Machine Learning-Based Decision-Making in Geriatrics: Aging Phenotype Calculator and Survival Prognosis.

Aging is a natural process with varying effects. As we grow older, our bodies become more susceptible to aging-associated diseases. These diseases, individually or collectively, lead to the formation of distinct aging phenotypes. Identifying these aging phenotypes and understanding the complex interplay between coexistent diseases would facilitate more personalized patient management, a better prognosis, and a prolonged lifespan. Many studies distinguish between successful aging and frailty. However, this simple distinction fails to reflect the diversity of underlying causes. In this study, we sought to establish the underlying causes of frailty and determine the patterns in which these causes converge to form aging phenotypes. We conducted a comprehensive geriatric examination, cognitive assessment, and survival analysis of 2,688 long-living adults (median age = 92 years). The obtained data were clustered and used as input data for the Aging Phenotype Calculator, a multiclass classification model validated on an independent dataset of 96 older adults. The accuracy of the model was assessed using the receiver operating characteristic curve and the area under the curve. Additionally, we analyzed socioeconomic factors that could contribute to specific aging patterns. We identified five aging phenotypes: non-frailty, multimorbid frailty, metabolic frailty, cognitive frailty, and functional frailty. For each phenotype, we determined the underlying diseases and conditions and assessed the survival rate. Additionally, we provided management recommendations for each of the five phenotypes based on their distinct features and associated challenges. The identified aging phenotypes may facilitate better-informed decision-making. The Aging Phenotype Calculator (ROC AUC = 92%) may greatly assist geriatricians in patient management.

Ageism Among Physicians and Nurses in Russia.

The phenomenon of ageism has been studied extensively in the Western world, but there is only a small number of studies among medical staff in Russia. The aim of this study was to assess the prevalence of ageism and to identify variables that can explain ageism in a sample of physicians and nurses in Russia. This is a prospective cross-sectional study of physicians and nurses who participated in a training course in the years 2016-2018 in Russia. Data collected before the start of training included the Fraboni scale of ageism (FSA) questionnaire, and sociodemographic characteristics including age, gender, profession, professional seniority, place of work, and number of older adults treated by the study participant over the past half year. In total, 903 physicians and nurses participated in the study. The mean FSA score was 2.75 ± 0.49, which indicates a moderate degree of ageism. There was a trend to higher scores among nurses compared with physicians (2.78 ± 0.50 vs. 2.76 ± 0.48, p < 0.465). There was a weak, but statistically significant, correlation between ageism and age (r = 0.157, p < 0.0001), professional seniority (r = 0.098, p < 0.003), and the number of older adult patients treated by the participant over the prior half year (r = 0.075, p < 0.025). There were no differences in other characteristics including gender, profession, work setting, or serving as main caregiver for a family member and the magnitude of ageism. The phenomenon of ageism exists among physicians and nurses in Russia. Older participants with greater professional seniority and a larger number of older patients had stronger ageism attitudes.

The Association Between Comorbidity, Frailty, and Outdoor Mobility Loss Among Community-Dwelling Individuals 60 Years of Age and Above in Moscow.

To determine the prognostic value of frailty and comorbidity for outdoor mobility loss and mortality in the elderly. The retrospective study was conducted among outpatients aged ≥60 years. Patients with ≥3 chronic illnesses were treated by doctors who had undergone a 72-hour geriatric training. The outdoor low-mobility group comprised patients who failed to visit a doctor because of decreased outdoor mobility during the 3-year follow-up period. The outdoor high-mobility group comprised participants with no outdoor mobility loss. 5678 patients with a mean age of 71.0 ± 0.1 years were included in the study. The risk of outdoor mobility loss rose by 4% per year with men developing it 30% more than women. The effect of frailty was of particular importance because it increased the risk of developing outdoor mobility loss by 70%. Comorbidity was not associated with a higher risk of outdoor mobility loss, but the investigators did not take into account all possible illnesses, or the severity of disease. The loss of outdoor mobility was associated with increase in mortality. Early detection of frailty can help predict outdoor mobility loss and could reduce mortality among older people.

Prevalence of geriatric syndromes among people aged 65 years and older at four community clinics in Moscow.

BACKGROUND: Geriatric syndromes (GSs) are common in older adults and have a significant effect on their quality of life, disability, and use of health care resources. Few studies have assessed the prevalence of GSs in Russia. The aim of this study is to assess the prevalence of GSs among older adults living in the community in Moscow. METHODS: A cross-sectional study was conducted in four community clinics in Moscow. A total of 1,220 patients completed a screening questionnaire, and 356 of them also underwent a comprehensive geriatric assessment (CGA). RESULTS: The mean age of the 1,220 participants was 74.9±6.1 years; 75.5% were women. Based on the questionnaire, 58.3% reported visual or hearing impairment, 58.2% cognitive impairment, 46% mood disorder, 42% difficulty walking, 28.3% urinary incontinence, 21.3% traumatic falls (over the previous year), and 12.2% weight loss. The mean number of GSs per patient was 2.9±1.5. Based on CGA, a decline in Instrumental Activity of Daily Living score was identified in 34.8% of the patients, a risk of malnutrition (Mini-Nutritional Assessment score, 17-23.5) in 25.8%, probable cognitive impairment (Mini-Mental State Examination score <25) in 8.6%, and symptoms of depression (15-item Geriatric Depression Scale score >5) in 36.2%. On the whole, patients demonstrated good mobility (average walking speed, 1±0.2 m/s) and hand grip strength (23.9±6.4 kg in women and 39.1±8.3 kg in men), but poor balance (only 39.4% were able to maintain their balance on one leg for 10 s or more). CONCLUSION: The results of this study demonstrate a high prevalence of GSs among community-dwelling people aged 65 years and older in Moscow. The results provide a better understanding of the needs of older adults in Russia and can facilitate planning for medical and social assistance for this population.

The diagnosis of delirium in an acute-care hospital in Moscow: what does the Pandora's box contain?

BACKGROUND: Delirium, a common problem among hospitalized elderly patients, is not usually diagnosed by doctors for various reasons. The primary aim of this study was to evaluate the effect of a short training course on the identification of delirium and the diagnostic rate of delirium among hospitalized patients aged ≥65 years. The secondary aim was to identify the risk factors for delirium. METHODS: A prospective study was conducted in an acute-care hospital in Moscow, Russia. Six doctors underwent a short training course on delirium. Data collected included assessment by the confusion assessment method for the intensive care units, sociodemographic data, functional state before hospitalization, comorbidity, and hospitalization indices (indication for hospitalization, stay in intensive care unit, results of laboratory tests, length of hospitalization, and in-hospital mortality). RESULTS: Delirium was diagnosed in 13 of 181 patients (7.2%) who underwent assessment. Cognitive impairment was diagnosed more among patients with delirium (30.0% vs 6.1%, P=0.029); Charlson comorbidity index was higher (3.6±2.4 vs 2.3±1.8, P=0.013); and Barthel index was lower (43.5±34.5 vs 94.1±17.0, P=0.000). The length of hospitalization was longer for patients with delirium at 13.9±7.3 vs 8.8±4.6 days (P=0.0001), and two of the 13 patients with delirium died during hospitalization compared with none of the 168 patients without delirium (P=0.0001). CONCLUSION: Although the rate of delirium was relatively low compared with studies from the West, this study proves that an educational intervention among doctors can bring about a significant change in the diagnosis of the condition.

Fever-range whole-body heat treatment stimulates antigen-specific T-cell responses in humans.

Increase in body temperature has been thought to play an important role in the regulation of immune responses, although its precise mechanisms are still under investigation. Here, we examined the effects of physiologically relevant thermal stress on the cytokine production from human peripheral T cells. Volunteers were heated using a whole-body hyperthermia device, the rectal temperature was maintained above 38.5 °C for more than 60 min, and peripheral blood mononuclear cells (PBMCs) were obtained before and after the treatment. When T cells were stimulated with anti-CD3/CD28 antibodies, marked increases in the production of interferon-γ (IFN-γ) and interleukin-2 were observed in PBMCs prepared immediately after and 24h after the treatment. Similarly, enhanced production of IFN-γ in response to the tuberculin purified protein derivative or antigenic viral peptides was also observed immediately after and 24h after the treatment. Fluorescence photo-bleaching analyses showed heat-induced increase of membrane fluidity in T cells, which probably enables them to induce rapid and efficient cluster formation of molecules involved in antigen recognition and signal transduction for T-cell stimulation. We concluded that physiologically relevant thermal stress could efficiently modify T-cell responsiveness to various stimuli, including enhanced responses to specific antigens.

Changes in plasma alpha and gamma tocopherol levels before and after long-term local hyperthermia in cancer patients.

Local hyperthermia is one of the heat therapies for cancer patients. The effect of this therapy is recognized to affect the immune function. On the other hand, researchers have recently suggested that vitamin E has not only antioxidant but also other functions including the immune function. However, the association between local hyperthermia therapy and vitamin E level is not yet well understood. Comparing plasma alpha and gamma tocopherol levels before and after the therapy, the basal levels of both tocopherols in the cancer patients did not significantly differ from those in healthy subjects. However, the interindividual difference in the basal levels was very wide in the cancer patients. After long-term local hyperthermia (more than 70 days), the levels of both tocopherols were significantly higher than the basal levels. This result suggests that long-term local hyperthermia therapy influences plasma tocopherol level in cancer patients; thus, an increase in vitamin E level may play an important role in the therapy of cancer patients.

Increased liver temperature efficiently augments human cellular immune response: T-cell activation and possible monocyte translocation.

Hyperthermia (HT), in combination with other conventional therapeutic modalities, has become a promising approach in cancer therapy. In addition to heat-induced apoptosis, an augmented immunological effect is considered to be a benefit of hyperthermic treatment over chemo- or radiotherapy. Here, we investigated the effect of regional HT targeting the liver on immune cells, especially T cells and antigen-presenting cells, which are important in recognizing and eliminating tumor cells and pathogens such as viruses. In healthy volunteers exposed to such regional HT, both CD4(+) and CD8(+) T cells that express an activation marker CD69 increased transiently at 1 h post-treatment, with a subsequent decrease to base levels at 6 h after the treatment. At 24 h post-treatment, the percentage of CD69-positive cells significantly increased again but only among CD8(+) T cells. IFN-gamma production from PHA-stimulated peripheral blood mononuclear cells was gradually and significantly increased in the 2 days following the heating procedure, peaking at 36 h post-treatment. Furthermore, we found marked increases in plasma levels of IL-1beta and IL-6 starting at 24 h post-treatment. With regard to the number of each leukocyte subpopulation, a transient and dramatic decrease in the number of a subset of monocytes, CD14(+) CD16(-) cells, was observed at 1 h after the hyperthermic treatment, suggesting that the regional HT aimed at the liver may have influenced the extravasation of blood monocytes. No significant changes in T-cell activities or monocyte counts were observed in the volunteers exposed to heating of the lungs or the legs. These results suggest that heating of the liver may efficiently induce cellular immune responses to liver cancers.

Immune-related effects of local hyperthermia in patients with primary liver cancer.

BACKGROUND/AIMS: To investigate immune-related effects of local hyperthermia (HT) with hepatocellular carcinoma (HCC). METHODOLOGY: Immune status after 7 HT was studied in 11 patients (M/F - 9/2; 1st group). The effects were also evaluated during one HT session in 4 of those pts (M/F - 4/0; 2nd group). The HT treatment was performed by means of an 8-MHz capacitive heating device, Thermotron RF8 (Japan). The mean time of one HT session was 60 min, HT was performed 1-2 times a week. In both groups the percentage of T and B cells, CD4+, CD8+ subsets of T cells, the CD4/CD8 ratio and activation of NK cells were evaluated. RESULTS: In the 1st group, CD4/CD8 ratio was decreased significantly (p < 0.05), whereas the relative amount of CD4+ T cells showed a tendency to decrease (p=0.063), and CD8--to increase (p=0.088). An activation of NK cells was observed in patients who had a low or normal pretreatment level of activation. In the 2nd group, there was a significant decrease in the CD4/CD8 ratio by the end of the treatment (p < 0.05) and increased activity of NK cells as early as 20 min after the onset of HT (p < 0.05). CONCLUSIONS: Our results suggest that HT stimulates the immunity of cancer patients by several means and therefore may exhibit indirect anticancer effect. In addition, activation of NK cells by HT may be associated with improved quality of life.

Successful treatment of hepatocellular carcinoma with percutaneous ethanol injection therapy and local hyperthermia.

The patient K.I., a 72-year-old male, was admitted to Nishide Hospital in July 1999 for hemodialysis treatment of end-stage chronic renal failure. At the time of his admission, an ultrasound examination of the patient's liver revealed a large mass in the S5-S8 segment. A hepatocellular carcinoma was suspected from the characteristic mosaic pattern seen with ultrasound and the elevation of alpha-fetoprotein in the serum. The patient's condition was considered to be medically inoperable, due to the patient's adaptation to hemodialysis. Furthermore, transcatheter arterial embolization was not indicated due to the patient's history of hypersensitivity to roentgen-contrast materials. An attempt to palliate the malignancy was made with a combination of local hyperthermia and percutaneous ethanol injection therapy. Magnetic resonance imaging revealed that the tumor structure had changed after 10 days of percutaneous ethanol injection therapy and that 2 months later the tumor size had decreased by about 50%. Moreover, the alpha-fetoprotein level had returned to normal by that time. In addition, this treatment did not cause any disturbance in the liver function. The patient tolerated treatment well. A combined treatment of local hyperthermia with percutaneous ethanol injection therapy appears to be useful in the management of hepatocellular carcinomas, especially in cases in which more aggressive treatment is not acceptable.