Risk Of Further Progression Research Articles

The Effect of Stress-Reducing Interventions on Heart Rate Variability in Cardiovascular Disease: A Systematic Review and Meta-Analysis.

Stress is recognized as a significant trigger and exacerbator of various medical conditions, particularly in the field of cardiovascular disease (CVD). Given that heart rate variability (HRV) offers insight into the functioning of the autonomic nervous system and has been identified as a predictive factor for increased cardiovascular mortality, exploring the correlation between stress and HRV is pertinent. We systematically reviewed trials where researchers investigated the effects of stress-reducing interventions on biomarkers and time-domain/frequency-domain parameters of HRV in CVD. Eligible studies underwent meta-analysis utilizing a random-effects model. The meta-analysis showed overall beneficial effects of stress-reducing interventions on HRV for the standard deviation of Normal-to-Normal intervals (SDNN) in short-term and 24 h assessments, as well as for the low-frequency power (LF) in short-term assessment. Overall effect sizes were notably high and showed significant p-values (short-term SDNN: MD = 6.43, p = 0.01; 24 h SDNN: MD = 10.92, p = 0.004; short-term LF: MD = 160.11, p < 0.001). Our findings highlight the significant impact of stress-reducing interventions in modulating HRV by influencing short-term SDNN and LF parameters, as well as the 24 h assessment of SDNN. These results emphasize the importance of stress-reducing measures in lowering the risk of further progression in CVD and improving patient outcomes.

Risk of Further Progression or Death Among Durable Progression-Free Survivors With Melanoma or Non-Small-Cell Lung Cancer in PD-1 Blockade Trials: Implications for Imaging Surveillance.

Durable progression-free survivors (dPFSors) over 2 years have been reported among patients with melanoma or non-small-cell lung cancer (NSCLC) who received PD-(L)1 therapy. However, risk of progression still exists and the optimal imaging surveillance interval is unknown. Individual patient data for progression-free survival (PFS) were extracted from PD-1 blockade clinical trials with a follow-up of at least 5 years. Patients with a PFS of at least 2 years were considered as dPFSors. Conditional risks of progression/death (P/D) every 3, 4, 6, and 12 months in each subsequent year were calculated. We prespecified three different levels of risk between scans (10%, 15%, or 20%) to allow clinicians and patients to decide on the scanning interval on the basis of considerations of imaging frequency and risk tolerance. An interval is considered acceptable if the upper bound of the 95% CI of the risk at each scan is lower than a prespecified level. Of 1,495 and 3,752 patients with melanoma and NSCLC, 474 (31.7%) and 586 (15.6%) were dPFSors, respectively. Among them, the PFS probability for an additional 3 years was 76.4% and 48.1%, respectively. Not more than 8% of patients had P/D in any quarter in the 3 years. With a risk threshold of 10%, melanoma dPFSors can be scanned every 6 months during the third year and then every 12 months in years 4 and 5. The interval for NSCLC would be every 3 months in the third year and every 4 months in years 4 and 5. The higher risk tolerance of 15% and 20% would allow for less frequent scans. On the basis of their own risk tolerance level, our findings allow clinicians and dPFSors make data-driven decisions regarding the imaging surveillance schedule beyond every 3 months.

Risk of further progression or death among durable progression-free survivors with melanoma in PD-1 blockade trials: Implications for imaging surveillance.

9529 Background: Durable progression-free survivors (dPFSors) over 2 years have been reported among melanoma patients treated with PD-1 blockade. However, non-negligible risk of further progression still exists and the optimal imaging surveillance interval is unknown. Methods: Individual patient data of progression-free survival (PFS) were extracted from PD-1 blockade clinical trials with follow-up of at least 5 years of PFS events. Co-treatment with anti-CTLA4 antibody was allowed. Patients with PFS of at least 2 years were considered as dPFSors. Conditional risk of progression or death with 95% CI was estimated based on a piece-wise exponential survival model, with the assumption that within each year from the beginning of the third year, the risk of progression/death (P/D) was constant. Conditional risks of P/D every 3, 4, 6, and 12 months in each subsequent year were calculated with 95% confidence interval (CI). We pre-specified three maximal risk levels – 10%, 15%, and 20% at each imaging scanning interval. An interval is considered as acceptable if the 95% CI upper bound of the risk at each scan is lower than a pre-specified risk level. Results: Of 1495 melanoma patients from 3 clinical trials, 474 (31.7%) were dPFSors. Among them, the PFS probability for additional 3 years was 76.4%. During the 3 years, no more than 5.0% of patients had P/D in any quarters. The yearly risk of P/D was 15.5% (95% CI 13.7% - 17.3%), 8.8% (6.8% - 10.8%), and 6.3% (3.8% - 8.8%) during the 3rd, 4th, and 5th year, respectively. Under risk at 10%, 15%, and 20%, melanoma dPFSors can be scanned every 6, 6, and 12 months during the 3rd year, every 6, 12, and 12 months during the 4th, and every 12, 12, and 12 months during the 5th, respectively. Conclusions: Based on their own risk tolerance level, our findings allow clinicians and dPFSors make data-driven decisions regarding imaging surveillance schedule beyond every 3 months. [Table: see text]

Случаи отсутствия лечебного эффекта кросслинкинга при лечении кератоконуса

Purpose. Study of changes in morphometric parameters of cornea in keratoconus before and after corneal collagen crosslinking (CXL). Material and methods. 35 patients (35 eyes) with progressive keratoconus stages 1–3. The indexes of photokeratoscopy were studied in depth (topographer Pentacam (Oculus, Germany). CXL was performed according to the Dresden protocol. A corneal lenticule was used in 6 eyes. The analysis of the studied parameters was carried out initially and after 12 months. Results. By the end of the observation, in all patients, the average values of maximum keratometry (Kmax) decreased statistically significantly from 54.5 to 53.1 diopters, which indicated positive trend. Most indices of keratoconus according to topographer data (ISV, IVA, KI, CKI, IHA, Rmin), as well as the central corneal thickness, on average, significantly decreased. But in 5 patients (all men, mean age 25 years), the Kmax exceeded initial values (from 61.7 to 64.5 diopters), which indicated further progression of keratoconus. The initial values of Kmax in 3 out of 5 of these patients exceeded 57 diopters, which is risk of further progression of keratoconus. Conclusion. With a follow-up period of one year, it was found that CXL in 5 patients (14 %) with keratoconus stages 2-3 turned out to be ineffective. Keywords: keratoconus, photokeratoscopy, corneal collagen crosslinking

ESTRO-ACROP recommendations for evidence-based use of androgen deprivation therapy in combination with external-beam radiotherapy in prostate cancer

Background and purposeThere is no consensus concerning the appropriate use of androgen deprivation therapy (ADT) during primary and postoperative external-beam radiotherapy (EBRT) in the management of prostate cancer (PCa). Thus, the European Society for Radiotherapy and Oncology (ESTRO) Advisory Committee for Radiation Oncology Practice (ACROP) guidelines seeks to present current recommendations for the clinical use of ADT in the various indications of EBRT. Material and methodsA literature search was conducted in MEDLINE PubMed that evaluated EBRT and ADT in prostate cancer. The search focused on randomized, Phase II and III trials published in English from January 2000 to May 2022. In case topics were addressed in the absence of Phase II or III trials, recommendations were labelled accordingly based on the limited body of evidence. Localized PCa was classified according to D’Amico et al. classification in low-, intermediate and high risk PCa. The ACROP clinical committee identified 13 European experts who discussed and analyzed the body of evidence concerning the use of ADT with EBRT for prostate cancer. ResultsKey issues were identified and are discussed: It was concluded that no additional ADT is recommended for low-risk prostate cancer patients, whereas for intermediate- and high-risk patients four to six months and two to three years of ADT are recommended. Likewise, patients with locally advanced prostate cancer are recommended to receive ADT for two to three years and when ≥ 2 high-risk factors (cT3-4, ISUP grade ≥ 4 or PSA ≥ 40 ng/ml) or cN1 is present ADT for three years plus additional Abiraterone for two years is recommended. For postoperative patients no ADT is recommended for adjuvant EBRT in pN0 patients whereas for pN1 patients adjuvant EBRT with long-term ADT is performed for at least 24 to 36 months. In the setting of salvage EBRT ADT is performed in biochemically persistent PCa patients with no evidence of metastatic disease. Long-term ADT (24 months) is recommended in pN0 patients with high risk of further progression (PSA ≥ 0.7 ng/ml and ISUP grade group ≥ 4) and a life expectancy of over ten years, whereas short-term ADT (6 months) is recommended in pN0 patients with lower risk profile (PSA < 0.7 ng/ml and ISUP grade group 4). Patients considered for ultra-hypofractionated EBRT as well as patients with image based local recurrence within the prostatic fossa or lymph node recurrence should participate in appropriate clinical trials evaluating the role of additional ADT. ConclusionThese ESTRO-ACROP recommendations are evidence-based and relevant to the use of ADT in combination with EBRT in PCa for the most common clinical settings.

Periodontal treatment and microbiome-targeted therapy in management of periodontitis-related nonalcoholic fatty liver disease with oral and gut dysbiosis.

A growing body of evidence from multiple areas proposes that periodontal disease, accompanied by oral inflammation and pathological changes in the microbiome, induces gut dysbiosis and is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). A subgroup of NAFLD patients have a severely progressive form, namely nonalcoholic steatohepatitis (NASH), which is characterized by histological findings that include inflammatory cell infiltration and fibrosis. NASH has a high risk of further progression to cirrhosis and hepatocellular carcinoma. The oral microbiota may serve as an endogenous reservoir for gut microbiota, and transport of oral bacteria through the gastro-intestinal tract can set up a gut microbiome dysbiosis. Gut dysbiosis increases the production of potential hepatotoxins, including lipopolysaccharide, ethanol, and other volatile organic compounds such as acetone, phenol and cyclopentane. Moreover, gut dysbiosis increases intestinal permeability by disrupting tight junctions in the intestinal wall, leading to enhanced translocation of these hepatotoxins and enteric bacteria into the liver through the portal circulation. In particular, many animal studies support that oral administration of Porphyromonas gingivalis, a typical periodontopathic bacterium, induces disturbances in glycolipid metabolism and inflammation in the liver with gut dysbiosis. NAFLD, also known as the hepatic phenotype of metabolic syndrome, is strongly associated with metabolic complications, such as obesity and diabetes. Periodontal disease also has a bidirectional relationship with metabolic syndrome, and both diseases may induce oral and gut microbiome dysbiosis with insulin resistance and systemic chronic inflammation cooperatively. In this review, we will describe the link between periodontal disease and NAFLD with a focus on basic, epidemiological, and clinical studies, and discuss potential mechanisms linking the two diseases and possible therapeutic approaches focused on the microbiome. In conclusion, it is presumed that the pathogenesis of NAFLD involves a complex crosstalk between periodontal disease, gut microbiota, and metabolic syndrome. Thus, the conventional periodontal treatment and novel microbiome-targeted therapies that include probiotics, prebiotics and bacteriocins would hold great promise for preventing the onset and progression of NAFLD and subsequent complications in patients with periodontal disease.

PPD04.03 Risk of Further Progression or Death among Non-small Cell Lung Cancer Patients with Durable Disease Control Enrolled in Immunotherapy Trials

PPD04.03 Risk of Further Progression or Death among Non-small Cell Lung Cancer Patients with Durable Disease Control Enrolled in Immunotherapy Trials

Retinopathy During the First 5 Years of Type 1 Diabetes and Subsequent Risk of Advanced Retinopathy.

To determine whether individuals with type 1 diabetes (T1D) who develop any retinopathy at any time prior to 5 years of diabetes duration have an increased subsequent risk for further progression of retinopathy or onset of proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), diabetes-related retinal photocoagulation, or anti-vascular endothelial growth factor injections. Additionally, to determine the influence of HbA1c and other risk factors in these individuals. Diabetic retinopathy (DR) was assessed longitudinally using standardized stereoscopic seven-field fundus photography at time intervals of 6 months to 4 years. Early-onset DR (EDR) was defined as onset prior to 5 years of T1D duration. Cox models assessed the associations of EDR with subsequent risk of outcomes. In unadjusted models, individuals with EDR (n = 484) had an increased subsequent risk of PDR (hazard ratio [HR] 1.51 [95% CI 1.12, 2.02], P = 0.006), CSME (HR 1.44 [1.10, 1.88], P = 0.008), and diabetes-related retinal photocoagulation (HR 1.48 [1.12, 1.96], P = 0.006) compared with individuals without EDR (n = 369). These associations remained significant when adjusted for HbA1c, but only the association with PDR remained significant after adjustment for age, duration of T1D, HbA1c, sex, systolic/diastolic blood pressure, pulse, use of ACE inhibitors, albumin excretion rate, and estimated glomerular filtration rate (HR 1.47 [95% CI 1.04, 2.06], P = 0.028). These data suggest that individuals with any sign of retinopathy within the first 5 years of T1D onset may be at higher risk of long-term development of advanced DR, especially PDR. Identification of early-onset DR may influence prognosis and help guide therapeutic management to reduce the risk of future visual loss in these individuals.

Clinical course of non-alcoholic fatty liver disease and the implications for clinical trial design.

The predicted risk and timeline to progression to liver-related outcomes in the population with NAFLD are not well-characterized. We aimed to examine the risk and time to progression to cirrhosis, hepatic decompensation and death in a contemporary population over a long follow-up period, to obtain information to guide endpoint selection and sample size calculations for clinical trials on NAFLD-related cirrhosis. This is a retrospective study of prospectively collected data in a medical record linkage system, including all adults diagnosed with NAFLD between 1996-2016 by clinical, biochemical and radiological criteria in Olmsted County, Minnesota and followed until 2019. Liver-related outcomes and death were ascertained and validated by individual medical record review. Time and risk of progression from NAFLD to cirrhosis to decompensation and death were assessed using multistate modeling. A total of 5,123 individuals with NAFLD (median age 52 years, 53% women) were followed for a median of 6.4 (range 1-23) years. The risk of progression was as follows: from NAFLD to cirrhosis: 3% in 15 years; compensated cirrhosis to first decompensation: 33% in 4 years (8%/year); first decompensation to ≥2 decompensations: 48% in 2 years. Albumin, bilirubin, non-bleeding esophageal varices and diabetes were independent predictors of decompensation. Among the 575 deaths, 6% were liver related. Therapeutic trials in compensated cirrhosis would require enrolment of a minimum of 2,886 individuals followed for >2 years to detect at least a 15% relative decrease in liver-related endpoints. In this population-based cohort with 23 years of longitudinal follow-up, NAFLD was slowly progressive, with liver-related outcomes affecting only a small proportion of people. Large sample sizes and long follow-up are required to detect reductions in liver-related endpoints in clinical trials. For patients with compensated non-alcoholic steatohepatitis-related cirrhosis, the time spent in this state and the risk of progression to decompensation are not well-known in the population. We examined the clinical course of a large population-based cohort over 23 years of follow-up. We identified that adults with compensated cirrhosis spend a mean time of 4 years in this state and have a 10% per year risk of progression to decompensation or death. The risk of further progression is 3-fold higher in adults with cirrhosis and one decompensating event. These results are reflective of placebo arm risks in drug clinical trials and are essential in the estimation of adequate sample sizes.

Factors Influencing the Outcome of Head and Neck Cancer of Unknown Primary (HNCUP).

Background: This study on patients with head and neck cancer of unknown primary (HNCUP) assesses the impact of surgical and non-surgical treatment modalities and the tumour biology on the oncological outcome. Methods: A total of 80 patients with HNCUP (UICC I–IV) were treated with simultaneous neck dissection followed by adjuvant therapy, between 1 January 2007 and 31 March 2020. As the primary objective, the influence of treatment modalities on the overall survival (OS), the disease-specific survival (DSS) and the progression-free survival (PFS) were analysed in terms of cox regression and recursive partitioning. The tumour biology served as secondary objectives. Results: The 5-year OS for the entire cohort was 67.7%, (95% CI: 54.2–81.2%), the 5-year DSS was 82.3% (72.1–92.5%) and the 5-year PFS was 72.8% (61.8–83.8%). Cox regression revealed that patients undergoing adjuvant radiotherapy only had a four times higher risk to die compared to patients receiving chemoradiation therapy (HR = 4.45 (1.40; 14.17), p = 0.012). The development of distant metastases had a significantly negative impact on OS (HR = 8.24 (3.21–21.15), p < 0.001) and DSS (HR = 23.79 (6.32–89.56), p < 0.001). Recursive portioning underlined the negative influence of distant metastases on OS (3.2-fold increase in death probability) and DSS (4.3-fold increase in death probability), while an UICC stage of IVb increased the risk for further progression of the disease by a factor of 2. Conclusions: The presence of distant metastases as well as adjuvant treatment with radiation without concomitant chemotherapy, were among others, significant predictors for the overall survival of HNCUP patients, with distant metastases being the most significant predictor.

Mitochondria and the NLRP3 Inflammasome in Alcoholic and Nonalcoholic Steatohepatitis.

Alcoholic (ASH) and nonalcoholic steatohepatitis (NASH) are advanced stages of fatty liver disease and two of the most prevalent forms of chronic liver disease. ASH and NASH are associated with significant risk of further progression to cirrhosis and hepatocellular carcinoma (HCC), the most common type of liver cancer, and a major cause of cancer-related mortality. Despite extensive research and progress in the last decades to elucidate the mechanisms of the development of ASH and NASH, the pathogenesis of both diseases is still poorly understood. Mitochondrial damage and activation of inflammasome complexes have a role in inducing and sustaining liver damage. Mitochondrial dysfunction produces inflammatory factors that activate the inflammasome complexes. NLRP3 inflammasome (nucleotide-binding oligomerization domain-like receptor protein 3) is a multiprotein complex that activates caspase 1 and the release of pro-inflammatory cytokines, including interleukin-1β (IL-1β) and interleukin-18 (IL-18), and contributes to inflammatory pyroptotic cell death. The present review, which is part of the issue “Mitochondria in Liver Pathobiology”, provides an overview of the role of mitochondrial dysfunction and NLRP3 activation in ASH and NASH.

Complement component 3 and its activation split‐products in saliva associate with periodontitis

Periodontitis (PD) is classified by Grades A through C according to the risk of further progression, PD Grade C (PD-C) being the most severe progressing form. It is a matter of controversy, whether the disease activity observed in PD-C is due to impaired immune reactivity toward bacteria embedded in biofilms or a hyper-reactive immune response causing tissue damage as a bystander phenomenon. Little is known about the role of complement in this respect. Plasma and unstimulated saliva samples were collected from patients with PD-B (n=34) or -C (n=27) and healthy controls (HCs) (n=28). Salivary and plasma levels of total C3, C3c, and C3dg were quantified using sandwich enzyme-linked immunosorbent assay (ELISA). Salivary levels of total C3 and C3dg were elevated in PD-B and PD-C patients compared to HCs (both P&lt;0.05), while the levels of C3c were elevated in PD-C compared to HCs. Plasma levels of C3c were higher in PD-B patients than in HCs (P&lt;0.05). PD-B and PD-C patients show increased complement activation compared to HCs, but no difference was found between the two disease grades. PD-B, but not PD-C, is associated with increased systemic complement activation as assessed by C3c in plasma.

Impact of tobacco use on corneal thickness and endothelial health: a systematic review with meta-analyses.

To investigate the impact of tobacco use on corneal thickness and corneal endothelial health. We searched the PubMed/MEDLINE, EMBASE, the Cochrane Central and all affiliated databases of the Web of Science on 20 July 2020. Two authors reviewed the studies and extracted the data in an independent fashion. Studies were reviewed qualitatively in the text, and central corneal thickness (CCT) and corneal endothelial characteristics (endothelial cell density, endothelial cell variability, average of endothelial cell size and endothelial cell hexagonality) were introduced for quantitative analyses. Eighteen studies (2077 were smokers and 6429 non-smokers) were identified, of which 17 studies provided data eligible for one or more of the quantitative analyses. When compared to non-smokers, smokers had a higher CCT (+3.3 μm, 95% CI: +0.9 to +5.7 μm, p = 0.007) and a lower endothelial cell density (-140 cells/mm2 , 95% CI: -30 to -250 cells/mm2 , p = 0.01). Other corneal endothelial measures did not differ significantly. Tobacco use is associated with a higher CCT and lower corneal endothelium cell density, but the clinical impact of these findings is small. Further studies are warranted on patients with a priori poor corneal health, where smoking may constitute an important risk of further progression, for example upon anterior segment surgery.

Correlation between stromal cell-derived factor 1 and the prognosis of transient ischemic attack

Background: Transient Ischemic Attack (TIA) (1) is a neurological dysfunction of transient cerebrovascular ischemia, which is more common in clinical practice. The risk of further progression to ischemic stroke after a higher TIA can be used as a strong early warning signal of cerebral infarction. Objectives: To explore the correlation between stromal cell-derived factor 1 (SDF-1) and the prognosis of TIA. Methods: A number of 65 patients with TIA were collected, the ABCD2 clinical risk prediction score was implemented, relevant tests and nuclear magnetic resonance imaging (MRI) were performed, and the SDF-1 was recorded in serum levels. End-point events were selected in patients after cerebral infarction in the short term. The statistical analysis method was used to evaluate TIA short-term development for the occurrence of cerebral infarction after risk, the severity of serum level of SDF-1, and infarction. Results: Based on the results, the high-risk group, middle-risk group, and low-risk group had statistically significant differences in serum SDF-1 levels (F=3.820; P&lt;0.05). Correlation analysis demonstrated that ABCD2 score was positively correlated with serum SDF-1 (r=0.349; P&lt;0.05). End-point events were included in the occurrence group and not included in the non-occurrence group. The SDF-1 level of the occurrence group was significantly higher than that of the non-occurrence group. Based on the cranial MRI results as the gold standard, the areas under the curve of the receiver operating characteristic curve (ROC) drawn based on the SDF-1, ABCD2 score, SDF-1 combined with the ABCD2 score, and the occurrence of end-point events were obtained at 0.717, 0.697, and 0.762, respectively. The sensitivity and specificity of SDF-1 were reported as 77.8% and 68.1%, respectively. The sensitivity and specificity of the ABCD2 score were 83.3% and 48.9%, respectively. The sensitivity and specificity of SDF-1 combined with the ABCD2 score were 72.2% and 76.6%, respectively. Conclusion: As evidenced by the obtained results, SDF-1 is associated with ABCD2 score risk classification. Patients with high levels of SDF-1 combined with the ABCD2 score have a higher risk of cerebral infarction. Elevated SDF-1 levels may indicate that TIA patients have a poor short-term prognosis and have a certain predictive value for the diagnosis of the risk of ischemic stroke in the short term.

Clinical and experimental substantiation of the use of bentonite suspension in the complex rehabilitation of patients with chronic viral hepatitis C with concomitant non-alcoholic fatty liver disease

Introduction. One of the most severe diffuse liver diseases is chronic viral hepatitis C (CHC) combined with non-alcoholic fatty liver disease (NAFLD). After completing the treatment of CHC with drugs of direct antiviral action, there remains a high risk of further progression of liver fibrosis associated with the presence of comorbid pathology - NAFLD in patients. The above circumstances initiated us to search for new non-drug technologies to treat this category of patients. Purpose of the work: to study the effectiveness of use bentonite suspension in rats with a model of NAFLD and to substantiate the practicality of using bentonite in the complex treatment of CHC patients with concomitant NAFLD. Methods: experimental, anamnestic and clinical, general clinical, biochemical, determination of the HOMA index, leptin and adiponectin levels, ultrasonographic studies of the digestive system, bacteriological examination of feces, statistical methods.Results: According to microscopic examination, bentonite application in animals with the NAFLC model leads to a decrease in liver steatosis, restoration of bile formation and bile secretion, and protein-synthesizing liver function. In the blood, there was a positive dynamics to the restoration of energy-dependent transmembrane ion transport according to the activity of Na+/K+ -ATPase and Mg2+/Ca2+ -ATPase (in the liver tissue) and the balance of the antioxidant system (to restrain malondialdehyde and catalase activity). We examined 40 patients with CHC with concomitant NAFLD, who completed the course of antiviral therapy (AVT) and were divided into two groups. 1 (control) group (20 people) received a basic treatment complex (diet therapy, which corresponded to the Mediterranean diet, a regimen of dosed physical exertion, patients of 2 groups (20 people, the main group) additionally received a preparation based on bentonite clay inside - 10 days (1 dose three times a day) Evaluation of the effectiveness of treatment was carried out one month after the start of treatment. Conclusion: The treatment carried out in both groups was accompanied by positive dynamics in most of the diseaseʹs symptoms. But a significant advantage was observed in the second group, where the normalization of cholestatic and dyslipidemic syndromes was established, that is, the effect on the pathogenetic links of the progression of NAFLD was proved. The results obtained confirm the practicality of using the drug with bentonite in the complex treatment of CHC patients with concomitant NAFLD. Keywords: chronic viral hepatitis C, non-alcoholic fatty liver disease, bentonite clay,

Резистентность Helicobacter pylori к кларитромицину в Российской Федерации

Purpose – the systematization of data on the resistance of Helicobacter pylori to clarithromycin in the Russian Federation. Material and methods. Necessary investigations were searched in the electronic databases MEDLINE/PubMed, EMBASE, Cochrane, and the Russian Science Citation Index (RSCI), published between January and September, 2020. The final analysis included original publications from periodically reviewed foreign and Russian publications, as well as dissertations that used validated H. pylori resistance assessment tests with detailed descriptive statistics that allow the resulting data to be included in the meta-analysis. Results. The final analysis included 16 studies (1227 isolates). The generalized indicator of H. pylori resistance to clarithromycin in the Russian Federation was 11.85% (95% confidence interval (CI) 7.315–17.302; I2 = 86.19%). When analyzing papers published over the past ten years, H. pylori resistance to clarithromycin was 10.39% (95% CI 7.103–14.219; I2 = 61.29%). In Moscow and the Moscow Region, the generalized indicator of H. pylori resistance to clarithromycin was 10.87% (95% CI 7,280–15,439; I2 = 50.57%), in St. Petersburg – 22.26% (95% CI 9,525–38,470; I2 = 84.75%), Smolensk – 5.74% (95% CI 3,511–8,789; I2 = 0.00%), Kazan – 10.0% (95% CI 5,023–17,355; I2 = 45.22%). Conclusion. The results show that the resistance of H. pylori to clarithromycin in Russia does not exceed the 15% threshold regulated by the Maastricht-V Consensus, which allows us to consider a triple regimen of anti-Helicobacter therapy with clarithromycin as a first-line therapy. At the same time, to achieve the maximum effect when using classical triple therapy and to level the risk of further progression of clarithromycin resistance of H. pylori in Russia, it is advisable to use methods of its optimization.

Late Presentation of Penetrating Ulcers at the Ascending Aorta Associated With Intra-Mural Haematoma

The combined pathology of intra-mural haematoma (IMH) and penetrating aortic ulcer (PAU) represents disease progression of the PAU with high risk for further progression to either rupture or pseudo-aneurysm formation, and hence surgical intervention should be offered once diagnosis is made regardless of the presentation. We present a 70-year-old fit lady with chronic type A IMH associated with multiple PAUs, diagnosed incidentally, the patient underwent urgent surgical repair with good outcome.

Prevalence of Myopia among Children Attending Pediatrics Ophthalmology Clinic at Ohud Hospital, Medina, Saudi Arabia.

Introduction Around half of the visually impaired population has uncorrected refractive errors (URE), and myopia constitutes a high proportion of them. URE should be screened and treated early to prevent long-term complications. The aim of this study was to determine the prevalence of myopia among all patients attending a pediatric outpatient clinic at Ohud Hospital in Medina, Saudi Arabia (KSA). Method This study was conducted using a convenience sample of all patients attending the clinic (1500 patients) aged between 3 and 14 years, and they were enrolled in the study during the period from May 2017 until September 2017. Result Of 1215 subjects, only 43 (3.54%) were diagnosed with myopia. Out of the study participants, 56.8% were female and the mean age was 9.7 ± 3.6. Myopia was more prevalent in male participants than female participants (n = 525, 4%, n = 690, 3.1%, p=0.5). Low myopia was the most common form among the screened individuals. The level of myopia was associated with the degree of the strabismus angle. Approximately 22% of patients with myopia had >25° strabismus angle. There was a statistically significant association with both near work indoor and outdoor activities on weekends and the level of myopia. Conclusion The prevalence of myopia among pediatrics patients in Medina is 3.54%. We hope that the results of this study will contribute to a better understanding of this public health issue in Saudi Arabia in order to implant a strict screening program for early detection and interventions to reduce the risk of further progression of visual impairment.

Antibiotic-driven escape of host in a parasite-induced Red Queen dynamics.

Winnerless coevolution of hosts and parasites could exhibit Red Queen dynamics, which is characterized by parasite-driven cyclic switching of expressed host phenotypes. We hypothesize that the application of antibiotics to suppress the reproduction of parasites can provide an opportunity for the hosts to escape such winnerless coevolution. Here, we formulate a minimal mathematical model of host–parasite interaction involving multiple host phenotypes that are targeted by adapting parasites. Our model predicts the levels of antibiotic effectiveness that can steer the parasite-driven cyclic switching of host phenotypes (oscillations) to a stable equilibrium of host survival. Our simulations show that uninterrupted application of antibiotic with high-level effectiveness (greater than 85%) is needed to escape the Red Queen dynamics. Interrupted and low level of antibiotic effectiveness are indeed useless to stop host–parasite coevolution. This study can be a guide in designing good practices and protocols to minimize the risk of further progression of parasitic infections.

Interleukin-6 and interleukin-10 gene polymorphisms and the risk of further periodontal disease progression.

Susceptible genotypes to periodontal disease are associated with disease onset and progression. The aim of this study was to examine the effect of gene polymorphisms on the risk of further disease progression and the need for further treatment among adults with chronic periodontal disease. Sixty-seven patients diagnosed with chronic periodontitis were grouped according to genotype status and risk of further progression of disease and tooth loss. All individuals were clinically evaluated for probing pocket depth, clinical attachment loss and bleeding on probing at baseline and 45 days after treatment. Blood samples were collected at baseline and genotyping of the polymorphisms in IL-6 (rs1800796) and IL-10 (rs1800872) genes were performed by PCR. Following DNA separation and genotyping, 65.7% of the patients were homozygous carriers of the IL-6 -572G and 49.3% were carriers of the IL-10 -592A allele. Individuals at risk of disease progression ranged from 7.5% to 62.7% based on the criteria used. Carriers of the IL-10 -592A allele were significantly associated with BOP ≥ 30% and therefore exhibited a higher risk of further periodontal breakdown (p = 0.018) with an odds ratio of 1.18. None of the other definitions of disease progression were significantly associated with the examined IL-6 and IL-10 genotypes (p > 0.05). IL-10 polymorphism was associated with an increased risk of further disease progression and the potential need for further treatment following non-surgical periodontal treatment. Susceptible IL-6 genotypes were not associated with the risk of persisting or recurrent disease activity.