Apalutamide for patients with metastatic castrationsensitive prostate cancer in East Asia: a subgroup analysis of the TITAN trial / 亚洲男科学杂志(英文版)

Ethnicity might be associated with treatment outcomes in advanced prostate cancer. This study aimed to evaluate the efficacy and safety of androgen deprivation therapy (ADT) combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer (mCSPC). The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial was conducted at 260 sites in 23 countries. This subgroup analysis included patients enrolled in 62 participating centers in China, Japan, and Korea. Radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and PSA changes from baseline were compared between groups in the East Asian population. The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups, respectively. The 24-month radiographic PFS rates were 76.1% and 52.3% in the apalutamide and placebo groups, respectively (apalutamide vs placebo: hazard ratio [HR] = 0.506; 95% confidence interval [CI], 0.302-0.849; P = 0.009). Median time to PSA progression was more favorable with apalutamide than placebo (HR = 0.210; 95% CI, 0.124-0.357; P < 0.001). Median maximum percentages of PSA decline from baseline were 99.0% and 73.9% in the apalutamide and placebo groups, respectively. The most common adverse event (AE) was rash in the apalutamide group, with a higher rate than that in the placebo group (37.3% vs 9.1%). The most common grade 3 or 4 AEs were rash (12 [10.9%]) and hypertension (12 [10.9%]) for apalutamide. The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.

Characteristics of Klebsiella pneumoniae Isolates from Stool Samples of Patients with Liver Abscess Caused by Hypervirulent K. pneumoniae

Inhibitory Effect of Rosae Multiflorae Fructus Extracts on the Receptor Activator of NF-κB Ligand-Induced Osteoclastogenesis through Modulation of P38- and Ca2⁺-Mediated Nuclear Factor of Activated T-Cells Cytoplasmic 1 Expression

BACKGROUND: Rosae Multiflorae fructus (RMF), known to have anti-inflammatory and antioxidant properties, has been used as a traditional remedy for inflammatory diseases such as arthritis in Eastern Asia. However, its effect on osteoclasts, which play a crucial role in resorptive inflammatory bone diseases, is yet to be elucidated.METHODS: The effect of extract of RMF (RMF-E) on receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclastogenesis was examined by tartrate-resistant acid phosphatase (TRAP) staining, real-time polymerase chain reaction and western blot analysis. In addition, RANKL-induced Ca2⁺-oscillation was also investigated.RESULTS: RMF-E remarkably inhibited TRAP+-osteoclast and resorptive pit formation in a dose-dependent manner. In addition, the expression of c-Fos and nuclear factor of activated T-cells cytoplasmic, known as pivotal transcription factors for osteoclast formation in vitro and in vivo, and that of the osteoclast differentiation markers such as Acp5, Oscar, CtsK, Atp6v0d2, Tm7sf4, and Nfatc1 were significantly decreased by RMF-E treatment during osteoclastogenesis. The inhibitory effect of RMF-E on RANKL-induced osteoclastogenesis was caused by the suppression of p38 mitogen-activated protein kinase activation, and RANKL-induced Ca2⁺-oscillation removal via inactivation of Bruton's tyrosine kinase (BTK), and subsequently phospholipase C-γ2.CONCLUSIONS: RMF-E negatively regulates osteoclast differentiation and formation. These findings suggest the possibility of RMF-E as a traditional therapeutic agent against osteoclast-related bone disorders such as osteoporosis, rheumatoid arthritis, and periodontitis.

Type 2 Autoimmune Pancreatitis (Idiopathic Duct-Centric Pancreatitis) Highlighting Patients Presenting as Clinical Acute Pancreatitis: A Single-Center Experience

BACKGROUND/AIMS: Type 2 autoimmune pancreatitis (AIP) has been considered extremely rare in East Asia. This study aimed to clarify the prevalence, clinical characteristics and radiological findings of type 2 AIP highlighting patients presenting as acute pancreatitis in a single center. METHODS: Type 2 AIP patients were classified according to International Consensus Diagnostic Criteria. Radiological findings were compared between type 2 AIP presenting as acute pancreatitis and gallstone pancreatitis. RESULTS: Among 244 patients with AIP, 27 (11.1%) had type 2 AIP (definite, 15 [55.5%] and probable 12 [44.5%]). The median age of patients with type 2 AIP was 29 years (interquartile range, 20 to 39 years). Acute pancreatitis was the most common initial presentation (n=17, 63%) while obstructive jaundice was present in only one patient. Ulcerative colitis (UC) was associated with type 2 AIP in 44.4% (12/27) of patients. Radiological pancreatic imaging such as delayed enhancement of diffusely enlarged pancreas, homogeneous enhancement of focal enlargement/mass, absent/minimal peripancreatic fat infiltration or fluid collection, and multifocal main pancreatic duct narrowings were helpful for differentiating type 2 AIP from gallstone pancreatitis. During follow-up (median, 32.3 months), two patients (2/25, 8%) experienced relapse. CONCLUSIONS: In South Korea, type 2 AIP is not as rare as previously thought. Overall, the clinical profile of type 2 AIP was similar to that of Western countries. Type 2 AIP should be considered in young UC patients with acute pancreatitis of uncertain etiology.

Genome-Wide Association of Genetic Variation in the PSCA Gene with Gastric Cancer Susceptibility in a Korean Population / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Half of the world's gastric cancer cases and the highest gastric cancer mortality rates are observed in Eastern Asia. Although several genome-wide association studies (GWASs) have revealed susceptibility genes associated with gastric cancer, no GWASs have been conducted in the Korean population, which has the highest incidence of gastric cancer. MATERIALS AND METHODS: We performed genome scanning of 450 gastric cancer cases and 1,134 controls via Affymetrix Axiom Exome 319 arrays, followed by replication of 803 gastric cancer cases and 3,693 healthy controls. RESULTS: We showed that the rs2976394 in the prostate stem cell antigen (PSCA) gene is a gastriccancer-susceptibility gene in a Korean population, with genome-wide significance and an odds ratio (OR) of 0.70 (95% confidence interval [CI], 0.64 to 0.77). A strong linkage disequilibrium with rs2294008 was also found, indicating an association with susceptibility. Individuals with the CC genotype of the PSCA gene showed an approximately 2-fold lower risk of gastric cancer compared to those with the TT genotype (OR, 0.47; 95% CI, 0.39 to 0.57). The effect of the PSCA gene on gastric cancer was more prominent in the female population and for diffuse type gastric cancer. CONCLUSION: Our result confirmed that the PSCA gene may be the most important susceptibility gene for gastric cancer risk in a Korean population.

Protective effect of Cordyceps militaris against hydrogen peroxide-induced oxidative stress in vitro

BACKGROUND/OBJECTIVES: Excessive production of reactive oxygen species (ROS) such as hydroxyl (·OH), nitric oxide (NO), and hydrogen peroxide (H2O2) is reported to induce oxidative stress. ROS generated by oxidative stress can potentially damage glial cells in the nervous system. Cordyceps militaris (CM), a kind of natural herb widely found in East Asia. In this study, we investigated the free radical scavenging activity of the CM extract and its neuroprotective effects in H2O2-induced C6 glial cells. MATERIALS/METHODS: The ethanol extract of CM (100–1,000 µg/mL) was used to measure DPPH, ·OH, and NO radical scavenging activities. In addition, hydrogen peroxide (H2O2)-induced C6 glial cells were treated with CM at 0.5–2.5 µg/mL for measurement of cell viability, ROS production, and protein expression resulting from oxidative stress. RESULTS: The CM extract showed high scavenging activities against DPPH, ·OH, and NO radicals at concentration of 1,000 µg/mL. Treatment of CM with H2O2-induced oxidative stress in C6 glial cells significantly increased cell viability, and decreased ROS production. Cyclooxygenase-2 and inducible nitric oxide synthase protein expression was down-regulated in CM-treated groups. In addition, the protein expression level of phospho-p38 mitogen-activated protein kinase (p-p38 MAPK), phospho-c-Jun N-terminal kinase (p-JNK), and phospho-extracellular regulated protein kinases (p-ERK) in H2O2-induced C6 glial cells was down-regulated upon CM administration. CONCLUSION: CM exhibited radical scavenging activity and protective effect against H2O2 as indicated by the increased cell viability, decreased ROS production, down-regulation of inflammation-related proteins as well as p-p38, p-JNK, and p-ERK protein levels. Therefore, we suggest that CM could play the protective role from oxidative stress in glial cells.

Two New Species of the Genus Candelariella from China and Korea

Candelariella is a widespread lineage of lichenized ascomycetes with ambiguous relationships among species that have not solved completely. In this study, several specimens belonging to Candelariella were collected from China and South Korea, and the internal transcribed spacer region was generated to confirm the system position of the newly collected specimens. Combined with a morphological examination and phylogenetic analysis, two new areolate species, Candelariella rubrisoli and C. subsquamulosa, are new to science. Detail descriptions of each new species are presented. In addition, C. canadensis is firstly reported from China mainland.

First detection of a G1-like H9N2 virus in Russia, 2018 / 대한수의학회지

Worldwide, avian influenza H9N2 viruses of different lineages are the most widespread viruses in poultry. However, to date, cases in Russia have not been documented. In this study, we report the first detection of a G1-like H9N2 virus from poultry sampled at live-bird markets in Russia (Far East region) during the winter of 2018 (isolate A/chicken/Amur_Russia/17/2018). We assume there has been further circulation of the A/chicken/Amur_Russia/17/2018 H9N2 virus in the Russian Far East with possible distribution to other regions or countries in 2018–2019.

Benefits and risks of therapeutic alternatives for macrolide resistant Mycoplasma pneumoniae pneumonia in children / 소아과

Although Mycoplasma pneumoniae pneumonia (MPP) has been generally susceptible to macrolides, the emergence of macrolide-resistant MPP (MRMP) has made its treatment challenging. MRMP rapidly spread after the 2000s, especially in East Asia. MRMP is more common in children and adolescents than in adults, which is likely related to the frequent use of macrolides for treating M. pneumoniae infections in children. MRMP is unlikely to be related to clinical, laboratory, or radiological severity, although it likely prolongs the persistence of symptoms and the length of hospital stay. Thereby, it causes an increased burden of the disease and poor quality of life for the patient as well as a societal socioeconomic burden. To date, the only alternative treatments for MRMP are secondary antimicrobials such as tetracyclines (TCs) or fluoroquinolones (FQs) or systemic corticosteroids; however, the former are contraindicated in children because of concerns about potential adverse events (i.e., tooth discoloration or tendinopathy). A few guidelines recommended TCs or FQs as the second-line drug of choice for treating MRMP. However, there have been no evidence-based guidelines. Furthermore, safety issues have not yet been resolved. Therefore, this article aimed to review the benefits and risks of therapeutic alternatives for treating MRMP in children and review the recommendations of international or regional guidelines and specific considerations for their practical application.

Text and Practice in East Asian Medicine: The Structure of East Asian Medical Knowledge Examined by Donguibogam Currents in Contemporary South Korea / 의사학

How do classical texts, such as Hwangdi Neijing and Shanghanlun, continuously play significant roles in medical practices in the history of East Asian medicine? Although this is a significant question in interpreting the position of written texts in the medical history and even for understanding the structure of East Asian medical knowledge, it has been conspicuously underexamined in the studies of East Asian medicine. In order to explore this underrepresented question, this study focuses on currents of tradition in contemporary South Korea. Drawing on anthropological fieldwork at three Donguibogam (Treasured Mirror of Eastern Medicine) currents, it delves into the interaction of text and practice in East Asian medicine. Even though all three currents (Hyun-dong, Byeong-in, Hyung-sang) are based on Donguibogam, their ways of reading the text and organizing clinical practices are diverse. Each current sets up a keyword, such as pulse diagnosis, cause of disease, and appearance-image, and attempts to penetrate the entire Donguibogam through the keyword. This means that the classical medical text is open to plural approaches. This study found that there is a visible gap between a medical text and the reader of the text in East Asia. Masters and currents of tradition are the actors who fill up the gap, continuously interpreting and reinterpreting classical texts, and guiding medical practices of new readers. Adding the history of practice to the body of literature that have focused on the history of written texts, this study will contribute to the history of East Asian medicine.

An Exploration into Life, Body, Materials, Culture of Mediaeval East Asia: Focusing on Emergency Medicine Recipes in Local Medicinals of Koryŏ Dynasty / 의사학

The Emergency Medicine Recipes in Local Medicinals (鄕藥救急方, Hyang'yak Kugŭpbang) (c. 14th century) is known to be one of the oldest Korean medical textbooks that exists in its entirety. This study challenges conventional perceptions that have interpreted this text by using modern concepts, and it seeks to position the medical activities of the late Koryŏ Dynasty 高麗 (918–1392) to the early Chosŏn Dynasty 朝鮮 (1392–1910) in medical history with a focus on this text. According to existing studies, Emergency Medicine Recipes in Local Medicinals is a strategic compromise of the Korean elite in response to the influx of Chinese medical texts and thus a medical text from a “periphery” of the Sinitic world. Other studies have evaluated this text as a medieval publication demonstrating stages of transition to systematic and rational medicine and, as such, a formulary book 方書 that includes primitive elements. By examining past medicine practices through “modern” concepts based on a dichotomous framework of analysis — i.e., modernity vs. tradition, center vs. periphery, science vs. culture — such conventional perceptions have relegated Emergency Medicine Recipes in Local Medicinals to the position of a transitional medieval publication meaningful only for research on hyangchal 鄕札 (Chinese character-based writing system used to record Korean during the Silla Dynasty 新羅 [57 BC–935 AD] to the Koryŏ Dynasty). It is necessary to overcome this dichotomous framework in order to understand the characteristics of East Asian medicine. As such, this study first defines “medicine 醫”, an object of research on medical history, as a “special form of problem-solving activities” and seeks to highlight the problematics and independent medical activities of the relevant actors. Through this strategy (i.e., texts as solutions to problems), this study analyzes Emergency Medicine Recipes in Local Medicinals to determine its characteristics and significance. Ultimately, this study argues that Emergency Medicine Recipes in Local Medicinals was a problem-solving method for the scholar-gentry 士人層 from the late Koryŏ Dynasty to the early Chosŏn Dynasty, who had adopted a new cultural identity, to perform certain roles on the level of medical governance and constitute medical praxis that reflected views of both the body and materials and an orientation distinguished from those of the so-called medicine of Confucian physicians 儒醫, which was the mainstream medicine of the center. Intertwined at the cultural basis of the treatments and medical recipes included in Emergency Medicine Recipes in Local Medicinals were aspects such as correlative thinking, ecological circulation of life force, transformation of materiality through contact, appropriation of analogies, and reasoning of sympathy. Because “local medicinals 鄕藥” is understood in Emergency Medicine Recipes in Local Medicinals as referring to objects easily available from one's surroundings, it signifies locality referring to the ease of acquisition in local areas rather than to the identity of the state of Koryŏ or Chosŏn. As for characteristics revealed by this text's methods of implementing medicine, Korean medicine in terms of this text consisted largely of single-ingredient formulas using diverse medicinal ingredients easily obtainable from one's surroundings rather than making use of general drugs as represented by materia medica 本草 or of multiple-ingredient formulas. In addition, accessible tools, full awareness of the procedures and processes of the guidelines, procedural rituals, and acts of emergency treatment (first aid) were more important than the study of the medical classics, moral cultivation, and coherent explanations emphasized in categorical medical texts. Though Emergency Medicine Recipes in Local Medicinals can be seen as an origin of the tradition of emergency medicine in Korea, it differs from medical texts that followed which specializing in emergency medicine to the extent that it places toxicosis 中毒 before the six climatic factors 六氣 in its classification of diseases.

Genetic Polymorphism of Y Chromosome Haplogroup D-M174 in East Asian Populations / 法医学杂志

Objective To explore the genetic polymorphism of Y chromosome D-M174 haplogroup and sub-haplogroups in East Asia. Methods The samples of 1 426 unrelated male individuals from East Asia were collected, and then 7 Y chromosome haplogroup D-M174 and the Y-SNP of its sub-haplogroups were detected with mini-sequencing. The 22 Y-STR genotypes were detected with DNA Typer™ Y26 kit. The haplogroup was analyzed using direct counting method, heatmap, phylogenetic cluster and network graph cluster, and then distribution of genetic polymorphism and the clustering relation between populations and samples of Y chromosome D haplogroup were discussed. Results Haplogroup D-M174 were distributed mostly among Tibetans （40.96%）and Japanese （35.71%）, while less or none were distributed among the surrounding areas of Tibet and other areas. Conclusion The geographical distribution of Y chromosome D-M174 haplogroup in East Asian populations has significant characteristics.

Risk of Water and Food-Borne Communicable Diseases in Travelers Entering Korea

OBJECTIVES: It was supposed to analyze status and affecting factors in water and food-borne communicable disease by screening entrants with diarrhea symptom at the point of entry in Korea METHODS: Symptomatic travelers with water and food-borne communicable diseases who entered Korea were diagnosed by a health declaration and detection of causative agents in water and food using laboratory tests. Among those entered in 2017, the affecting factors in the incidence of communicable diseases among those who had diarrhea at the entry into Korea, were analyzed, with frequency and chi-square test. RESULTS: The number of travel entrants with gastrointestinal communicable diseases increased by 40.19% from 2013 to 2017. The percentage of causative agents of water and food-borne communicable diseases was the highest at 69.2% from July to September. The rate of detection of causative agents of communicable disease pathogens in travelers from Southeast Asia entering Korea was 70.2%, which was higher than people arriving from East Asia and Central Asia (57.5%; p < 0.001). CONCLUSION: The positive ratio of causative agents of water and food-borne communicable diseases was high among travelers that had entered Korea from July to September, with a high number among entrants from Southeast Asia. Based on the positive detection of causative agents, the entry period and countries visited were statistically significant affecting factors (p < 0.001).

Epidemiology of severe fever and thrombocytopenia syndrome virus infection and the need for therapeutics for the prevention

Over the past ten years there has been a marked increase in cases of severe fever and thrombocytopenia syndrome in East Asia. This tick-borne hemorrhagic fever presents along with clinical signs including high fever and leukopenia. In addition to humans, the virus has also been detected with shared genetic homology in farm animals including goats, cattle, horses, and pigs. Furthermore, several genotypes of severe fever and thrombocytopenia syndrome virus (SFTSV) are currently co-circulating between humans and animals. In China, where the virus was first detected in rural areas in 2009, the SFTSV mortality rate has been reported to be as 6% and higher than 30%, especially in immuno-compromised patients. Moreover, this virus has been isolated in neighbor countries including Japan and South Korea where the fatality rates in 2015 were more than 30% in both countries. In this review, we comprehensively summarize the virology, genotypes, pathogenesis, and epidemiology of SFTSV infection in humans and animals. Currently, a collaborative global approach against SFTSV infection is being undertaken; however, the need for continuous disease surveillance and production of an effective vaccine is imperative as this virus may lead to an epidemic of irreversible status in both humans and animals.

The Efficacy and Underlying Mechanism of Moxibustion in Preventing Cognitive Impairment: A Systematic Review of Animal Studies

Cognitive impairment is age-related and manageable only with early diagnosis and prevention. Moxibustion is widely accepted in East Asia as useful for preventing cognitive impairment. This systematic review of animal studies was conducted to verify the efficacy of moxibustion in preventing cognitive impairment and to elucidate the underlying mechanism. Randomized controlled animal trials that established the efficacy of moxibustion in preventing cognitive impairment were included in the analysis. Results of behavioral tests and the signaling pathways elucidated were extracted and a meta-analysis was conducted with the behavioral test results. The risk of bias was evaluated using 9 items, and reporting quality was evaluated using the ARRIVE (Animal Research: Reporting In Vivo Experiments) Guidelines Checklist. Ten trials involving 410 animals met the inclusion criteria. All studies reported the benefit of moxibustion in preventing cognitive deficits caused by Alzheimer's disease (AD). Among five studies using the Morris water maze test, a significant effect of moxibustion in decreasing the escape time was reported in three studies, increasing the crossing times in four studies, and prolonging the dwelling time in two studies. The effects of moxibustion were demonstrated to be mediated by an increase in the activity of neurotrophins and heat shock protein, modulation of the cell cycle, and suppression of apoptosis and inflammation. However, considering the small number of included studies, the lack of studies investigating entire signaling pathways, and a high risk of bias and low reporting quality, our results need to be confirmed through more detailed studies.

Acute Heart Failure Management

Acute heart failure (AHF) is a life-threatening medical condition, where urgent diagnostic and treatment methods are of key importance. However, there are few evidence-based treatment methods. Interestingly, despite relatively similar ways of management of AHF throughout the globe, mid-term outcome in East Asia, including South Korea is more favorable than in Europe. Yet, most of the treatment methods are symptomatic. The cornerstone of AHF management is identifying precipitating factors and specific phenotype. Multidisciplinary approach is important in AHF, which can be caused or aggravated by both cardiac and non-cardiac causes. The main pathophysiological mechanism in AHF is congestion, both systemic and inside the organs (lung, kidney, or liver). Cardiac output is often preserved in AHF except in a few cases of advanced heart failure. This paper provides guidance on AHF management in a time-based approach. Treatment strategies, criteria for triage, admission to hospital and discharge are described.

New Record of Thapariella anastomusa (Trematoda: Thapariellidae) Metacercariae in Northern Thailand

The family Thapariellidae has been reported in only 3 countries since 1990. The objective of this study was to identify Thapariella anastomusa metacercariae in snails in Thailand based on morphological traits using a light (LM) and a scanning electron microscope (SEM). A total of 94 Filopaludina snails were collected and identified as 50 F. martensi martensi and 44 F. doliaris. Metacercariae of T. anastomusa were recovered from the snails by the crushing method. The overall prevalence was 22.3% (21/94), and the mean intensity was 17.0 per snail. The prevalence in F. martensi martensi was 24.0% (12/50) and F. doliaris 20.5% (9/44) with the mean intensity of 18.8 and 14.8 per snail, respectively. SEM revealed traits such as a concave ventral body and well-developed oral and ventral suckers. This study represents the first report of T. anastomusa in South East Asia. While LM and SEM observations provide novel insights into T. anastomusa metacercarial morphology and life history, the trematode’s life cycle remains unclear. To date, there has been no report of T. anastomusa causing infections in humans. However, the snails F. martensi martensi and F. doliaris carrying the infective stages of T. anastomosa are frequently consumed by Thai people. This consumption, particularly uncooked snails, may present a risk of Thapariella infections in humans.

Identification of a thermal stable allergen in yam (Dioscorea opposita) to cause anaphylaxis

Yam (Dioscorea opposita) is commonly consumed in East Asia, but allergic reaction to this plant food is rare. To date, there is no report of anaphylactic reaction after ingestion of cooked yam. We described 3 cases with anaphylaxis after eating boiled yam and 1 present with oral allergy syndrome as well. Basophil activation test in patients showed positive reactivity to boiled yam extract. In immunoblotting, a 30-kDa protein was recognized by all patients' sera and a 17-kDa band was detected by 1 patient. N-terminal amino acid revealed the 30-kDa IgE reacted band was DB3S, dioscorin in Dioscorea tuber. It promoted us that DB3S was a thermal stable oral allergen to trigger anaphylactic reaction and oral allergy syndrome in cooked yam (D. opposita) allergy. Patients with this plant food allergy should avoid both raw and well-cooked yam.

A review of methods to estimate the visibility factor for bias correction in network scale-up studies / 한국역학회지

Network scale-up is an indirect size estimation method, in which participants are questioned on sensitive behaviors of their social network members. Therefore, the visibility of the behavior affects the replies and estimates. Many attempts to estimate visibility have been made. The aims of this study were to review the main methods used to address visibility and to provide a summary of reported visibility factors (VFs) across populations. We systematically searched relevant databases and Google. In total, 15 studies and reports that calculated VFs were found. VF calculation studies have been applied in 9 countries, mostly in East Asia and Eastern Europe. The methods applied were expert opinion, comparison of NSU with another method, the game of contacts, social respect, and the coming-out rate. The VF has been calculated for heavy drug users, people who inject drugs (PWID), female sex workers (FSWs) and their clients, male who have sex with male (MSM), alcohol and methamphetamine users, and those who have experienced extra-/pre-marital sex and abortion. The VF varied from 1.4% in Japan to 52.0% in China for MSM; from 34.0% in Ukraine to 111.0% in China for FSWs; and from 12.0% among Iranian students to 57.0% in Ukraine for PWID. Our review revealed that VF estimates were heterogeneous, and were not available for most settings, in particular the Middle East and North Africa region, except Iran. More concrete methodologies to estimate the VF are required.