The Trajectory of Successful Aging: Insights from Metagenome and Cytokine Profiling.

INTRODUCTION: The longevity is influenced by genetic, environmental, and lifestyle factors. The specific changes that occur in the gut microbiome during the aging process, and their relationship to longevity and immune function, have not yet been fully understood. The ongoing research of other microbiome based on longevity cohort in Kazakhstan provides preliminary information on longevity-related aging, where cytokine expression is associated with specific microbial communities and microbial functions. METHODS: Metagenomic shotgun sequencing study of 40 long-lived individuals aged 90 years and over was carried out, who were conditionally healthy and active, able to serve themselves, without a history of serious infection and cancer, who had not taken any antimicrobials, including probiotics. Blood serum was analyzed for clinical and laboratory characteristics. The cytokine and chemokine profile in serum and stool samples was assessed using multiplex analysis. RESULTS: We found a significant increase in the expression of pro-inflammatory cytokines IL-1a, IL-6, 12p70, IP-10, IFNα2, IL-15, TNFa, as well as chemokines MIP-1a/CCL3 and MIP-1b/CCL4, chemokine motif ligands MCP-3/CCL7 and MDC/CCL22(1c). Nonagenerians and centenarians demonstrated a greater diversity of core microbiota genera and showed an elevated prevalence of the genera Bacteroides, Clostridium, Escherichia, and Alistipes. Conversely, there was a decrease in the abundance of the genera Ruminococcus, Fusicatenibacter, Dorea, as well as the species Fusicatenibacter saccharivorans. Furthermore, functional analysis revealed that the microbiome in long-lived group has a high capacity for lipid metabolism, amino acid degradation, and potential signs of chronic inflammatory status. CONCLUSION: Long-lived individuals exhibit an immune system imbalance and observed changes in the composition of the gut microbiota at the genus level between to the two age-groups. Age-related changes in the gut microbiome, metabolic functions of the microbial community, and chronic inflammation all contribute to immunosenescence. In turn, the inflammatory state and microbial composition of the gut is related to nutritional status.

The surgical management of penile oleogranuloma: case series.

Oleogranuloma of the penis is a complex set of pathological processes caused by the injection of a foreign substance (gel, balls, rods, etc.) into the penis with the purpose of penile augmentation. In this case series, we investigated a variety of clinical presentations of oleogranuloma and described our experience in managing the complications. We analyzed data on 18 patients with penile self-injections admitted to the hospitals of Astana City, Kazakhstan, during an 11-year period. The mean age of patients at admittance was 37.4 ± 6.4 years. The most common substance of injection was Vaseline (n = 16, 88.9%). The mean interval between the time of injection and the first presentation to the hospital was 10.8 ± 6.5 years. Complications included necrosis (n = 13, 72.2%), pain or swelling (n = 6, 33.3%) and cosmetic dissatisfaction (n = 5, 27.8%). All patients received surgical treatment (n = 18, 100%): simple excision with primary closure was performed for one-half of the patients (n = 9, 50%), while another half of patients underwent the two-stage scrotum skin flap surgery (n = 9, 50%). The findings of this study should raise the awareness about the diverse clinical presentations of penile self-injections among physicians for early diagnosis and timely management.

Epidemiology of Lung Cancer in Kazakhstan: Trends and Geographic Distribution.

OBJECTIVE: The aim is to study the trends of lung cancer (LC) incidence in the regional context in Kazakhstan. METHODS: The retrospective study was done using descriptive and analytical methods of oncoepidemiology. The extensive, crude and age-specific incidence rates are determined according to the generally accepted methodology used in sanitary statistics. The data were used to calculate the average percentage change (APС) using the Joinpoint regression analysis to determine the trend over the study period. RESULTS: Over the 10 years under study, 36,916 new cases of LC were registered in the country (80.5% - in men and 19.5% - in women). During the studied years the average age of patients was 64.2±0.1 years (95%CI=63.9-64.4). The highest incidence rates per 100,000 in the entire population were found in the age groups 65-69 years (147.6±2.7), 70-74 years (159.3±2.5), and 75-79 years (147.1±3.2). The incidence of LC tended to increase only at the age of 80-84 years (APC=+1.26) and the most pronounced average annual decline rates were observed in the age groups of 45-49 years (APC=-4.09), 50-54 years (APC=-4.20) and 85+ years (APC=-4.07). The average annual standardized incidence rate was 22.2 per 100,000, and in dynamics tended to decrease (APC=-2.04). There is a decrease in incidence in almost all regions, with the exception of the Mangystau region (APC=+1.65). During the compilation of cartograms, incidence rates were determined on the basis of standardized indicators: low - up to 20.6, average - from 20.6 to 25.6, high - above 25.6 per 100,000 for the entire population. CONCLUSION: The incidence of lung cancer in Kazakhstan is decreasing. The incidence among the male population is six times higher than among the female, while the rate of decline is more pronounced. The incidence tends to decrease in almost all regions. High rates were found in the northern and eastern regions.

Comparison of Technical Success and Adverse Events of Plaque Incision and Grafting Methods in Patients with Peyronie's disease: Tunica Vaginalis versus Buccal Mucosa.

OBJECTIVE: To compare the clinical outcomes of Peyronie's disease (PD) patients who were treated by plaque incision and grafting either with tunica vaginalis (TV) or buccal mucosa (BM) grafts. METHODS: PD patients in BM (n=20) and TV group (n = 20) were recruited between 2013 and 2020. Erectile dysfunction was assessed by short form of International Index of Erectile Function Questionnaire (IIEF-5). Technical success was defined as residual curvature ≤15°. Penile Doppler ultrasound was performed at baseline evaluation, 3-, and 24 months. Peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistance index were measured in erect penis. Erect penile length and curvature angle were measured at baseline and at 3, 12, and 24 months. RESULTS: Mean age of the groups was comparable (47.2 ± 10.8 years in TV vs 46.5 ± 9.9 years in BM groups). Baseline mean penile curvature was 48.0 ± 6.6° (TV) and 50.3±11.6° (BM) (P <.001). Mean residual curvature at 24-month visits was 12.4 ± 4.9° (TV) and 7.9 ± 3.7° (BM), not significantly different. Technical success rate was 90% for both groups at 24 months. Surgery significantly increased erect penile length in both groups. Mean preoperative IIEF-5 scores were 18.4 ± 2.5 and 17.5 ± 2.2 in TV and BM groups, respectively. In both groups, IIEF-5 scores significantly improved after surgery with no intergroup IIEF-5 difference (20.6 ± 2.6 in TV and 21.3 ± 2.2 in BM). Mean postoperative PSV significantly increased, EDV significantly decreased in both groups, however, there was no significant intergroup difference. CONCLUSION: Both grafting materials provided similar beneficial effects regarding technical success, erectile dysfunction, and penile length.

Autologous testicular tunica vaginalis graft in Peyronie's disease: a prospective evaluation.

BACKGROUND: Peyronie's disease (PD) is a two-phase progressive condition characterized by inelastic plaques in the tunica albuginea of the penis, leading to curvature of the penis. Men with PD also suffer from psychological distress, and sexual life and overall quality of life. Although the preferred surgical treatment modality in Peyronie's disease is plaque incision and grafting, there is lack of studies assessing the erectile function and penile vasculature after the treatment. OBJECTIVES: We aimed to evaluate the efficiency and safety of plaque incision and tunica vaginalis of testis grafting in PD. METHODS: This was a prospective analysis. Erectile dysfunction was assessed via International Index of Erectile Function Questionnaire (IIEF-5). Penile Doppler ultrasound was performed to assess peak systolic velocity (PSV) and end-diastolic velocity (EDV). Postoperative follow-ups were scheduled at 3, 12, and 24 months. RESULTS: Twenty patients (mean age 47.2 ± 10.8 years) were included. The mean preoperative penile curvature was 48 ± 6.6°. The technical success rate was 100% at 3 months and 90% at 24 months. At follow-up visits, mean erect penile length was no different from the baseline. The baseline mean IIEF-5 score was 18.4 ± 2.5. The mean IIEF-5 score was 20.6 ± 2.6 at 24-month visit (p < 0.0001). Mean PSV significantly increased, while EDV significantly reduced after surgery. There were no serious complications related to surgery. CONCLUSIONS: We conclude that surgical reconstruction of penile curvature with tunica vaginalis grafting was a safe and effective procedure in PD.

Inflammatory Biomarkers as Predictors of Infected Diabetic Foot Ulcer.

Diabetic foot ulcer infection is a crucial complication associated with lower-limb amputation and postoperative mortality in individuals with diabetes mellitus. Deciding if a diabetic foot ulcer is infected in a community setting is challenging without validated point-of-care tests. Early detection of infected diabetic foot ulcers can reduce the frequency of hospitalizations, the occurrence of disability, and chances of mortality. Inflammatory biomarkers are predictors of infected diabetic foot ulcers and lower-limb amputation. Procalcitonin, CRP, pentraxin-3, interleukin-6, and calprotectin may help distinguish uninfected from mildly infected diabetic foot ulcers and diagnose soft tissue infections, bone lesions, and sepsis in diabetic patients. Moreover, these biomarkers may be predictors of lower-limb amputation and postoperative mortality. The current management of infected diabetic foot ulcers is disappointing and unsatisfactory, both in preventing its development and halting and modifying its progression. The use of new (molecular) techniques for the identification of the IDFU has not yet to be proven superior to classic cultural techniques for the management of such patients. For clinicians, if the risk stratification of DFU can be obtained earlier in diabetic patients, the hospitalization, disability, and mortality rate will be reduced. For the practical application of these biomarkers, it is important to correlate these quantitative parameters with clinical symptoms. Based on clinical observations and inflammatory biomarker evaluation, it can be used to guide clinical treatment methods. This review details clinical information published during the past several decades and discusses inflammatory biomarkers that may determine the risk and level of infection of diabetic foot ulcers.

Trends of Colorectal Cancer Incidence in Kazakhstan.

AAMC: Background and objective: Colorectal cancer (CRC) remains one of the most widespread human malignancies. The aim of this study was to study trends of the incidence of CRC in Kazakhstan. Materials and Method: This retrospective study was done using descriptive and analytical methods of oncoepidemiology. Results: During the study period from 2009 to 2018, 28,950 new cases of CRC were recorded, 13,779 (47.6%) cases were allocated to men and 15,171 (52.4%) to women. It was found that the incidence rate of CRC increased from 14.79 (2009) to 17.72 in 2018 and the overall growth was 2.93 cases per 100,000. This increase was due to the age structure ­ ΣΔA=+1.42, the risk of acquiring illness ­ ΣΔR=+1.31, and their combined effect ­ ΣΔRA=+0.20. The component analysis results revealed that the increase in the number of patients with CRC was mainly due to the growth of the population (ΔP=+37.7%), changes in age structure (ΔA=+26.6%), and changes associated with the risk of acquiring illness (ΔR=+24.6%). The number of patients (both sexes) was increasing in many regions largely due to the influence of the age structure of the population. In addition, it was found that growth in the number of patients in most regions, both men and women, was associated primarily with the risk of acquiring illness. Conclusion: The findings of the current study showed increasing trends in the incidence of CRC in all regions of the country. These changes were mainly influenced by demographic factors (population size and age structure), risk of acquiring the disease, and their combined effect.^ieng

Impact of Screening on Breast Cancer Incidence in Kazakhstan: Results of Component Analysis.

OBJECTIVE: The study is to conduct a component analysis of the dynamics of the incidence of BC (BC) in Kazakhstan, taking into account regions. METHODS: Primary data were for registered patients with BC (ICD 10 - C50) in the whole country during the period of 2009-2018. Evaluation of changes in BC incidence in the population of Kazakhstan was performed using component analysis according to the methodological recommendations. RESULTS: The study period, 40,199 new cases of BC were recorded. The incidence rate increased from 39.5 (2009) to 49.6 in 2018 and the overall growth was 2.8 per 100,000 population of female, including due to the age structure - ∑ΔA=+2.99, due to the risk of acquiring illness - ∑ΔR=+6.82 and their combined effect - ∑ΔRA=+0.31. The component analysis revealed that the increase in the number of patients with BC was mainly due to the growth of the population (ΔP=+31.1%), changes in its age structure (ΔA=+18.0%) and changes associated with the risk of acquiring illness (ΔR=+41.0%). The increase in the number of patients in the regions of the republic is associated with the influence of demographic factors and with risk factors for getting sick, including mammographic screening. CONCLUSION: Thus, as a result of the component analysis, the role of the influence of demographic factors and the risk of acquiring illness on the formation of the number of patients and the incidence of BC was evaluated, while geographical variability was established. This research was the first epidemiological study of the dynamics of BC in the regional context by the method of component analysis in the population of Kazakhstan. The implementation of the results of this study is recommended in management of anticancer activities for BC.

New Trends of Cervical Cancer Incidence in Kazakhstan.

OBJECTIVE: The epidemiological features of the cervical cancer (CC) incidence and its spatial and temporal assessment in Kazakhstan were studied. METHODS: The retrospective study was done for the period 2009-2018. Descriptive and analytical methods of oncoepidemiology were used. RESULTS: During the study period, 16,441 new cases of CC were registered. The average annual crude and age-standardized incidence rate were 18.6±0.5 and 17.7±0.4 cases per 100,000 population of female, respectively, and their trends tended to increase (Тup=+2.3%; R2=0.708 and Тup=+1.9%; R2=0.615, respectively). The analysis of ASIR showed unimodal growth with a peak at 50-54 years - 45.3±1.1 cases per 100,000 population of female. Trends of ASIR decreased up to 30 years (Tdown=-1.8%; R2=0.111) and 35-59 years (Tdown=-0.9%; R2=0.103), in other age groups the trends increased, and were most pronounced in 40-44 (Тup=+4.1%; R2=0.878) and 65-69 years (Тup=+4.4%; R2=0.537). Trends in ASR of СС tended to grow in almost all regions, with higher levels in Mangystau (Тup=+4.1%; R2=0.482) and Aktobe (Тup=+6.3%; R2=0.846) regions. The cartograms of ASR per 100,000 population of female were allocated according to the following criteria: low - up to 16.3, average - from 16.3 to 19.2, high - above 19.2. The results of the spatial analysis showed the regions with a higher levels of CC incidence rate per 100,000 population of female: East Kazakhstan (19.8), Aktobe (20.0), Almaty (20.1), Kostanay region (20.9), Atyrau (21.7) regions and Almaty city (22.0). CONCLUSION: The study of trends of the cervical cancer incidence has the theoretical and practical value:  monitoring and evaluation of screening programmes, which are implemented in the country, and conduction of secondary prevention of cervical pathology. Health authorities should consider the obtained results in the in the organization of anti-cancer activities.

Prediction Mortality Rate Due to the Road-Traffic Accidents in Kazakhstan.

BACKGROUND: As a result of the road traffic accidents 1.25 mln. of working-age people die each year on the roads. Frequency of the RTA is 11 times higher in our country than in Europe, that influence on demographic and economic situation in the republic. Creation of the math modeling and prediction of traffic mortality rate in Kazakhstan will allow to develop measure on its decrease. METHODS: Short-term dotted prediction of population mortality level of Kazakhstan was used, in particular - methods of regressive analysis. General prognosis throughout the country up to 2021 was made on the basis of data for 1999-2018. The more relevant method for prediction is exponential function taking into account the features of mortality rate level trend. RESULTS: Prediction of traffic fatalities without division into the age-related groups for 2019 is 2132±181 case with a probability 2/3. Expected levels for 2020-2027 cases, for 2021-1927 cases.Annual mortality decrease rate according to the 0-19 age-related at an average is 6.4% among men and 5.8% among women, according to age group as a whole - by 6.2%; from 20 up to 64 age related group - 5.1 % on all population category; older 65 age -group is by 2.2 %, 3.7 % among men, 2.9% among women as a whole. CONCLUSION: In the foreseeable future the number of traffic deaths in Kazakhstan will tend to decrease at a slower pace. Mortality rates due to road traffic accidents among working-age men will be 3 times higher than women in this age group.