Optimizing Recovery in Elderly Patients: Anabolic Benefits of Glucose Supplementation during the Rehydration Period.

BACKGROUND: Since many acutely admitted older adults display signs of dehydration, treatment using balanced crystalloids is an important part of medical care. Additionally, many of these patients suffer from chronic malnutrition. We speculated that the early addition of glucose might ameliorate the hospital-related drop of caloric intake and modify their catabolic status. METHODS: We included patients 78 years and older, admitted acutely for non-traumatic illnesses. The patients were randomized into either receiving balanced crystalloid (PlasmaLyte; group P) or balanced crystalloid enriched with 100 g of glucose per liter (group G). The information about fluid balance and levels of minerals were collected longitudinally. RESULTS: In the G group, a significantly higher proportion of patients developed signs of refeeding syndrome, i.e., drops in phosphates, potassium and/or magnesium when compared to group P (83.3 vs. 16.7%, p < 0.01). The drop in phosphate levels was the most pronounced. The urinalysis showed no differences in the levels of these minerals in the urine, suggesting their uptake into the cells. There were no differences in the in-hospital mortality or in the 1-year mortality. CONCLUSION: The short-term administration of balanced crystalloids with glucose induced an anabolic shift of electrolytes in acutely admitted older adults.

Proximal femoral fractures in patients with COVID-19 : Pneumonia and admission from a nursing home are the strongest predictors of mortality.

BACKGROUND: Proximal femoral fractures are severe injuries in geriatric patients. Additionally, geriatric patients are at a high risk of death due to coronavirus disease 2019 (COVID-19). OBJECTIVE: To identify predictors of mortality in geriatric patients with COVID-19 and concurrent proximal femoral fractures. MATERIAL AND METHODS: Patients who underwent surgical treatment for proximal femoral fractures and also tested positive for COVID-19 were included. The age, gender, the American Society of Anesthesiology (ASA) score and the admission from a nursing home were considered as variables. The rate of reoperations, the mortality at 3 months and discharge home were evaluated as outcomes. RESULTS: In this study 46 patients with COVID-19 (female/male 31/15, median age 87.0 years with an interquartile range [IQR] of 9.8 years) met the inclusion criteria. Of these, 32 patients (69.6%) had to be cared for in the intensive care unit and 26 patients (56.5%) had a severe course of COVID-19 with pneumonia. The median length of hospital stay for survivors was 19 (IQR 17.5) days and 4 of the patients (8.7%) required surgical revision. The in-hospital and 3­month mortality were 40.0% (n = 17) and 43.5% (n = 20), respectively. The factors which influenced the in-hospital and 3­month mortality rates were admission from a nursing home, the presence of pneumonia (increased the risk of death) and female gender (protective). CONCLUSION: The occurrence of COVID-19 in patients with proximal femoral fractures has a high mortality. Admission from a nursing home and the presence of pneumonia increased the risk of death, whereas women were at lower risk.

Should Carbohydrate Intake Be More Liberal during Oral and Enteral Nutrition in Type 2 Diabetic Patients?

Carbohydrate (CHO) intake in oral and enteral nutrition is regularly reduced in nutritional support of older patients due to the high prevalence of diabetes (usually type 2-T2DM) in this age group. However, CHO shortage can lead to the lack of building blocks necessary for tissue regeneration and other anabolic processes. Moreover, low CHO intake decreases CHO oxidation and can increase insulin resistance. The aim of our current study was to determine the extent to which an increased intake of a rapidly digestible carbohydrate-maltodextrin-affects blood glucose levels monitored continuously for one week in patients with and without T2DM. Twenty-one patients (14 T2DM and seven without diabetes) were studied for two weeks. During the first week, patients with T2DM received standard diabetic nutrition (250 g CHO per day) and patients without diabetes received a standard diet (350 g of CHO per day). During the second week, the daily CHO intake was increased to 400 in T2DM and 500 g in nondiabetic patients by addition of 150 g maltodextrin divided into three equal doses of 50 g and given immediately after the main meal. Plasma glucose level was monitored continually with the help of a subcutaneous sensor during both weeks. The increased CHO intake led to transient postprandial increase of glucose levels in T2DM patients. This rise was more manifest during the first three days of CHO intake, and then the postprandial peak hyperglycemia was blunted. During the night's fasting period, the glucose levels were not influenced by maltodextrin. Supplementation of additional CHO did not influence the percentual range of high glucose level and decreased a risk of hypoglycaemia. No change in T2DM treatment was indicated. The results confirm our assumption that increased CHO intake as an alternative to CHO restriction in type 2 diabetic patients during oral and enteral nutritional support is safe.

The experiences of early career geriatricians throughout Europe during the COVID-19 pandemic.

The COVID-19 pandemic has severely affected older adults and brought about unprecedented challenges to geriatricians. We aimed to evaluate the experiences of early career geriatricians (residents or consultants with up to 10 years of experience) throughout Europe using an online survey. We obtained 721 responses. Most of the respondents were females (77.8%) and residents in geriatric medicine (54.6%). The majority (91.4%) were directly involved in the care of patients with COVID-19. The respondents reported moderate levels of anxiety and feelings of being overloaded with work. The anxiety levels were higher in women than in men. Most of the respondents experienced a feeling of a strong restriction on their private lives and a change in their work routine. The residents also reported a moderate disruption in their training and research activities. In conclusion, early career geriatricians experienced a major impact of COVID-19 on their professional and private lives.

The surgical treatment of renal tumors - a 30-month evaluation of the post operative period at a secondary center. / Tratamiento quirúrgico de tumores renales- evaluación postoperatoria a 30 meses en un centro secundario.

OBJECTIVES: Our aim was to compare nephrectomies with kidney resections in terms of their influence on renal function and blood loss. We compared laparoscopic nephrectomies with open nephrectomies in terms of the length of the procedure and the hospital stay. METHODS: We retrospectively included patients who were operated for renal tumors (n=148) between January 2016 to July 2018 in a single secondary center. We considered the type of operation (nephrectomies versus kidney resections), the approach to the kidney (open or laparoscopic) and compared the following outcomes: the length of the operation, perioperative blood loss, the changes in hemoglobin concentrations, in creatinine levels and in the estimated glomerular filtration rate (eGFR). RESULTS: Kidney resections when compared to nephrectomies resulted in a significantly smaller decline in the estimated glomerular filtration rates (ß=38.78 ml/min;p<0.001). When compared to baseline values, there was a significant drop in the eGFR on both day 1 and 3-6 months after the operation in the nephrectomy group (p<0.001 for both intervals); this drop was not present in the resection group. The decline in hemoglobin levels was bigger in the resection than in the nephrectomy group. However, during a follow up evaluation 3-6 months after the procedures, the values did not differ between the groups. We then compared open nephrectomies with laparoscopic nephrectomies. Laparoscopy involved more time (ß=38.6 minutes; p<0.001), was used for early stage tumors and involved a shorter hospital stay (ß=3 days;p<0.001) in comparison to open surgeries. CONCLUSIONS: Data from our center confirmed the findings from other literature that nephron-sparing surgeries lead to a lower decline in kidney function than with nephrectomies. This benefit for kidney function also remained during the follow-up. When performing a nephrectomy, the laparoscopic approach offers a shorter hospital stay for the patient than with an open surgery.

OBJETIVOS: Nuestro objetivo fue comparar las nefrectomías en términos de resultados de función renal y perdida de sangre. Comparamos las nefrectomías laparoscópicas con las abiertas en términos de duración de la cirugía y estancia hospitalaria. MÉTODOS: Se incluyeron retrospectivamente pacientes que fueron operados por tumores renales (n=148) entre enero 2016 y julio 2018 en un único centro secundario. Consideramos el tipo de cirugía (nefrectomía vs resección renal), la técnica quirúrgica (abierta vs laparoscópica) y comparando sus resultados: tiempo de cirugía, perdida sanguínea, cambios en la concentración hemoglobina, niveles de creatinina y filtrado glomerular estimado. RESULTADOS: Las resecciones renales en comparación con las nefrectomías presentaron una caída estimada de FG menor (ß=38,78 ml/min; p<0,001). Al comparar con los valores basales, se mostro una caída significativa de FG en los días 1 y a los 3-6 meses después de la operación en el grupo nefrectomía (p<0,001 en ambos intervalos); esta caída no estaba presente en el grupo de resección renal. La caída de hemoglobina fue superior en las resecciones renales en comparación con las nefrectomías. Aunque durante el seguimiento de 3 a 6 meses después del procedimiento, el valor no cambio entre grupos. Comparamos también las nefrectomías abiertas con laparoscópicas. Las laparoscópicas implican más tiempo (ß=38,6 minutos; p<0,001), se usaron en estadíos más precoces e implicaron menos estancia hospitalaria en comparación con las abiertas (ß=3 días; p<0,00). CONCLUSIONES: Los datos de nuestro centro confirmanlos hallazgos que la cirugía de resección renal implica menos caída de FG que las nefrectomías. Este beneficio se mantuvo en el seguimiento. Cuando realizamos una nefrectomía, la laparoscopia aporta una menor estancia hospitalaria que la cirugía abierta.

Superoxide produced by mitochondrial site IQ inactivates cardiac succinate dehydrogenase and induces hepatic steatosis in Sod2 knockout mice.

Superoxide produced by mitochondria has been implicated in numerous physiologies and pathologies. Eleven different mitochondrial sites that can produce superoxide and/or hydrogen peroxide (O2.-/H2O2) have been identified in vitro, but little is known about their contributions in vivo. We introduce novel variants of S1QELs and S3QELs (small molecules that suppress O2.-/H2O2 production specifically from mitochondrial sites IQ and IIIQo, respectively, without compromising bioenergetics), that are suitable for use in vivo. When administered by intraperitoneal injection, they achieve total tissue concentrations exceeding those that are effective in vitro. We use them to study the engagement of sites IQ and IIIQo in mice lacking functional manganese-superoxide dismutase (SOD2). Lack of SOD2 is expected to elevate superoxide levels in the mitochondrial matrix, and leads to severe pathologies and death about 8 days after birth. Compared to littermate wild-type mice, 6-day-old Sod2-/- mice had significantly lower body weight, lower heart succinate dehydrogenase activity, and greater hepatic lipid accumulation. These pathologies were ameliorated by treatment with a SOD/catalase mimetic, EUK189, confirming previous observations. A 3-day treatment with S1QEL352 decreased the inactivation of cardiac succinate dehydrogenase and hepatic steatosis in Sod2-/- mice. S1QEL712, which has a distinct chemical structure, also decreased hepatic steatosis, confirming that O2.- derived specifically from mitochondrial site IQ is a significant driver of hepatic steatosis in Sod2-/- mice. These findings also demonstrate the ability of these new S1QELs to suppress O2.- production in the mitochondrial matrix in vivo. In contrast, suppressing site IIIQo using S3QEL941 did not protect, suggesting that site IIIQo does not contribute significantly to mitochondrial O2.- production in the hearts or livers of Sod2-/- mice. We conclude that the novel S1QELs are effective in vivo, and that site IQ runs in vivo and is a significant driver of pathology in Sod2-/- mice.

Antiplatelet therapy in patients with Covid-19: A retrospective observational study.

Introduction: Covid-19 is associated with a high risk of venous thromboembolism. In addition, cases of arterial thromboembolism were also reported. We investigated the effect of antiplatelet therapy on the disease course. Methods: We evaluated a cohort of inpatients with Covid-19 (n â€‹= â€‹152). We recorded the patient's demographic data, their comorbidities, medication use including the use of antiplatelets and anticoagulants, laboratory findings and data about mechanical ventilation. We then separated the patient's outcomes into either being "bad" (dead or referral to higher level of care) or "good" (discharged). Then we evaluated the factors that contributed to the patient needing ventilatory support and to showing typical radiological findings. Results: In our cohort, 21 patients received ventilatory support whereas 131 did not require the use of ventilators. 127 patients had good outcomes and 25 had bad outcomes. By using multivariate analysis, we found that the need for ventilatory support was the strongest predictor of a bad outcome. All patients who were on ventilators displayed typical radiological findings. The factors predicting the need for ventilatory support were LDH and CRP levels, the presence of cardiac conduction abnormalities as well as chronic lung conditions. Cardiac conduction abnormalities, LDH and CRP levels, and the use of antiplatelets, were factors that predicted typical radiological findings. Conclusions: There was a higher incidence of typical radiological findings in patients on antiplatelet medication. However, it did not translate into changes in the ventilation requirement or in the outcome. The need for mechanical ventilation was the strongest predictor of a bad outcome.

Chronic non-healing wounds in geriatrics.

Chronic non-healing wounds represent a frequent comorbidity among geriatric patients. Non-healing wounds increase patients morbidity and mortality and significantly decrease their quality of life. Prognosis of these wounds depends on etiology, overall health condition of the patient and also on the proper treatment. In this review we outline the classification of non-healing wounds and focus in more detail on the most frequent types: venous and arterial leg ulcers, diabetic foot syndrome and pressure ulcers. Key words: diabetic foot ulcers - chronic venous insufficiency - chronic wounds - limb ischemia - non-healing wounds - pressure ulcers.

Production of superoxide and hydrogen peroxide from specific mitochondrial sites under different bioenergetic conditions.

Mitochondrial production of superoxide and hydrogen peroxide is potentially important in cell signaling and disease. Eleven distinct mitochondrial sites that differ markedly in capacity are known to leak electrons to oxygen to produce O2̇̄ and/or H2O2 We discuss their contributions to O2̇̄/H2O2 production under native conditions in mitochondria oxidizing different substrates and in conditions mimicking physical exercise and the changes in their capacities after caloric restriction. We review the use of S1QELs and S3QELs, suppressors of mitochondrial O2̇̄/H2O2 generation that do not inhibit oxidative phosphorylation, as tools to characterize the contributions of specific sites in situ and in vivo.

Effects of Epigallocatechin Gallate on Tert-Butyl Hydroperoxide-Induced Mitochondrial Dysfunction in Rat Liver Mitochondria and Hepatocytes.

Epigallocatechin gallate (EGCG) is a green tea antioxidant with adverse effects on rat liver mitochondria and hepatocytes at high doses. Here, we assessed whether low doses of EGCG would protect these systems from damage induced by tert-butyl hydroperoxide (tBHP). Rat liver mitochondria or permeabilized rat hepatocytes were pretreated with EGCG and then exposed to tBHP. Oxygen consumption, mitochondrial membrane potential (MMP), and mitochondrial retention capacity for calcium were measured. First, 50 µM EGCG or 0.25 mM tBHP alone increased State 4 Complex I-driven respiration, thus demonstrating uncoupling effects; tBHP also inhibited State 3 ADP-stimulated respiration. Then, the coexposure to 0.25 mM tBHP and 50 µM EGCG induced a trend of further decline in the respiratory control ratio beyond that observed upon tBHP exposure alone. EGCG had no effect on MMP and no effect, in concentrations up to 50 µM, on mitochondrial calcium retention capacity. tBHP led to a decline in both MMP and mitochondrial retention capacity for calcium; these effects were not changed by pretreatment with EGCG. In addition, EGCG dose-dependently enhanced hydrogen peroxide formation in a cell- and mitochondria-free medium. Conclusion. Moderate nontoxic doses of EGCG were not able to protect rat liver mitochondria and hepatocytes from tBHP-induced mitochondrial dysfunction.

JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age.

Chronic, low grade, sterile inflammation frequently accompanies aging and age-related diseases. Cellular senescence is associated with the production of proinflammatory chemokines, cytokines, and extracellular matrix (ECM) remodeling proteases, which comprise the senescence-associated secretory phenotype (SASP). We found a higher burden of senescent cells in adipose tissue with aging. Senescent human primary preadipocytes as well as human umbilical vein endothelial cells (HUVECs) developed a SASP that could be suppressed by targeting the JAK pathway using RNAi or JAK inhibitors. Conditioned medium (CM) from senescent human preadipocytes induced macrophage migration in vitro and inflammation in healthy adipose tissue and preadipocytes. When the senescent cells from which CM was derived had been treated with JAK inhibitors, the resulting CM was much less proinflammatory. The administration of JAK inhibitor to aged mice for 10 wk alleviated both adipose tissue and systemic inflammation and enhanced physical function. Our findings are consistent with a possible contribution of senescent cells and the SASP to age-related inflammation and frailty. We speculate that SASP inhibition by JAK inhibitors may contribute to alleviating frailty. Targeting the JAK pathway holds promise for treating age-related dysfunction.

In vitro toxicity of epigallocatechin gallate in rat liver mitochondria and hepatocytes.

Epigallocatechin-3-gallate (EGCG) is the main compound of green tea with well-described antioxidant, anti-inflammatory, and tumor-suppressing properties. However, EGCG at high doses was reported to cause liver injury. In this study, we evaluated the effect of EGCG on primary culture of rat hepatocytes and on rat liver mitochondria in permeabilized hepatocytes. The 24-hour incubation with EGCG in concentrations of 10 µmol/L and higher led to signs of cellular injury and to a decrease in hepatocyte functions. The effect of EGCG on the formation of reactive oxygen species (ROS) was biphasic. While low doses of EGCG decreased ROS production, the highest tested dose induced a significant increase in ROS formation. Furthermore, we observed a decline in mitochondrial membrane potential in cells exposed to EGCG when compared to control cells. In permeabilized hepatocytes, EGCG caused damage of the outer mitochondrial membrane and an uncoupling of oxidative phosphorylation. EGCG in concentrations lower than 10 µmol/L was recognized as safe for hepatocytes in vitro.

Antioxidative effect of epigallocatechin gallate against D-galactosamine-induced injury in primary culture of rat hepatocytes.

Literature data support that green tea and its major component epigallocatechin gallate (EGCG) have powerful antioxidant effects. Contrary, hepatotoxicity can be induced by high-dose EGCG. The timing of exposure to green tea in relation to administration of hepatotoxic agent plays an import role too. The aim of our work was a verification of antioxidative effect of EGCG on D-galactosamine-induced injury in primary culture of rat hepatocytes. Hepatocytes were incubated with EGCG at concentrations of 1.25-10 µM and toxic D-galactosamine (GalN) for 24 hrs. Alternatively, hepatocytes were pretreated with EGCG for 24 hrs, and then incubated with EGCG and GalN for further 24 hrs. Cytotoxicity was analysed by lactate dehydrogenase activity, functional capacity by albumin production. Oxidative stress was evaluated from a production of malondialdehyde and glutathione content in the cells. EGCG protected hepatocytes against GalN-induced cytotoxicity but preventive treatment of intact hepatocytes with EGCG was required to diminish the development of hepatocyte injury. Oxidative stress induced in our study seems to overcome the ability of hepatocytes to improve GSH depletion and albumin production. Prolongation of the pretreatment with EGCG could be a promising strategy leading to amelioration of its hepatoprotective effect.

The effect of epigallocatechin gallate on hepatocytes isolated from normal and partially hepatectomized rats.

Epigallocatechin gallate (EGCG) is an antioxidant found in green tea. In this study, male Wistar rats were subjected either to partial hepatectomy (PHx), or a sham operation (LAP). Twenty-four hours after surgery, hepatocytes were isolated and treated with various concentrations of EGCG for up to 72 h. We then measured markers of cell viability, oxidative stress, DNA synthesis, and caspase activity. Morphological criteria, cell viability tests, and albumin synthesis revealed toxicity starting at 10 µmol/L. DNA synthesis was higher in hepatocytes isolated from rats after PHx and inhibited by EGCG. Furthermore, EGCG increased the activity of caspases 3 and 7, seen more in hepatocytes from PHx rats. In conclusion, EGCG at a concentration of 10 µmol/L was toxic for hepatocytes isolated from both PHx and LAP rats.

Epigallocatechin gallate does not accelerate the early phase of liver regeneration after partial hepatectomy in rats.

BACKGROUND: Two-thirds partial hepatectomy (PHx) is an established model for the study of liver regeneration after resection. This process is accompanied by oxidative stress. AIMS: In our study, we tested the effect of epigallocatechin gallate (EGCG), a green tea antioxidant, on the early phase of liver regeneration after PHx. METHODS: Male Wistar rats were divided into five groups: (I) laparotomy + water for intraperitoneal injections, (II) laparotomy + EGCG 50 mg/kg body weight, (III) PHx + water for injections, (IV) PHx + EGCG 20 mg/kg and (V) PHx + EGCG 50 mg/kg, for 3 consecutive days. The rats were killed 24 h after surgery. Biochemical analysis of rat sera was performed. Histological samples were stained with hematoxylin & eosin and bromodeoxyuridine (BrdU). In hepatectomized rats, we also measured plasma malondialdehyde, tissue malondialdehyde, glutathione and cytokines levels, the activity of caspases 3/7, expression of Nqo-1 and HO-1 genes at the mRNA level, and expression of p21, p-p27 and p-p53 genes at the protein level. RESULTS: We observed lower accumulation of BrdU in group V when compared to groups III and IV. The activity of caspases 3/7 and expression of p-p53 were lower in group V than in groups III and IV. Tissue levels of IL-6 were lower in group V when compared to group III. Significant differences were not noted in other parameters. CONCLUSIONS: Administration of EGCG did not stimulate early phase liver regeneration in rats after PHx. There was even lower DNA synthesis in the group treated with a high dose of EGCG.

Is rat liver affected by non-alcoholic steatosis more susceptible to the acute toxic effect of thioacetamide?

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic condition of the liver in the western world. There is only little evidence about altered sensitivity of steatotic liver to acute toxic injury. The aim of this project was to test whether hepatic steatosis sensitizes rat liver to acute toxic injury induced by thioacetamide (TAA). Male Sprague-Dawley rats were fed ad libitum a standard pelleted diet (ST-1, 10% energy fat) and high-fat gelled diet (HFGD, 71% energy fat) for 6 weeks and then TAA was applied intraperitoneally in one dose of 100 mg/kg. Animals were sacrificed in 24-, 48- and 72-h interval after TAA administration. We assessed the serum biochemistry, the hepatic reduced glutathione, thiobarbituric acid reactive substances, cytokine concentration, the respiration of isolated liver mitochondria and histopathological samples (H+E, Sudan III, bromodeoxyuridine [BrdU] incorporation). Activities of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase and concentration of serum bilirubin were significantly higher in HFGD groups after application of TAA, compared to ST-1. There were no differences in activities of respiratory complexes I and II. Serum tumour necrosis factor alpha at 24 and 48 h, liver tissue interleukin-6 at 72 h and transforming growth factor ß1 at 24 and 48 h were elevated in TAA-administrated rats fed with HFGD, but not ST-1. TAA-induced centrilobular necrosis and subsequent regenerative response of the liver were higher in HFGD-fed rats in comparison with ST-1. Liver affected by NAFLD, compared to non-steatotic liver, is more sensitive to toxic effect of TAA.