Independent Variables for Determining the Cumulative Live Birth Rates of Aged Patients with Polycystic Ovary Syndrome or Tubal Factor Infertility: A Retrospective Cohort Study

ObjectiveTo assess whether women of advanced age (≥35 years) with polycystic ovary syndrome (PCOS) have the same cumulative live birth rate (CLBR) as their age-matched controls with tubal factor infertility and to determine the influencing factors on the CLBRs of aged women.DesignA retrospective cohort study.Setting and PopulationA total of 160 women of advanced age (≥35 years) with PCOS and 1073 women with tubal factor infertility were included in our study. All patients underwent their first fresh cycles and subsequent frozen cycles within in one year in our centre from 2015 to 2020.MethodsTo determine independent influencing factors on the CLBRs of these aged patients, a multivariable Cox regression model of CLBR according to the transfer cycle type was constructed. Main outcome measure(s): CLBRs.ResultThe Cox regression model of the CLBRs indicated that there was no significant difference between the PCOS group and the tubal infertility group in terms of advanced age (HR, 0.95; 95% CI, 0.71-1.27, P=0.732). The CLBR significantly decreased for women of advanced reproductive age up to 37 years of age (HR, 0.46; 95% CI, 0.39-0.56, P<0.001). The CLBR increased by 63% when more than ten oocytes were retrieved (HR, 1.63; 95% CI, 1.34-1.98, P<0.001). Patients with an AMH level above 32.13pmol/l were likely to have a 72%(HR, 1.72; 95% CI, 1.08-2.73, = 0.023) and 34% (HR, 1.34; 95% CI, 1.07-1.68, P=0.010)improvement in CLBR compared to those with an AMH below 7.85pmol/l and 7.85-32.12pmol/l, respectively.ConclusionDespite the higher number of oocytes retrieved in PCOS patients, the reproductive window is not extended for PCOS patients compared with tubal factor infertility patients. Age, AMH and the number of oocytes retrieved play crucial roles in the CLBRs of patients of advanced age (≥35 years).

Investigating the genomic alteration improved the clinical outcome of aged patients with lung carcinoma

Background Lung carcinoma is a common geriatric disease. The development of genotype-targeted therapies greatly improved the management of lung carcinoma. However, the treatment for old patients can be more complex than that for young individuals. Results To investigate the benefits of genetic detection for older patients with lung carcinoma, we explored the genomic profiling of 258 patients with more than 55 years using a targeted next generation sequencing, and some of these patients were treated with targeted therapies based on the results of genomic detection. KRAS codon 61 mutations were found in 15.2% KRAS-mutated patients, which tend to be co-existing with other classical activating mutations other than codons 12/13. Acquired EGFR C797S mutations were identified in 2 cases and ERBB2 amplification was identified in 1 case. All these 3 cases developed resistance to EGFR tyrosine kinase inhibitors and showed expected results of their followed therapies. The median progression-free survival and median overall survival of patients treated with molecular targeted therapies were better than those of patients treated with chemoradiotherapy alone. Conclusions Our findings revealed the specific genomic profiles of patients older than 55 years with lung carcinoma and suggested that these old patients have been benefit from the genetic detection, which helped identify druggable mutations and distinguish resistance mechanisms.

Role of open access echocardiography in detection of cardiac structural and functional abnormalities

PurposeTo evaluate the prevalence and incidence of significant structural heart disease in targeted patients with cardiac symptoms referred by general practitioners (GPs) using open access echocardiography, without prior clinical evaluation by a cardiologist.DesignData were derived from 488 subjects who underwent transthoracic echocardiography between January and April 2018. Patients were referred directly by GPs in East Berkshire, South England, through an online platform. Echocardiography was performed within 4–6 weeks of referral and all reports were assessed by a consultant cardiologist with expedited follow-up facilitated pro re nata. Results were analysed to determine the frequency of detection of structural abnormalities, particularly of the left ventricle and cardiac valves.ResultsEchocardiography was prospectively performed in consecutive subjects (50% male, mean (±SD) age 68.5±22 years; 50% female; mean (±SD) 64.6 (±19.1)). At least one abnormality likely to change management was found in 133 (27.3%) of all open access echocardiograms. Clinical heart failure with left ventricular systolic dysfunction (LVSD) and diastolic dysfunction was confirmed in 46 (9%) and 69 (14%), respectively. Of the 46 patients with LVSD, 33 were new diagnoses. Significant cardiac valve disease was found in 42 (8.6%) patients. 12 of these had known valvular disease or previous valvular surgery, and 30 were new diagnoses.ConclusionMajor structural and functional cardiac abnormalities are common in late middle-aged patients who present to GPs with cardiac symptoms and signs. Reported, unrestricted open access echocardiography enables early detection of significant cardiac pathology and timely intervention may improve cardiovascular outcomes.

Age-associated features of the development of fibrosis and inflamaging in patients with arterial hypertension and ischemic stroke

В статье рассмотрены вопросы развития фиброза и иммунного воспаления у больных артериальной гипертензией (АГ) с острым ишемическим инсультом (ИИ) в пожилом возрасте. Цель исследования - изучение возраст-ассоциированных особенностей концентрации маркеров фиброза (металлопротеиназы-9, тканевого ингибитора матриксных металлопротеиназ-1, их соотношения ММП-9/ТИМП-1), иммунного воспаления (TNF-α, IL-1β, INF-γ) у больных АГ с ИИ. В исследование были включены 86 больных АГ II степени, из которых 42 человека - среднего возраста (53±5 лет) и 44 - пожилого (66±5 лет), контрольную группу составили 22 пациента пожилого возраста с АГ без ИИ в анамнезе. Критерии включения - пациенты с АГ, поступившие в стационар в остром периоде первого церебрального инсульта. Установлено, что у пожилых больных АГ с ИИ показатели инфламэйджинга и маркеры фиброза были достоверно выше, чем у лиц среднего возраста. Уровень IL-1β был выше на 31,7 % (р<0,01), TNF-α - на 55,7 % (р<0,001), INF-γ - на 36,6 % (р<0,01), уровень ММП-9 - на 46,4 % (р<0,01), ТИМП-1 - на 21,2 % (р<0,01), ММП-9/ТИМП-1 - на 19,6 % (р<0,01) в пожилом возрасте по сравнению с больными среднего возраста с АГ и острым ИИ. Таким образом, установлено, что больные АГ с ИИ имеют нарушения процессов инфламейджинга, синтеза и деградации внеклеточного матрикса, особенно выраженные в пожилом возрасте. The article deals with the development of fibrosis and immune inflammation in patients with arterial hypertension and acute ischemic stroke in old age. The aim of the study was to study age-associated features of the concentration of fibrosis markers (metalloproteinase-9, tissue inhibitor of matrix metalloproteinases-1, their ratio MMP-9/TIMP-1), immune inflammation (TNF-α, IL-1β, INF-γ) in patients with arterial hypertension and ischemic stroke (AI). The study included 86 patients with arterial hypertension (AH) of the 2nd degree, of which 42 were middle-aged (53±5 years) and 44 elderly (66±5 years). The control group consisted of 22 elderly patients with AH without a history of AI. The criteria for inclusion in the study are patients with hypertension who were admitted to the hospital in the acute period of the first cerebral stroke. It was found that in elderly patients with hypertension with AI, the indicators of inflamaging and fibrosis markers were significantly higher than in middle-aged people. The level of IL-1β was 31,7 % higher (p<0,01), TNF-α by 55,7 % (p<0,001), INF-γ by 36,6 % (p<0,01), the level of MMP-9 was 46,4 % higher (p<0,01), TIMP-1 by 21,2 % (p<0,01), MMP-9/TIMP-1 by 19,6 % (p<0,01) in the elderly compared to middle-aged patients with hypertension and acute AI. Thus, it was found that patients with arterial hypertension and ischemic stroke have violations of the processes of inflamaging, synthesis and degradation of the extracellular matrix, especially pronounced in old age.

Characteristic of spermogram parameters in men with reproductive pathology in age-related aspect

Introduction. The prevalence of andrological diseases among adolescents and young adults resulting in lowered reproductive potential has been noted to progressively increase. At the same time, the number of couples starting to manage reproductive issues after 35–40 years of age highlighting the onset of male androgen deficiency continues to rise. Therefore, the analysis of spermogram as the key element in assessing male reproductive potential is better to conduct at different age periods of man's life.Aim: to compare spermogram parameters in different age groups of patients with reproductive pathology.Materials and Мethods. The analysis of spermograms in adolescents with left-sided grade II–III varicocele aged 17 years and in infertile males aged 22–48 years was performed. Semen analysis was conducted in accordance with the standards of the 5 th edition of the World Health Organization and included the following parameters: semen volume (ml), sperm concentration (million/ml), total sperm count (million), acidity, viscosity, progressive motility, total motility, viability, morphology, detected mucus, leukocytes, amyloid bodies, lecithin grains as well as sperm aggregation and agglutination. The stained preparations were used to assess the morphology of spermatozoa and spermatogenesis cells. According to the spermogram data obtained, the following conclusions were drawn: normozoospermia, oligozoospermia, asthenozoospermia, teratozoospermia. Statistical analysis was performed by using Statistica 10.0 software (StatSoft Inc., USA). The normality distribution was assessed using the χ2 test. Quantitative parameters were presented as arithmetic means and standard deviations (M ± SD). Assessing significance of differences was performed by using the Student's t-test, whereas inter-parameter correlation relations were analyzed by using the linear Pearson's correlation coefficient. A significance level between inter-group parameters was set at p < 0.05.Results. It was found that adolescents with varicocele vs. adult men had significantly decreased ejaculate volume. In particular, the average ejaculate volume in adolescents and adult men was 2.32 ± 1.22 ml and 3.50 ± 1.44 ml, respectively, so that the larger number of young patients were noted to have ejaculate volume below 1.5 ml. Compared to young subjects, aged patients had decreased sperm concentration (35.88 ± 25.74 versus 72.20 ± 49.32 million/ml) and total sperm count (120.58 ± 91.72 versus 173.07 ± 163.92 million). Young patients were found to have significantly superior data in all categories of sperm motility, whereas infertile men were diagnosed with impaired sperm motility. In particular, adolescents were featured with the average number of spermatozoa displaying fast and slow translational movement comprising 17.12 ± 11.04 % and 29.30 ± 12.29 %, respectively, the proportion of progressive motility spermatozoa was 46.20 ± 19.82 %. In contrast, similar parameters in adult men were 5.10 ± 6.36 %, 19.80 ± 9.61 %, and 24.95 ± 11.23 %, respectively. In infertile men prevalence of lacked spermatozoa with rapid forward movement was 46 (46.0 %), in adolescents – 8 (8.6%), whereas rate of immotile spermatozoa in infertile men, on average, accounted for 53.10 ± 14.56 %, in adolescents – 34.40 ± 21.83 %. In addition, adolescents with varicocele had significantly fewer spermatozoa with normal morphology – 14.14 ± 8.06 % (in adult men – 30.08 ± 17.94 %), there were more abundant defects in the sperm head – 58.01 ± 12.43 % (in men – 48.83 ± 18.95 %) and flagella – 17.24 ± 6.31 % (in men – 10.29 ± 6.21 %). The data obtained showed that adolescents were more often diagnosed with normozoospermia – in 49 (52.7 %) cases, in infertile men – in 12 (12.0 %) cases, whereas in aged men asthenozoospermia was detected in 82 (82.0 %) cases, in adolescents – 5 (5.4 %) cases.Conclusion. The abnormalities in the spermogram revealed in adolescents may be associated with unestablished spermatogenesis. Normozoospermia more common in adolescents with varicocele may evidence about preserved reproductive potential. Impaired sperm motility in aged patients seems to be related to the formation of oxidative stress and damage to spermatozoa by reactive oxygen species due to combined age-related changes, cumulation of the negative effects of environmental and lifestyle factors, as well as comorbidities.

Effects of acceptance and commitment therapy on self-management skills and psychological resilience of young and middle-aged patients underwent percutaneous transluminal coronary intervention for primary myocardial infarction: a pilot study

Background Acceptance and commitment therapy (ACT) is an intervention focusing on altering how patients relate to their thoughts. This study aimed to investigate the effects of ACT on self-management ability and psychological resilience of young and middle-aged patients undergoing percutaneous transluminal coronary intervention (PCI) for primary myocardial infarction (MI). Methods This pilot study included 98 young and middle-aged patients who underwent PCI for primary MI using a convenient sampling method. The patients were divided into a control group and an ACT group using the random number table method. The patients in the control group received routine nursing, while those in the ACT group received routine nursing combined with ACT. Results The psychological resilience and self-management ability scores were significantly higher in the ACT group than in the control group 3 months after the intervention (P < 0.001 and < 0.05, respectively). In addition, compared to the baseline scores of psychological resilience and self-management ability, these scores were significantly higher in the ACT group at 3 months post-intervention (P < 0.001 and < 0.05, respectively). Conclusion ACT could enhance the psychological resilience and self-efficacy and improve the self-management ability of young and middle-aged patients who underwent PCI for primary MI. Trial registration China Clinical Trial Center ChiCTR2000029775. Registered on 13 February 2020. Registration title:Study on the popularization and application of rotational atherectomy for the treatment of severely calcified coronary lesions.

Blood microflora of patients with atherosclerotic vascular lesions and microflora of atherosclerotic plaques of carotid arteries

Aim of the study was to assess the frequency of microflora detection in the blood of patients with atherosclerotic vascular lesions and middle-aged patients without clinical symptoms of atherosclerosis. Compare the nature of microflora isolated from blood and the range of microorganisms isolated from atherosclerotic plaques (AP) of patients with carotid arteries atherosclerosis. Material and methods. The hemocultures of 118 men and 33 women with atherosclerosis (mean age 55.6 years) as well as 10 blood samples of 3 men and 7 women formed into a control group (mean age 37 years) were examined. Test samples were cultivated for 6 months. Tissue platings of carotid arteries AP in 11 women and 24 men of the main group (mean age 58.0) were incubated for 2 months. Methods based on Student’s t-test and Mann-Whitney U-test were used for statistical analysis of the obtained results. Results. Propionibacterium acnes hemocultures were detected in 9.9 % of patients from the main and control groups. In blood Staphylococcus epidermidis and Stenotrophomonas maltophylia were detected in 0.7 % of samples. P. acnes and Staphylococcus spp. cultures were obtained from AP in 34.3 and 45.7 %, including both microorganisms in 8.6 % of samples. Conclusions. P. acnes cultures are found equally frequently in the blood of atherosclerotic patients and patients not yet diagnosed with atherosclerosis. This study confirmed the presence of the same-name microorganisms in blood and atherosclerotic plaques. In 5.7 % (2 of 35) it was possible to extract simultaneously a P. acnes culture from two loci (atherosclerotic tissue and blood) in specific individuals. Further detailed research is required to study the etiological significance of the microbial factor in the atherosclerotic plaque formation.

Incidence and risk factors associated with preoperative deep venous thrombosis in the young and middle-aged patients after hip fracture

Objective This study aims to investigate the incidence, occurrence timing and locations of preoperative DVT and identify the associated factors in this group. Methods A retrospective analysis of collected data in young and middle-aged (18–59 years) patients who presented with hip fracture between October 2015 and December 2018 was conducted. Before operation, patients were routinely examined for DVT by Duplex ultrasonography (DUS). Electronic medical records were retrieved to collect the data, involving demographics, comorbidities, injury and laboratory biomarkers after admission. Multivariate logistic regression analysis was performed to identify factors that were independently associated with DVT. Results Eight hundred and fifty-seven patients were included, and 51 (6.0%) were diagnosed with preoperative DVT, with 2.5% for proximal DVT. The average age of patients with DVT is 48.7 ± 9.4 year, while that of patients without DVT is 45.0 ± 10.9 year. The mean time from injury to diagnosis of DVT was 6.8 ± 5.5 days, 43.1% cases occurring at day 2–4 after injury. Among 51 patients with DVT, 97 thrombi were found. Most patients had thrombi at injured extremity (72.5%), 19.6% at uninjured and 7.8% at bilateral extremities. There are significantly difference between patients with DVT and patients without DVT in term of prevalence of total protein (41.2% vs 24.4%, P = 0.008), albumin (54.9% vs 25.6%, P = 0.001), low lactate dehydrogenase (51.0% vs 30.3%, P = 0.002), lower serum sodium concentration (60.8% vs 29.9%, P = 0.001), lower RBC count (68.6% vs 37.0%, P = 0.001), lower HGB (51.0% vs 35.1%, P = 0.022), higher HCT (86.3% vs 35.1%, P = 0.022) and higher platelet count (37.3% vs 11.3%, P = 0.001). The multivariate analyses showed increasing age in year (OR 1.04, 95% CI; P = 0.020), delay to DUS (OR, 1.26; P = 0.001), abnormal LDH (OR, 1.45; P = 0.026), lower serum sodium concentration (OR, 2.56; P = 0.007), and higher HCT level (OR, 4.11; P = 0.003) were independently associated with DVT. Conclusion These findings could be beneficial in informed preventive of DVT and optimized management of hip fracture in specific group of young and mid-aged patients.

Caudal epidural blockades for chronic pain in the lower back in working age

Introduction. Chronic back pain syndrome, which significantly restricts a person’s daily activity, can cause the formation of depressive states and is a significantly more difficult task for treatment compared to acute pain.Aim. To evaluate the efficacy and safety of caudal epidural catheterization (CEC) and local therapy with anesthetics and glucocorticoids for chronic nonspecific discogenic and chronic radicular low back pain (LBP) in young and middle-aged patients.Materials and methods. 42 patients aged from 29 to 59 years, who in the neurosurgical department of the Vologda City Hospital No. 1 in 2017–2019 underwent an operation to install a caudal epidural catheter and prolonged injection therapy of local anesthetics and glucocorticosteroids for chronic nonspecific discogenic and chronic radicular LBP.Results. There were no purulent-septic complications, hematomas of the spinal canal. In the group of patients with radicular syndrome the average values of LBP according to VAS were as follows: before CEC – 78.5 mm; 5 days after CEC – 24.1 mm; 6 months after CEC – 19.6 mm; after 12 months – 17.9 mm. In the group of patients with nonspecific discogenic LBP the average pain estimates for VAS were as follows: before CEC – 78.1 mm; 5 days after CEC – 21.7 mm; 6 months after CEC – 20.9 mm; after 12 months – 23.4 mm.Сonclusion. Our experience indicates a high long-term efficacy and safety of treatment with caudal epidural catheterization and local prolonged therapy with anesthetics and glucocorticoids for chronic radicular and chronic nonspecific discogenic pain in the lower back in young and middle-aged patients selected on the basis of a special system of criteria.

Cholinergic blockade of neuroinflammation – from tissue to RNA regulators

Inflammatory stimuli and consequent pro-inflammatory immune responses may facilitate neurodegeneration and threaten survival following pathogen infection or trauma, but potential controllers preventing these risks are incompletely understood. Here, we argue that small RNA regulators of acetylcholine (ACh) signaling, including microRNAs and transfer RNA fragments may tilt the balance between innate and adaptive immunity, avoid chronic inflammation and prevent the neuroinflammation-mediated exacerbation of many neurological diseases. While the restrictive permeability of the blood-brain barrier protects the brain from peripheral immune events, this barrier can be disrupted by inflammation and is weakened with age. The consequently dysregulated balance between pro- and anti-inflammatory processes may modify the immune activities of brain microglia, astrocytes, perivascular macrophages, oligodendrocytes and dendritic cells, leading to neuronal damage. Notably, the vagus nerve mediates the peripheral cholinergic anti-inflammatory reflex and underlines the consistent control of body-brain inflammation by pro-inflammatory cytokines, which affect cholinergic functions; therefore, the disruption of this reflex can exacerbate cognitive impairments such as attention deficits and delirium. RNA regulators can contribute to re-balancing the cholinergic network and avoiding its chronic deterioration, and their activities may differ between men and women and/or wear off with age. This can lead to hypersensitivity of aged patients to inflammation and higher risks of neuroinflammatory-driven cholinergic impairments such as delirium and dementia following COVID-19 infection. The age- and sex-driven differences in post-transcriptional RNA regulators of cholinergic elements may hence indicate new personalized therapeutic options for neuroinflammatory diseases.