Morphological Evaluation and Immunohistochemical Analysis of the Reparative Potential of the Buccal Fat Pad.

Background and Objectives: There are many surgical techniques for oroantral communication treatment, one of which is the buccal fat pad. Of particular interest is the high reparative potential of the buccal fat pad, which may be contributed to by the presence of mesenchymal stem cells. The purpose of this work is to evaluate the reparative potential of BFP cells using morphological and immunohistochemical examination. Materials and Methods: 30 BFP samples were provided by the Clinic of Maxillofacial and Plastic Surgery of the Russian University of Medicine (Moscow, Russia) from 28 patients. Morphological examination of 30 BFP samples was performed at the Institute of Clinical Morphology and Digital Pathology of Sechenov University. Hematoxylin-eosin, Masson trichrome staining and immunohistochemical examination were performed to detect MSCs using primary antibodies CD133, CD44 and CD10. Results: During staining with hematoxylin-eosin and Masson's trichrome, we detected adipocytes of white adipose tissue united into lobules separated by connective tissue layers, a large number of vessels of different calibers, as well as the general capsule of BFP. The thin connective tissue layers contained neurovascular bundles. Statistical processing of the results of the IHC examination of the samples using the Mann-Whitney criterion revealed that the total number of samples in which the expression of CD44, CD10 and CD133 antigens was confirmed was statistically significantly higher than the number of samples where the expression was not detected (p < 0.05). Conclusions: During the morphological study of the BFP samples, we revealed statistically significant signs of MSCs presence (p < 0.05), including in the brown fat tissue, which proves the high reparative potential of this type of tissue and can make the BFP a choice option among other autogenous donor materials when eliminating OAC and other surgical interventions in the maxillofacial region.

Chronic myeloid leukemia diagnosed in pregnancy: management and outcome of 87 patients reported to the European LeukemiaNet international registry.

The management of chronic myeloid leukemia (CML) diagnosed during pregnancy is a rare and challenging situation. We report the treatment and outcome of 87 cases diagnosed in chronic phase from 2001-2022 derived from the largest international observational registry, supported by the European LeukemiaNet (ELN), of 400 pregnancies in 299 CML women. Normal childbirth occurred in 76% without an increased rate of birth abnormalities or life-threatening events, including in patients untreated or treated with interferon-α and/or imatinib in 2nd-3rd trimester. The low birth weight rate of 12% was comparable to that seen in the normal population. Elective and spontaneous abortions occurred in 21% and 3%, respectively. The complete hematologic response rate before labor was 95% with imatinib and 47% with interferon only. No disease progression during pregnancy was observed, 28% of the patients switched their therapy at varying times after delivery. Treatment options balance the efficacy and safety for mother and infant: interferon-α can commence in the 1st trimester and continued throughout in cases of good disease control and tolerability. Because of limited placental crossing, selected tyrosine kinase inhibitors (imatinib and nilotinib) seem to be safe and effective options in 2nd and 3rd trimester while hydroxycarbamide offers few benefits.

Oral Galvanism Side Effects: Comparing Alloy Ions and Galvanic Current Effects on the Mucosa-like Model.

The interaction of different dental alloys with the oral environment may cause severe side effects (e.g., burning sensation, inflammatory reactions, carcinogenesis) as a result of oral galvanism. However, the pathogenesis of side effects associated with oral galvanism is still unclear, and the effects of direct current and alloy corrosion ions are considered potentially contributing factors. Therefore, the aim of this study was to systemically compare the damaging effects of (1) galvanism as a synergistic process (direct current + corrosion ions), (2) direct current separately, and (3) corrosion ions separately on an in vitro mucosa-like model based on a cell line of immortalized human keratinocytes (HaCaTs) to reveal the factors playing a pivotal role in dental alloys side effects. For this, we chose and compared the dental alloys with the highest risk of oral galvanism: Ti64-AgPd and NiCr-AgPd. We showed that galvanic current may be the leading damaging factor in the cytotoxic processes associated with galvanic coupling of metallic intraoral appliances in the oral cavity, especially in the short-term period (28 days). However, the contribution of corrosion ions (Ni2+) to the synergistic toxicity was also shown, and quite possibly, in the long term, it could be no less dangerous.

The Impact of Commercially Available Dry Mouth Products on the Corrosion Resistance of Common Dental Alloys.

Dental implants are thought to be implanted for life, but throughout their lifespan, they function in aggressive oral environment, resulting in corrosion of the material itself as well as possible inflammation of adjacent tissues. Therefore, materials and oral products for people with metallic intraoral appliances must be chosen carefully. The purpose of this study was to investigate the corrosion behavior of common titanium and cobalt-chromium alloys in interaction with various dry mouth products using electrochemical impedance spectroscopy (EIS). The study showed that different dry mouth products lead to different open circuit potentials, corrosion voltages, and currents. The corrosion potentials of Ti64 and CoCr ranged from -0.3 to 0 V and -0.67 to 0.7 V, respectively. In contrast to titanium, pitting corrosion was observed for the cobalt-chromium alloy, leading to the release of Co and Cr ions. Based on the results, it can be argued that the commercially available dry mouth remedies are more favorable for dental alloys in terms of corrosion compared to Fusayama Meyer's artificial saliva. Thus, to prevent undesirable interactions, the individual characteristics of not only the composition of each patient's tooth and jaw structure, but also the materials already used in their oral cavity and oral hygiene products, must be taken into account.

Clinical Outcomes in Patients With COVID-19 and Hematologic Disease.

BACKGROUND: Patients with hematologic diseases are at higher risk of the SARS-CoV-2 infection and more severe clinical outcomes of the coronavirus disease. CHRONOS19 is an observational prospective cohort study with the aim to determine the short and longer-term clinical outcomes, risk factors for disease severity and mortality, and rates of postinfectious immunity in patients with malignant and nonmalignant hematologic diseases and COVID-19. PATIENTS AND METHODS: Overall, 666 patients were enrolled in the study, of which 626 were included in the final data analysis. The primary endpoint was 30-days all-cause mortality. Secondary endpoints included COVID-19 complications, rates of ICU admission and mechanical ventilation, outcomes of a hematologic disease in SARS-CoV-2 infected patients, overall survival, and risk factors for disease severity and mortality. Data from 15 centers were collected at 30, 90, and 180 days after COVID-19 was diagnosed and were managed using a web-based e-data capture platform. All evaluations were performed in the pre-omicron period of COVID-19 pandemic. RESULTS: Thirty-days all-cause mortality was 18.9%. The predominant cause of death (in 80% of cases) were COVID-19 complications. At 180 days, the majority (70%) of additional deaths were due to hematologic disease progression. At a median follow-up of 5.7 [0.03-19.04] months, 6-months overall survival was 72% [95% CI: 0.69-0.76]. One-third of patients had severe SARS-CoV-2 disease. The rate of ICU admission was 22% with 77% of these patients requiring mechanical ventilation, with poor survival rate. A univariate analysis revealed that older age (≥ 60 years), male sex, malignant hematologic disease, myelotoxic agranulocytosis, transfusion dependence, refractory disease or relapse, diabetes among comorbidities, any complications, especially ARDS alone or in combination with CRS, admission to an ICU, and mechanical ventilation were associated with higher risks of mortality. Treatment of the hematologic disease was changed, postponed, or canceled in 63% of patients. At a longer follow-up (90 and 180 days), the status of the hematologic disease changed in 7.5% of patients. CONCLUSION: Patients with hematologic disease and COVID-19 have high mortality rates, predominantly due to COVID-19 complications. At a longer-term follow-up, no significant impact of COVID-19 on the course of a hematologic disease was revealed.

Age estimation of Russian individuals by teeth using the London Atlas / Análise da estimativa de idade em indivíduos russos utilizando a metodologia London Atlas

Knowing an individual's age is necessary for several situations, both in the living and the deceased. The London Atlas uses dental development and eruption to estimate age. Testing the method in different populations is necessary to assess its performance. This study aimed to assess the performance of the London Atlas method in a Russian sample using panoramic radiographs. A sample of 703 panoramic radiographs of Russian individuals (n = 405 females, 57.61% and n = 298 males, 42.39%) with ages between 8 and 23 years were analyzed. The results showed overestimation in individuals from 8 to 14 years and underestimation from 15 to 23 years. The mean difference between estimated and chronological ages did not exceed 0.7 years among individuals with ages below 19 years. The difference increased to over three years in individuals from 20 to 23 years. Statistically significant differences were found between females and males between 17 and 18 years (p<0.05). The London Atlas is suitable for Russian children and adolescents aged between 8 and 19 years; however, it showed unsatisfactory results for application in individuals over 20 years (AU).

Conhecer a idade de um indivíduo, vivo ou morto, é essencial em diversas situações. O método London Atlas utiliza desenvolvimento e erupção dentais para estimar a idade. Testar o método em diferentes populações é importante para avaliar sua performance. Esse estudo objetivou analisar o desempenho do London Atlas em uma amostra de origem russa, utilizando radiografias panorâmicas. Uma amostra de 703 indivíduos russos (n = 405 mulheres, 57,61% e n = 298 homens, 42,39%), com idades entre 8 e 23 anos foram analisadas. Resultados obtidos mostram uma superestimação em indivíduos de 8 a 14 anos e subestimação nos grupos de 15 a 23 anos. A diferença média entre idades estimadas e reais não excederam o valor de 0,7 anos nos indivíduos com idade abaixo de 19 anos. Essa diferença aumentou em até três anos em indivíduos de 20 a 23 anos. Diferenças estatisticamente significantes foram encontradas entre homens e mulheres com 17 e 18 anos (p<0,05). O London Atlas é adequado para crianças e adolescentes de origem russa, com idades de 8 a 19 anos. No entanto, observou-se resultados insatisfatórios para sua aplicação em indivíduos acima de 20 anos (AU).

Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL.

Asciminib, the first BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket (STAMP), is approved worldwide for the treatment of adults with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (CML-CP) treated with ≥2 prior tyrosine kinase inhibitors (TKIs). In ASCEMBL, patients with CML-CP treated with ≥2 prior TKIs were randomized (stratified by baseline major cytogenetic response [MCyR]) 2:1 to asciminib 40 mg twice daily or bosutinib 500 mg once daily. Consistent with previously published primary analysis results, after a median follow-up of 2.3 years, asciminib continued to demonstrate superior efficacy and better safety and tolerability than bosutinib. The major molecular response (MMR) rate at week 96 (key secondary endpoint) was 37.6% with asciminib vs 15.8% with bosutinib; the MMR rate difference between the arms, after adjusting for baseline MCyR, was 21.7% (95% CI, 10.53-32.95; two-sided p = 0.001). Fewer grade ≥3 adverse events (AEs) (56.4% vs 68.4%) and AEs leading to treatment discontinuation (7.7% vs 26.3%) occurred with asciminib than with bosutinib. A higher proportion of patients on asciminib than bosutinib remained on treatment and continued to derive benefit over time, supporting asciminib as a standard of care for patients with CML-CP previously treated with ≥2 TKIs.

Minimization of Adverse Effects Associated with Dental Alloys.

Metal alloys are one of the most popular materials used in current dental practice. In the oral cavity, metal structures are exposed to various mechanical and chemical factors. Consequently, metal ions are released into the oral fluid, which may negatively affect the surrounding tissues and even internal organs. Adverse effects associated with metallic oral appliances may have various local and systemic manifestations, such as mouth burning, potentially malignant oral lesions, and local or systemic hypersensitivity. However, clear diagnostic criteria and treatment guidelines for adverse effects associated with dental alloys have not been developed yet. The present comprehensive literature review aims (1) to summarize the current information related to possible side effects of metallic oral appliances; (2) to analyze the risk factors aggravating the negative effects of dental alloys; and (3) to develop recommendations for diagnosis, management, and prevention of pathological conditions associated with metallic oral appliances.

The Electrical Activity of the Orbicularis Oris Muscle in Children with Down Syndrome-A Preliminary Study.

The aim of this study was to assess the electrical activity of the superior (SOO) and inferior (IOO) orbicularis oris muscles in children with Down syndrome (DS) and in children without DS. After applying the inclusion and exclusion criteria, 30 subjects were eligible to participate in the later stages of the research-15 subjects with DS (mean age 10.1 ± 1.1) and 15 healthy controls (mean age 9.8 ± 1.0). The electrical potentials of the SOO and IOO muscles were recorded using a DAB-Bluetooth electromyography machine (Zebris Medical GmbH, Germany) during the following tasks: At clinical rest, saliva swallowing, lip protrusion, lip compression, and production of the syllable/pa/. The Mann-Whitney U test was conducted to compare the study results between the groups. An analysis of the electromyographical (EMG) recordings showed that the electrical activity of the orbicularis oris muscle in children with DS and lip incompetence was significantly higher compared to healthy children during saliva swallowing, lip compression, and when producing the syllable/pa/, and this may suggest greater muscular effort due to the need to seal the lips during these functional conditions.

Ponatinib dose-ranging study in chronic-phase chronic myeloid leukemia: a randomized, open-label phase 2 clinical trial.

In PACE (Ponatinib Ph+ ALL and CML Evaluation), a phase 2 trial of ponatinib that included patients with chronic-phase chronic myeloid leukemia (CP-CML) resistant to multiple prior tyrosine kinase inhibitors (TKIs), ponatinib showed deep and durable responses, but arterial occlusive events (AOEs) emerged as notable adverse events. Post hoc analyses indicated that AOEs are dose dependent. We assessed the benefit/risk ratio across 3 ponatinib starting doses in the first prospective study to evaluate a novel, response-based, dose-reduction strategy for TKI treatment. Adults with CP-CML resistant to or intolerant of at least 2 prior BCR-ABL1 TKIs or with a BCR-ABL1 T315I mutation were randomly assigned 1:1:1 to 3 cohorts receiving ponatinib 45, 30, or 15 mg once daily. In patients who received 45 or 30 mg daily the dose was reduced to 15 mg upon response (BCR-ABL1IS transcript levels ≤1%). The primary end point was response at 12 months. From August 2015 through May 2019, 283 patients were randomly assigned to the cohorts: 282 (94 per dose group) received treatment (data cutoff, 31 May 2020). The primary end point (98.3% confidence interval) was achieved in 44.1% (31.7-57.0) in the 45-mg cohort, 29.0% (18.4-41.6) in the 30-mg cohort, and 23.1% (13.4-35.3) in the 15-mg cohort. Independently confirmed grade 3 or above treatment-emergent AOEs occurred in 5, 5, and 3 patients in the 45-, 30-, and 15-mg cohorts, respectively. All cohorts showed benefit in this highly resistant CP-CML population. Optimal benefit/risk outcomes occurred with the 45-mg starting dose, which was decreased to 15 mg upon achievement of a response. This trial is registered on www.clinicaltrials.gov as NCT02467270.

A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs.

Patients with chronic myeloid leukemia in chronic phase (CML-CP) resistant/intolerant to ≥2 tyrosine kinase inhibitors (TKIs) are at high risk of experiencing poor outcomes because of disease biology and inadequate efficacy and/or safety of current therapies. Asciminib, a first-in-class BCR-ABL1 inhibitor Specifically Targeting the ABL Myristoyl Pocket (STAMP), has the potential to overcome resistance/intolerance to approved TKIs. In this phase 3, open-label study, patients with CML-CP previously treated with ≥2 TKIs were randomized (2:1) to receive asciminib 40 mg twice daily vs bosutinib 500 mg once daily. Randomization was stratified by major cytogenetic response (MCyR) status at baseline. The primary objective was to compare the major molecular response (MMR) rate at week 24 for asciminib vs bosutinib. A total of 233 patients were randomized to asciminib (n = 157) or bosutinib (n = 76). Median follow-up was 14.9 months. The MMR rate at week 24 was 25.5% with asciminib and 13.2% with bosutinib. The difference in MMR rate between treatment arms, after adjusting for MCyR at baseline, was 12.2% (95% confidence interval, 2.19-22.30; 2-sided P = .029). Fewer grade ≥3 adverse events (50.6% vs 60.5%) and adverse events leading to treatment discontinuation (5.8% vs 21.1%) occurred with asciminib than with bosutinib. The study showed a superior efficacy of asciminib compared with that of bosutinib, together with a favorable safety profile. These results support the use of asciminib as a new therapy in patients with CML-CP who are resistant/intolerant to ≥2 prior TKIs. This trial was registered at www.clinicaltrials.gov as #NCT03106779.

Long-term treatment-free remission in patients with chronic myeloid leukemia after second-line nilotinib: ENESTop 5-year update.

The ENESTop study evaluated treatment-free remission (TFR) in patients with chronic myeloid leukemia (CML) in chronic phase who had received ≥3 years of tyrosine kinase inhibitor therapy and achieved sustained deep molecular response only after switching from imatinib to nilotinib. After 1-year nilotinib consolidation, 126 patients attempted TFR. At 48 weeks (primary analysis), 57.9% (73/126) were in TFR. In the present analysis at 5 years, 42.9% (54/126) were in TFR. Since the 48-week analysis, among patients who left the TFR phase, 58% (11/19) did not have a loss of molecular response and discontinued for other reasons. Of the 59 patients who reinitiated nilotinib upon loss of major molecular response (MMR) or confirmed loss of MR4, 98.3% regained MMR, 94.9% regained MR4, and 93.2% regained MR4.5. Overall adverse event rates decreased over the 5 years of TFR. In patients reinitiating nilotinib, there was a cumulative increase in cardiovascular events with longer nilotinib exposure. No disease progression or CML-related deaths were reported. Overall, these results confirm the durability and safety of TFR for patients receiving second-line nilotinib. Cardiovascular risk should be carefully managed, particularly when reinitiating treatment after TFR.

Radiographic assessment of third molar development in a Russian population to determine the age of majority.

OBJECTIVE: To test the applicability of "Gleiser and Hunt dental staging system modified by Kohler" (GHK) to assess third molar (3 M) development in a Russian population in order to determine the age of majority. DESIGN: The sample consisted of 918 panoramic radiographs from Russian females (n = 551) and males (n = 367) within the age interval between 8 and 23 years. On each radiograph, 3 M development was classified based on the GHK technique. Statistics tested the data for normality. Mean age and standard deviation were described for each 3 M position. Ordinal logistic regression tested the performance of the technique to classify individuals below or above the 18-year threshold. Receiver Operating Characteristic (ROC) curves were used. RESULTS: The mean ages and standard deviation (SD) for apex closure in females were 21,11 (SD = 1,47), 21,11 (SD = 1,43), 21,24 (SD = 1,39), and 21,29 (SD = 1,28) years for the teeth #18, 28, 38, and 48, respectively. Among males, the same teeth showed mean closure ages of 20,57 (SD = 1,69), 20,64 (SD = 1,76), 20,68 (SD = 1,68), and 20,81 (SD = 1,62) years, respectively. Area under the curve (AUC) reached 0.904 and 0.915 for classifying females and males below or above the 18-year threshold. CONCLUSION: The GHK technique was able to describe 3 M development in a Russian population. The statistic model was able to classify individuals below or above the 18-year threshold. However, the outcomes must be carefully interpreted, especially in borderline cases (17-19-year spectrum).

Xerostomia and hyposalivation in patients with obstructive sleep apnoea.

OBJECTIVE: (a) To report the xerostomia prevalence and severity in patients with obstructive sleep apnoea (OSA). (b) To assess the saliva pH in patients with OSA. DESIGN: Simultaneous cohort observational clinical study. SETTING: In Sleep Medicine Centre at Lomonosov Moscow State University from March to June 2019. PARTICIPANTS: The study was conducted on 30 patients with OSA aged from 35 to 65 years. MAIN OUTCOMES MEASURES: The diagnosis of sleep apnoea was made after standard polysomnography using the Domino programme. The severity of OSA was indicated using the Apnoea-Hypopnea Index. Xerostomia was evaluated using Fox's test. Hyposalivation was evaluated by measurement of salivary flow rate. Determination of the saliva pH was carried out with a pH metre. Statistical analysis was performed by one-way ANOVA and Tukey-Kramer multi-comparison test. RESULTS: Twenty-two out of 30 (73.3%) patients were diagnosed with "dry mouth". Hyposalivation was observed in 6 out of 30 (20%). Dry mouth on awakening was observed in 60.0%, 72.7% and 88.9% of patients with mild, moderate and severe OSA, respectively. The average salivary flow rate was 0.28 mL/min, 0.24 mL/min and 0.14 mL/min, respectively. The average pH value in patients with mild, moderate and severe apnoea was 6.40 ± 0.017, 6.15 ± 0.27 and 5.87 ± 0.24, respectively. CONCLUSIONS: In patient with mild and moderate OSA, the saliva amount and rate are similar (P > .05). With the increase of OSA severity, both these parameters change (P < .001). The acidity of the saliva was correlated with the level of OSA, and it statistically increased with the increment of the OSA severity (P < .05-P < .001).

Treatment of an Endo-Perio Lesion with Ozone Gas in a Patient with Aggressive Periodontitis: A Clinical Case Report and Literature Review.

The pulp and periodontium have obvious relationships that have been described in many studies. Pulp infections may affect periodontal tissues and vice versa. Teeth with endo-perio lesions have a worse prognosis than isolated endodontic or periodontal lesions. Elimination of endodontic and periodontal infections is essential for successful treatment, so co-operation between endodontists and periodontists is necessary. In this clinical case, a 44-year-old male presented with primary periodontal disease with secondary endodontic involvement in his lower right canine because of aggressive periodontitis. There was 10 mm of clinical attachment loss and 8 mm periodontal pocket mesial from the tooth and bone radiolucency periapical and lateral from the root. Periodontal therapy was followed by endodontic treatment. Periodontal therapy included root scaling and planing, treatment of the periodontal pocket with ozone gas, systemic antibiotics, oral hygiene instructions, and chlorhexidine rinsing. Endodontic therapy included root canal instrumentation with rotary endodontic files, irrigation, root canal treatment with ozone gas, and obturation with lateral compaction. Radiographs at a 6-month follow-up appointment showed complete healing of the periapical lesion and alveolar bone lateral to the root. Using an interdisciplinary approach to treat endo-perio lesions provides favorable clinical outcomes. Ozone therapy is beneficial for the successful treatment of endo-perio lesions with narrow periodontal pockets in patients with aggressive periodontitis and poor prognosis.

The EUTOS long-term survival (ELTS) score is superior to the Sokal score for predicting survival in chronic myeloid leukemia.

Prognostic scores support clinicians in selecting risk-adjusted treatments and in comparatively assessing different results. For patients with chronic-phase chronic myeloid leukemia (CML), four baseline prognostic scores are commonly used. Our aim was to compare the prognostic performance of the scores and to arrive at an evidence-based score recommendation. In 2949 patients not involved in any score development, higher hazard ratios and concordance indices in any comparison demonstrated the best discrimination of long-term survival with the ELTS score. In a second step, of 5154 patients analyzed to investigate risk group classification differences, 23% (n = 1197) were allocated to high-risk by the Sokal score. Of the 1197 Sokal high-risk patients, 56% were non-high-risk according to the ELTS score and had a significantly more favorable long-term survival prognosis than the 526 high-risk patients according to both scores. The Sokal score identified too many patients as high-risk and relatively few (40%) as low-risk (versus 60% with the ELTS score). Inappropriate risk classification jeopardizes optimal treatment selection. The ELTS score outperformed the Sokal score, the Euro, and the EUTOS score regarding risk group discrimination. The recent recommendation of the European LeukemiaNet for preferred use of the ELTS score was supported with significant statistical evidence.

May VelScope Be Deemed an Opportunistic Oral Cancer Screening by General Dentists? A Pilot Study.

Early diagnosis of oral cancer through visual inspection followed by histopathological confirmation is a pivotal step for reducing rates of morbidity and mortality. There are several auxiliary devices used to improve oral examination. The purpose of this cross-sectional pilot study is to evaluate the sensitivity and specificity of the Visually Enhance Lesion Scope (VelScope) system when it is used by the general dentist after a yearly oral medicine training. Thirty-five patients with oral lesions were evaluated with clinical and VelScope examination by two general dentists, one of which trained with a specific course. A comparison of the histopathological results, clinical examination, and VelScope made by both dentists was performed through statistical analysis. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for detecting oral potentially malignant disorders (OPMDs) are 53.3%, 65%, 53.3%, 76.5% for unskilled dentist, 73.3%, 65%, 61.1%, 76.5% for skilled clinician. When both examiners use VelScope the values are 53.3%, 70%, 57.1%, 66.7% for unskilled general dentist (u-GD), 86.7%, 90%, 86.7%, 90% for skilled general dentist (s-GD). Improvement of a skilled general dentist for detecting malignancies is higher than inexperienced examiner when using VelScope. VelScope alone is unable to improve the general dentist's ability to detect malignancies, but it could be a useful adjunctive device for clinicians when a focused training program is performed.

TARGET: a survey of real-world management of chronic myeloid leukaemia across 33 countries.

Despite the availability of guidelines for the management of chronic myeloid leukaemia (CML), various issues may prevent their successful implementation. The TARGET survey examined real-world management of CML patients compared with international recommendations. This online survey was completed in 2017. Results were discussed by a Steering Committee (SC) of eight international haematologists, challenges were identified and practical solutions developed. Of the 1008 haematologists invited (33 countries), 614 completed the survey. Gaps regarding treatment efficacy and molecular monitoring were identified. Half of the physicians did not perform three-monthly testing of during the initial 12 months of treatment, citing cost as the major barrier, although they know it should be done. Treatment-free remission was not considered a primary treatment goal or as a priority factor influencing treatment decisions. European Leukemia Net guidelines interpretation was generally acceptable, but awareness regarding management of persistent adverse events was poor. Practical solutions proposed by the SC were mostly focused on enhancing physician education and awareness, or encouraging hospitals to work with the government, in order to improve the quality of BCR-ABL testing. Gaps in current CML management were identified compared with international recommendations, which the proposed practical solutions would help to address.

Analysis of the Mortality of Russian Patients With Chronic Myeloid Leukemia in the Multicenter EUTOS ELN Population-based Study (EUTOS-PBS).

INTRODUCTION: Russia took part in the multicenter population-based study (Europe) and included 6.8% adult patients with newly diagnosed chronic myeloid leukemia (CML). The objective of this study was to analyze the mortality in the Russian cohort of patients with newly diagnosed CML in the EUTOS PBS observational study. PATIENTS AND METHODS: The analyzed cohort consisted of 197 patients (>18 years) with Ph+/BCR-ABL1+ CML diagnosed in the period from October 1, 2009 through December 31, 2012 from 6 regions of Russia. The distribution of the phases of CML were: chronic phase (CP), 93.4% and accelerated phase (AP) + blast crisis (BC), 6% + 0.6%. The median age was 50 years (range, 18-82 years); the male/female ratio was equal. RESULTS: The overall survival (OS) at 5, 6, and 7 years was 80% (95% confidence interval [CI], 72%-86%), 78% (95% CI, 65%-80%), and 73% (95% CI, 65%-80%), respectively (P < .001). The 5-year OS in patients with AP and BC was 39%. In Russia, the study was prolonged, with a median follow-up of 77 months (range, 0.7-108 months): 141 (71.5%) patients were alive, 47 (24%) patients died, and the status of 9 (4.5%) patients is was unknown. Forty-seven (23.8%) patients died during the follow-up period. The largest number of deaths was observed in the first year after the CML diagnosis: 17 (36%) of 47 cases, 3 of 17 died refusing the CML treatment. At the seventh year of CML therapy, 1 patient died after allogenic hematopoietic stem cell transplantation. The causes of death were: (1) progression of CML to AP/BC in 20 (43%) patients; (2) death in remission in 5 (11%) patients with complete cytogenetic response (CCyR) and/or major molecular response; and (3) death without progression to AP/BC but with signs of leukemia in 22 (46%) patients. The 5-year cumulative incidence of death from all reasons was 20%; the cumulative incidence of CML-related and non-CML-related death at the fifth year was 18% and 11%, respectively. CONCLUSION: In general, the results of treatment in the Russian population sample of non-selected patients with CML were comparable with the data of the total European cohort. The CML-related deaths prevailed in the first year of CML therapy. The appropriate monitoring and therapy interventions during the first year of CML treatment are apparently important for the long-term treatment results.

Withdrawal Syndrome After Tyrosine Kinase Inhibitor Discontinuation in Patients With Chronic Myeloid Leukemia in the Russian Prospective Study RU-SKI.

We aimed to characterize withdrawal syndrome (WS) and evaluate factors associated with its development in the prospective clinical study RU-SKI in patients with chronic myeloid leukemia with deep molecular response who discontinued tyrosine kinase inhibitor (TKI) therapy. In total, 98 adult patients with chronic myeloid leukemia chronic phase, TKI therapy ≥ 3 years, and deep molecular response (BCR-ABL ≤ 0.01%) ≥ 2 years were enrolled and observed without treatment. WS was defined as newly observed or worsening musculoskeletal pain after TKI cessation. WS symptoms were found in 41 (42%) of 98 patients with a median time of observation of 25 months (range, 12-42 months). WS grades 1 to 2 and grade 3 were observed in 39 (95%) and in 2 (5%) patients, respectively. The median duration of WS was 5 months (range, 1-25 months). WS was resolved in 37 (90%) patients. Anti-inflammatory therapy was used in 21 (51%) patients. Older age (P = .039) and longer TKI therapy (P = .001) were associated with WS. The 2-month landmark analysis found no association of WS development and the rate of molecular relapses. In total, 42% of the patients experienced WS after TKI therapy discontinuation in the RU-SKI study. Physicians should be warned about the possibility of WS development, and patients of older age and with longer TKI treatment need special attention.