Effects of exercise mode and intensity on patient-reported outcomes in cancer survivors: a four-arm intervention trial.

PURPOSE: The aim of this study was to compare the effects of different exercise modes (aerobic, resistance) and intensity prescriptions (standard, polarized, undulating) on patient-reported outcomes (PROs) in cancer survivors. METHODS: 107 breast or prostate cancer survivors (52% females, age 58 ± 10 years, 6-52 weeks after primary therapy) performed one out of four training programs, two sessions/week, over 12 weeks: work rate-matched vigorous intensity aerobic training (ATStandard, n = 28) and polarized intensity aerobic training (ATPolarized, n = 26) as well as volume-matched moderate intensity resistance training (RTStandard, n = 26) and daily undulating intensity resistance training (RTUndulating, n = 27). Health-related quality of life (HRQoL, EORTC-QLQ-C30) and cancer-related fatigue (CRF, MFI-20) were assessed at baseline, at the end of intervention and after a 12-week follow-up without further prescribed exercise. RESULTS: Over the intervention period, HRQoL-function-scales of the EORTC-QLQ-C30 improved over time (p = .007), but no group*time interaction was observed (p = .185). Similarly, CRF values of the MFI-20 improved over time (p = .006), but no group*time interaction was observed (p = .663). When including the follow-up period and pooling the AT and the RT groups, HRQoL-function-scales developed differently between groups (p = .022) with further improvements in RT and a decline in AT. For CRF no significant interaction was found, but univariate analyses showed a non-significant trend of more sustainable effects in RT. CONCLUSIONS: AT and RT with different work rate-/volume-matched intensity prescriptions elicits positive effects on HRQoL and CRF, without one regimen being significantly superior to another over the intervention period. However, RT might result in more sustainable effects compared to AT over a follow-up period without any further exercise prescription. CLINICAL TRIAL REGISTRATION: The study was registered at clinicaltrials.gov (NCT02883699).

Erroneous potassium results: preanalytical causes, detection, and corrective actions.

Potassium is one of the most requested laboratory tests. Its level is carefully monitored and maintained in a narrow physiological range. Even slightly altered potassium values may severely impact the patient's health, which is why an accurate and reliable result is of such importance. Even if high-quality analytics are available, there are still numerous ways in which potassium measurements may be biased, all of which occur in the preanalytical phase of the total laboratory testing process. As these results do not reflect the patient's in-vivo status, such results are referred to as pseudo-hyper/hypokalemia or indeed pseudo-normokalemia, depending on the true potassium result. Our goal in this review is to present an in-depth analysis of preanalytical errors that may result in inaccurate potassium results. After reviewing existing evidence on this topic, we classified preanalytical errors impacting potassium results into 4 categories: 1) patient factors like high platelet, leukocytes, or erythrocyte counts; 2) the sample type 3) the blood collection procedure, including inappropriate equipment, patient preparation, sample contamination and others and 4) the tube processing. The latter two include sample transport and storage conditions of whole blood, plasma, or serum as well as sample separation and subsequent preanalytical processes. In particular, we discuss the contribution of hemolysis, as one of the most frequent preanalytical errors, to pseudo-hyperkalemia. We provide a practical flow chart and a tabular overview of all the discussed preanalytical errors including possible underlying mechanisms, indicators for detection, suggestions for corrective actions, and references to the according evidence. We thereby hope that this manuscript will serve as a resource in the prevention and investigation of potentially biased potassium results.

Feasibility of High-Intensity Resistance Training Sessions in Cancer Survivors.

ABSTRACT: Schlüter, K, Schneider, J, Rosenberger, F, and Wiskemann, J. Feasibility of high-intensity resistance training sessions in cancer survivors. J Strength Cond Res 36(9): 2643-2652, 2022-Moderate-intensity resistance training (MIRT) is regarded as safe in cancer survivors (CS), but for high-intensity resistance training (HIRT), evidence is lacking. Hence, in the current exploratory analyses, single sessions of HIRT are compared with MIRT regarding safety and feasibility. Twenty-three of 24 included CS (14 breast and 10 prostate CS, 61.6 ± 9.5 years, body mass index 27.0 ± 4.3 kg·m -2 , 6-52 weeks after end of primary therapy) started a 12-week resistance training (RT) with a daily undulating periodization model including HIRT (90% of 1 repetition maximum [1RM]) and MIRT (67% 1RM) sessions. Parameters of safety (adverse events [AEs] and training-related pain), feasibility (physical and mental exhaustion, sensation of effort, enjoyment, and dropout rate), and adherence were assessed. An alpha level of 0.05 was applied for analyses. Nineteen of 23 training starters (83%) completed all sessions. Fourteen minor AEs occurred. A significantly higher increase for physical exhaustion appeared in HIRT ( p < 0.001). For 18% (HIRT) and 19% (MIRT) of the sessions, training-related pain was reported with no significant difference between intensities. In total, 34% of HIRT and 35% of MIRT sessions were perceived as overstraining or partly overstraining with no significant difference between intensities, but enjoyment (median and quartiles on a 1-7 scale) was high for both (HIRT = 5 [5;6] and MIRT = 5 [4,6]). Our analysis indicates that HIRT sessions do not differ from MIRT sessions concerning safety or feasibility, but training-related pain should be monitored. RT protocols incorporating high-intensity training loads can be applied safely in breast and prostate CS.

Exercise intensity prescription in cancer survivors: ventilatory and lactate thresholds are useful submaximal alternatives to VO2peak.

PURPOSE: Most studies with cancer survivors use percentages of peak oxygen uptake (VO2peak) for intensity prescription. Lactate or ventilatory thresholds might be useful submaximal alternatives, but this has never been investigated. Therefore, we aimed at comparing three training sessions prescribed using %VO2peak (reference), lactate thresholds, and ventilatory thresholds in terms of meeting the vigorous-intensity zone, physiological, and psychological responses. METHODS: Twenty breast (58 ± 10 years) and 20 prostate cancer survivors (68 ± 6 years), 3.6 ± 2.4 months after primary therapy, completed a maximal cardiopulmonary exercise test and three vigorous training sessions in randomized order: 38 min of cycling at 70% VO2peak (M-VO2peak), 97% of individual anaerobic lactate threshold (M-IAT), and 67% between ventilatory thresholds 1 and 2 (M-VT). Heart rate (HR), blood lactate concentration (bLa), perceived exertion, and enjoyment were assessed. RESULTS: Cancer survivors exercised at 75 ± 23, 85 ± 18, and 79 ± 19 W during M-VO2peak, M-IAT, and M-VT (p > .05). Sessions could not be completed in 3, 8, and 6 cases. Session completers showed HR of 82 ± 7, 83 ± 9, and 84 ± 8 %HRpeak and bLa of 3.7 ± 1.9, 3.9 ± 0.9, and 3.9 ± 1.5 mmol·l-1, which was not different between sessions (p > .05). However, variance in bLa was lower in M-IAT compared to M-VO2peak (p = .001) and to M-VT (p = .022). CONCLUSION: All intensity prescription methods on average met the targeted intensity zone. Metabolic response was most homogeneous when using lactate thresholds. IMPLICATIONS FOR CANCER SURVIVORS: Submaximal thresholds are at least as useful as VO2peak for intensity prescription in cancer survivors. Overall, slightly lower percentages should be chosen to improve durability of the training sessions.

Do we underestimate maximal oxygen uptake in cancer survivors? Findings from a supramaximal verification test.

Cancer survivors demonstrate a reduced maximal oxygen uptake, which is clinically relevant in terms of overall survival. However, it remains uncertain whether they attain their "true maximal oxygen uptake" in a cardiopulmonary exercise test (CPET). In the present study, a supramaximal verification bout (Verif) was applied in cancer survivors to confirm attainment of maximal oxygen uptake. Seventy-five participants (age, 61 ± 12 years; n = 43 females with breast cancer and n = 32 males with prostate cancer, 6-52 weeks after primary therapy) performed a CPET on a cycle ergometer and a Verif at 110% peak power output. As verification criterion, maximal oxygen uptake in Verif should not exceed maximal oxygen uptake in CPET by >3%. On average, maximal oxygen uptake was significantly lower in Verif compared with CPET (1.60 ± 0.38 L·min-1 vs. 1.65 ± 0.36 L·min-1, p = .023). On the individual level, n = 51 (68%) satisfied the verification criterion, whereas n = 24 (32%) demonstrated a higher maximal oxygen uptake in Verif. n = 69 (92%) fulfilled ≥2 secondary criteria for maximal exhaustion in the CPET. While maximal oxygen uptake was not underestimated in the CPET on average, one-third of cancer survivors did not attain their true maximal oxygen uptake. Verif appears feasible and beneficial to confirm true maximal oxygen uptake in this population. Furthermore, it might be more reliable than secondary criteria for maximal exhaustion. Novelty In about one-third of cancer survivors, maximal oxygen uptake is underestimated by a CPET. This underestimation of maximal oxygen uptake is not necessarily indicated by secondary criteria for maximal exhaustion. A supramaximal verification bout appears feasible and helpful for the determination of maximal oxygen uptake in cancer survivors.

Feasibility of Two High-Intensity Interval Training Protocols in Cancer Survivors.

PURPOSE: High-intensity interval training (HIIT) is a time-efficient and promising tool for enhancing physical fitness. However, there is lack of research concerning safety and feasibility of HIIT in cancer survivors. Therefore, two different HIIT protocols were investigated in terms of safety, feasibility, and acute exercise responses. METHODS: Forty cancer survivors (20 breast and 20 prostate cancer survivors, 62.9 ± 9.2 yr, BMI 27.4 ± 3.9 kg·m, 6 to 52 wk after the end of primary therapy) completed a maximal cardiopulmonary exercise test and two HIIT protocols on a cycle ergometer: 10 × 1 min at peak power output (10 × 1) and 4 × 4 min at 85%-95% peak HR (4 × 4). Safety (adverse events), acute physiological responses (HR, blood lactate concentration) and acute psychological responses (RPE, enjoyment) were recorded. RESULTS: No major but three minor adverse events occurred. Ninety-five percent of participants were able to complete each HIIT protocol. Estimated energy expenditure (159 ± 15 vs 223 ± 45 kcal, P < 0.001), HR (128 ± 20 vs 139 ± 18 bpm; P < 0.001), blood lactate concentration (5.4 ± 1.0 vs 5.9 ± 1.9 mmol·L; P = 0.035), and RPE legs/breathing (13.8 ± 2.0/13.1 ± 2.0 vs 14.6 ± 2.1/14.3 ± 2.0; P = 0.038/0.003) were significantly higher in the 4 × 4. Enjoyment did not differ between protocols (P = 0.301). CONCLUSIONS: The two HIIT protocols as single sessions appear safe and in the vast majority of breast and prostate cancer survivors after the end of primary therapy also feasible and enjoyable. The 4 × 4 elicited higher energy expenditure and higher cardio-circulatory and metabolic strain and might therefore be preferred if a high training stimulus is intended.

Wet biowaste digestion: ADM1 model improvement by implementation of known genera and activity of propionate oxidizing bacteria.

Anaerobic digestion of biowaste not only reduces environmental burden but also plays an important role for sustainable energy supply. For process optimization simulation based on the Anaerobic Digestion Model No. 1 (ADM1) is commonly used. The ADM1 was extended to include the known three genera of propionate oxidizing bacteria (POB) and the two routes of propionate degradation (methyl-malonyl CoA and C6-dismutation pathway). Kinetic parameters for anaerobic propionate oxidation by single strains of the three propionate oxidizing genera were determined from defined tri-cultures of the POB with hydrogenotrophic and acetotrophic methanogens and implemented into ADM1. The such improved model ADM1xpro was evaluated with operational data from a full scale wet biowaste digestion plant. Predicted amounts of biogas and composition with ADM1xpro (2201 m³ d-1, 68.1 % CH4 and 31.9 % CO2) correlated well with full-scale process data (2171 m³ d-1, 67.5 % CH4 and 31.9 % CO2).

Aberrant peak lactate response in MS.

BACKGROUND: The peak blood lactate response to an exhaustive exercise test in a number of chronic conditions has been shown to differ from that seen in healthy, untrained individuals. However, this has not been investigated for patients with multiple sclerosis (MS). OBJECTIVE: The main objective was to determine and compare the peak blood lactate response to exercise and the maximal workload between two groups of MS patients with different illness severity. METHODS: Twenty-five patients with a relapsing-remitting disease course (Group RR) and 41 patients with a secondary- or primary chronic progressive disease course (group CP) performed an exhaustive incremental bicycle ergometry. Peak blood lactate, maximal workload, peak oxygen consumption and maximal heart rate were measured. RESULTS: The peak blood lactate levels and maximal workload differed significantly between the groups (group CP < group RR; p < 0.001). Furthermore spiroergometric peak performance markers in both groups were significantly lower than predicted for healthy age and sex matched untrained groups. CONCLUSION: A reduced peak blood lactate response to exercise is a novel finding for MS patients. This calls into doubt if the lactate performance tests and lactate thresholds used for healthy individuals can be transferred to MS patients.

Physical condition, nutritional status, fatigue, and quality of life in oncological out-patients.

OBJECTIVE: Early detection of limited physical activity and nutritional deficiencies in cancer survivors could contribute to early treatment and preservation of quality of life. The aim of this study is to describe the association of physical condition and nutritional status with fatigue and quality of life in oncological out-patients. METHODS: Data in this descriptive study was collected on bioelectrical impedance analysis, postural stability (stability index), body mass index, Karnofsky Index, quality of life (Short-Form 36-Item Health Survey) and fatigue (multidimensional fatigue inventory-20) in a consecutive sample of 203 oncological out-patients. Phase angle was calculated from bioelectrical impedance analysis. Values were intercorrelated and compared to appropriate standard values. RESULTS: Phase angle and stability index outcomes were far below the values of a healthy population of similar age (p < 0.001). Quality of life was significantly lower than in the normal population (p < 0.001), and the level of fatigue was significantly higher (p < 0.001). Phase angle correlated with Karnofsky Index (p = 0.002) and Short-Form 36-Item Health Survey Summary physical function (p < 0.001). Furthermore, multidimensional fatigue inventory-20 scales 'physical fatigue' and 'reduced activity' were significantly associated with phase angle (p = 0.04, p = 0.005). Stability indices correlated with Short-Form 36-Item Health Survey physical function. CONCLUSION: The physical condition and the nutritional status are key components determining the individual quality of life of oncological out-patients. These variables also showed an association with the manifestation of fatigue. Results highlight the need for interdisciplinary cooperation to detect physical, nutritional and psychological deficiencies in oncological out-patients.

Insulin Resistance May Contribute to Upregulation of Adhesion Molecules on Endothelial Cells in Psoriatic Plaques.

Psoriasis primarily affects the skin, but also has a systemic dimension and is associated with severe comorbidities. Since endothelial cells play an important role in psoriasis as well as in the development of cardiovascular comorbidities, we investigated whether a common mechanism, namely cytokine-induced insulin resistance, underlies both pathologies. Activation of the insulin pathway was studied in psoriatic skin and dermal endothelial cells. Expression of adhesion molecules was assessed by flow cytometry, as well as their biological function in flow chamber experiments. The phosphorylation status of Akt, a central kinase in the insulin pathway, suggests that endothelial cells within psoriatic plaques are rendered insulin resistant by pro-inflammatory cytokines. Insulin counteracts the expression of adhesion molecules, but has limited effects on interactions between T cells and endothelial cells. Pro-inflammatory cytokines induce insulin resistance in endothelial cells, which may contribute to the development of the inflammatory infiltrate in psoriasis.

Tumor suppressor activity of profilin requires a functional actin binding site.

Profilin 1 (PFN1) is a regulator of the microfilament system and is involved in various signaling pathways. It interacts with many cytoplasmic and nuclear ligands. The importance of PFN1 for human tissue differentiation has been demonstrated by the findings that human cancer cells, expressing conspicuously low PFN1 levels, adopt a nontumorigenic phenotype upon raising their PFN1 level. In the present study, we characterize the ligand binding site crucial for profilin's tumor suppressor activity. Starting with CAL51, a human breast cancer cell line highly tumorigenic in nude mice, we established stable clones that express PFN1 mutants differentially defective in ligand binding. Clones expressing PFN1 mutants with reduced binding to either poly-proline-stretch ligands or phosphatidyl-inositol-4,5-bisphosphate, but with a functional actin binding site, were normal in growth, adhesion, and anchorage dependence, with only a weak tendency to elicit tumors in nude mice, similar to controls expressing wild-type PFN1. In contrast, clones expressing a mutant with severely reduced capacity to bind actin still behaved like the parental CAL51 and were highly tumorigenic. We conclude that the actin binding site on profilin is instrumental for normal differentiation of human epithelia and the tumor suppressor function of PFN1.

Complex formation between the postsynaptic scaffolding protein gephyrin, profilin, and Mena: a possible link to the microfilament system.

Gephyrin is an essential component of the postsynaptic cortical protein network of inhibitory synapses. Gephyrin-based scaffolds participate in the assembly as well as the dynamics of receptor clusters by connecting the cytoplasmic domains of glycine and GABA(A) receptor polypeptides to two cytoskeletal systems, microtubules and microfilaments. Although there is evidence for a physical linkage between gephyrin and microtubules, the interaction between gephyrin and microfilaments is not well understood so far. Here, we show that neuronal gephyrin interacts directly with key regulators of microfilament dynamics, profilin I and neuronal profilin IIa, and with microfilament adaptors of the mammalian enabled (Mena)/vasodilator stimulated phosphoprotein (VASP) family, including neuronal Mena. Profilin and Mena/VASP coprecipitate with gephyrin from tissue and cells, and complex formation requires the E-domain of gephyrin, not the proline-rich central domain. Consequently, gephyrin is not a ligand for the proline-binding motif of profilins, as suspected previously. Instead, it competes with G-actin and phospholipids for the same binding site on profilin. Gephyrin, profilin, and Mena/VASP colocalize at synapses of rat spinal cord and cultivated neurons and in gephyrin clusters expressed in transfected cells. Thus, Mena/VASP and profilin can contribute to the postulated linkage between receptors, gephyrin scaffolds, and the microfilament system and may regulate the microfilament-dependent receptor packing density and dynamics at inhibitory synapses.