Bellingshausen Sea and Amundsen Sea sector contributed to a low melt season overall for 2017/18. High SSTs contributed to low summer sea ice extent in the Ross and Weddell Seas in 2018, underpinning the second lowest Antarctic summer minimum sea ice extent on record. Despite conducive conditions for its formation, the ozone hole at its maximum extent in September was near the 2000–18 mean, likely due to an ongoing slow decline in stratospheric chlorine monoxide concentration. Across the oceans, globally averaged SST decreased slightly since the record El Niño year of 2016 but was still far above the climatological mean. On average, SST is increasing at a rate of 0.10° ± 0.01°C decade−1 since 1950. The warming appeared largest in the tropical Indian Ocean and smallest in the North Pacific. The deeper ocean continues to warm year after year. For the seventh consecutive year, global annual mean sea level became the highest in the 26-year record, rising to 81 mm above the 1993 average. As anticipated in a warming climate, the hydrological cycle over the ocean is accelerating: dry regions are becoming drier and wet regions rainier. Closer to the equator, 95 named tropical storms were observed during 2018, well above the 1981–2010 average of 82. Eleven tropical cyclones reached Saffir–Simpson scale Category 5 intensity. North Atlantic Major Hurricane Michael’s landfall intensity of 140 kt was the fourth strongest for any continental U.S. hurricane landfall in the 168-year record. Michael caused more than 30 fatalities and $25 billion (U.S. dollars) in damages. In the western North Pacific, Super Typhoon Mangkhut led to 160 fatalities and$6 billion (U.S. dollars) in damages across the Philippines, Hong Kong, Macau, mainland China, Guam, and the Northern Mariana Islands. Tropical Storm Son-Tinh was responsible for 170 fatalities in Vietnam and Laos. Nearly all the islands of Micronesia experienced at least moderate impacts from various tropical cyclones. Across land, many areas around the globe received copious precipitation, notable at different time scales. Rodrigues and Réunion Island near southern Africa each reported their third wettest year on record. In Hawaii, 1262 mm precipitation at Waipā Gardens (Kauai) on 14–15 April set a new U.S. record for 24-h precipitation. In Brazil, the city of Belo Horizonte received nearly 75 mm of rain in just 20 minutes, nearly half its monthly average. Globally, fire activity during 2018 was the lowest since the start of the record in 1997, with a combined burned area of about 500 million hectares. This reinforced the long-term downward trend in fire emissions driven by changes in land use in frequently burning savannas. However, wildfires burned 3.5 million hectares across the United States, well above the 2000–10 average of 2.7 million hectares. Combined, U.S. wildfire damages for the 2017 and 2018 wildfire seasons exceeded $40 billion (U.S. dollars)

Echocardiographic evaluation of associated valve lesions in mitral stenosis

Amaç: Mitral darlığına eşlik eden lezyonların darlığın tanısını ve derecesinin belirlenmesini ve tedavisini güçleştirdiği, aynı zamanda prognozunu olumsuz yönde etkilediği bilinmektedir. Mitral aparatın bir ya da daha fazla komponentini etkileyen patolojilerde mitral kapak prolapsusu da oluşabilmektedir. Çalışmamızda mitral darlığı olan hastalarda diğer kapak hastalıklarının özellikle de kapak prolapsusu sıklığının ve bunun ekokardiyografik bulgularla ilişkisinin araştırılması amaçlanmıştır. Yöntem: Çalışmaya mitral darlığı olan 16- 72 yaşları arasındaki (ortalama 40.9±11.4 yaş) 31 erkek, 170 kadın alındı. Kapak alanı transtorasik ekokardiyografiden planimetrik yöntemle ölçüldü ve hastalar ağır (1.5 cm2) derecede darlık olmak üzere üç ayrı gruba ayrıldı. Bulgular: Mitral yetersizliği 117 (%58.2), aort yetersizliği 84 (%41.8), aort darlığı 18 (%9), kombine aort kapak hastalığı 9 (%4.5), triküspid yetersizliği 62 (%30.8) ve triküspid darlığı ise 6 (%3) hastada saptandı. Mitral ön yaprakta prolapsus 23 (%11.4) hastada tespit edildi, arka yaprakta prolapsusa rastlanmadı. Kapak prolapsusu olan ve olmayan mitral darlıklı hastaların yaş, cinsiyet, ritm, darlığının derecesi, mitral ve aort yetersizliğinin derecesi, ortalama basınç farkı, sol atriyum boyutu, ejeksiyon fraksiyonu ve kapak skoru gibi parametreleri açısından bir fark bulunamadı. Sonuç: Ülkemizde romatizmal mitral darlığına sıklıkla diğer kapak hastalıklarının da eşlik ettiği ve romatizmanın seyri esnasında mitral kapak ve kordalarda oluşan değişiklikler nedeniyle kapak prolapsusunun normal populasyona göre daha sık oranda görüldüğü kanısına varıldı.Objective: When mitral stenosis is associated with other valve lesions, diagnosis, prognosis and the treatment strategies are affected. Mitral valve prolapse may occur in some patological settings that affect mitral apparatus. We investigated the incidence of valve lesions including mitral valve prolapse that accompany mitral stenosis and assessed the relation between echocardiographic measures. Methods: Two hundred and one patients (31 male, 170 female) between 16 and 72 years of age (mean age 40.9±11.4 years) with mitral stenosis were included in the study. Patients were divided into three groups according to the mitral valve area obtained by echocardiography using planimetric method as Group I (MVA 1.5 cm2). Results: Mitral stenosis with mitral regurgitation, aortic regurgitation, aortic stenosis, combined aortic valve disease, tricuspid regurgitaion and tricuspid stenosis were found in 117 (58.2%), 84 (41.8%), 18 (9%), 9 (4.5%) , 62 (30.8%) and 6 (3%) patients, respectively. Twenty- three patients (11.4%) had mitral valve prolapse in only anterior leaflet. Nobody of patients had mitral valve prolapse of posterior mitral valve leaflet. Age, gender, rhythm, degree of stenosis, degree of mitral and aortic regurgitations, mean pressure gradient, left atrial diameter, ejection fraction and valve score did not differ in patients with and without mitral valve prolapse. Conclusion: Our study has shown that valve lesions including mitral valve prolapse frequently accompany mitral stenosis and the incidence of mitral valve prolapse in patients with mitral stenosis is high

Effect of Climate Change on Poppy (Papaver somniferum L.) Production Area

İklim, dünyadaki yaşamın sürmesi ve yaşam formlarının yeryüzüne dağılmasında en önemlietmenlerdendir. Bu da yeryüzünde yetişen doğal ve kültür bitkilerinin dağılışını ve kalitesini etkilemektedir.Günümüzde yapılan birçok çalışma iklimde bir değişimin olduğunu göstermektedir. Bu değişim birçok tarımsalüründe olduğu gibi haşhaş üretiminde de hiç şüphesiz etkili olacaktır. Haşhaş (Papaver somniferum L.)insanlık tarihinde en fazla bilinen, tıbbi ve yağ amaçlı kullanılan önemli bir endüstri bitkisidir. Dünya'da, haşhaşüretimi ve afyon alkaloidi ticareti bakımından söz sahibi olan Türkiye'nin haşhaş üretiminin iklimdeğişikliklerinden gelecekte nasıl etkileneceği bu çalışmada tespit edilmeye çalışılmıştır. Bu amaçla; İklimparametrelerinden sıcaklık ve yağış (1961-2013 döneminden derlenen) verileri kullanılmıştır. Haşhaşın;sıcaklık, yağış ve topografyaya bağlı olarak yetişebileceği muhtemel alanlar gösterilmiştir. Sıcaklık ve yağıştopografya ile modellenmiş; sıcaklık için 7-16C aralığındaki ve yağış için 300-1000 mm aralığındaki bölgelerseçilmiştir. Bu iki katmanın kesişim bölgesi, uzun yıllar iklim parametrelerine göre, haşhaşın yaşam bölgesibelirlenmiştir. Gelecekte meydana gelen değişimlerin belirlenebilmesi için iklim değişikliği modellerindenHadGEM-2ES RCP8.5 senaryosu kullanılmıştır. 2015-2040, 2040-2070 ve 2070-2099 dönemleri için sıcaklıkve yağış projeksiyonları kullanılarak, haşhaş ekim alanlarındaki gelecek için muhtemel değişimlergösterilmiştir. Sonuçta; iklim değişikliğinin gelecekte haşhaşın üretim alanlarında azalışlara neden olacağıve bu çalışmanın ekim alanlarının belirlenmesine katkı sağlayacağı düşünülmektedirThe climate is one of the most important factors for continuation of the life in the world and in thedistribution of life forms on earth. It also affects distribution and quality of natural and cultivated plants that'sgrown in the earth. Numerous studies carried out today shows that there is climate change. No doubt, thischange will be effective in many agricultural products as well as in poppy production. Poppy (Papaversomniferum L.), best known in human history, is an important industrial plants used for medicinal and oil. Inthis study, it is intended to determine effects of climate change in future on Turkey's poppy production thatis influential country on poppy production and opium alkaloids trade in the world. To this end, temperatureand precipitation data of climate parameters are used. Possible areas where poppy can begrown are shown depending on temperature, rainfall and topography. Temperature and precipitation aremodeled with topography; regions are selected for the temperature in range of 7-16C and for precipitationin range of 300-1000 mm. Intersections of two layers, according to the long-term climatological parametersare determined as Poppy's life region. One of climate change models; HadGEM-2ES RCP8.5 scenario wereused to determine changes that may be occurred in the future. Using temperature and precipitationprojections for 2015-2040, 2040-2070 and 2070-2099 periods, possible changes are shown in poppycultivation areas for the future. As a result; it is contemplated that climate change would lead to a decreasein the production of poppy fields in the future and this work will contribute to the determination of thecultivation area

What have we learned from Turkish familial hypercholesterolemia registries (A-HIT1 and A-HIT2)?

Background and aims: Familial hypercholesterolemia (FH) is a common genetic disease of high-level cholesterol leading to premature atherosclerosis. One of the key aspects to overcome FH burden is the generation of largescale reliable data in terms of registries. This manuscript underlines the important results of nation-wide Turkish FH registries (A-HIT1 and A-HIT2)

What have we learned from Turkish familial hypercholesterolemia registries (A-HIT1 and A-HIT2)?

WOS: 000445908000052PubMed ID: 30270069Background and aims: Familial hypercholesterolemia (FH) is a common genetic disease of high-level cholesterol leading to premature atherosclerosis. One of the key aspects to overcome FH burden is the generation of largescale reliable data in terms of registries. This manuscript underlines the important results of nation-wide Turkish FH registries (A-HIT1 and A-HIT2). Methods: A-HIT1 is a survey of homozygous FH patients undergoing low density lipoprotein (LDL) apheresis (LA). A-HIT2 is a registry of adult FH patients (homozygous and heterozygous) admitted to outpatient clinics. Both registries used clinical diagnosis of FH. Results: A-HIT1 evaluated 88 patients (27 +/- 11 years, 41 women) in 19 centers. All patients were receiving regular LA. There was a 7.37 +/- 7.1-year delay between diagnosis and initiation of LA. LDL-cholesterol levels reached the target only in 5 cases. Mean frequency of apheresis sessions was 19 +/- 13 days. None of the centers had a standardized approach for LA. Mean frequency of apheresis sessions was every 19 +/- 13 (7-90) days. Only 2 centers were aware of the target LDL levels. A-HIT2 enrolled 1071 FH patients (53 +/- 8 years, 606 women) from 31 outpatients clinics specialized in cardiology (27), internal medicine (1), and endocrinology (3); 96.4% were heterozygous. 459 patients were on statin treatment. LDL targets were attained in 23 patients (2.1% of the whole population, 5% receiving statin) on treatment. However, 66% of statin-receiving patients were on intense doses of statins. Awareness of FH was 9.5% in the whole patient population. Conclusions: The first nationwide FH registries revealed that FH is still undertreated even in specialized centers in Turkey. Additional effective treatment regiments are urgently needed.Turkish Society of Cardiology; Aegerion; Amyrit; AmgenAmgen; PfizerPfizer; SanofiSanofi-AventisA-HIT1 and 2 registries are sponsored by the Turkish Society of Cardiology that receives funding from a variety of sources (including unrestricted research grants from Aegerion, Amyrit, Amgen, Pfizer, and Sanofi)