Value of exercise capacity and physical activity in the prevention of cardiovascular diseases—brief review of the current literature

A low level of physical activity and decreased exercise capacity are independent risk factors for cardiovascular and all-cause mortality. The assessment of the level of physical activity and its improvement following preventive procedures is methodologically difficult. In population studies, subjective methods, such as questionnaires, activity records and other somewhat imperfect measures (accelerometers, pedometers, and pulse monitors), are used. Direct and especially indirect assessment of physical capacity with exercise tests has become increasingly more accessible and cheap. Both methods have been proved to have high prognostic value. Assessment of physical capacity enables objectification of information on the level and effects of a subjects physical activity acquired via a questionnaire. Taking into account the above-mentioned issues, the role of the assessment of exercise capacity and its improvement is not adequately appreciated. Routine evaluation of exercise capacity has not been included in the current statements on epidemiology and prevention, even in those with an increased Framingham or SCORE risk index in whom low exercise tolerance has been proved to have an unfavorable influence on prognosis. The importance of an increase in the level of physical activity resulting in an improvement in exercise capacity in different population groups should be verified in the near future, but in our opinion there is indirect but strong evidence that actions to improve exercise capacity should become the main goals in the prevention of cardiovascular and all-cause mortality, such as cessation of cigarette smoking, body weight reduction, correction of lipid and carbohydrate metabolism disturbances, and a decrease in blood pressure.     

Context conditioning and extinction in humans: differential contribution of the hippocampus, amygdala and prefrontal cortex

Functional magnetic resonance imaging was used to investigate the role of the hippocampus, amygdala and medial prefrontal cortex (mPFC) in a contextual conditioning and extinction paradigm provoking anxiety. Twenty-one healthy persons participated in a differential context conditioning procedure with two different background colours as contexts. During acquisition increased activity to the conditioned stimulus (CS+) relative to the CS− was found in the left hippocampus and anterior cingulate cortex (ACC). The amygdala, insula and inferior frontal cortex were differentially active during late acquisition. Extinction was accompanied by enhanced activation to CS+ vs. CS− in the dorsal anterior cingulate cortex (dACC). The results are in accordance with animal studies and provide evidence for the important role of the hippocampus in contextual learning in humans. Connectivity analyses revealed correlated activity between the left posterior hippocampus and dACC (BA32) during early acquisition and the dACC, left posterior hippocampus and right amygdala during extinction. These data are consistent with theoretical models that propose an inhibitory effect of the mPFC on the amygdala. The interaction of the mPFC with the hippocampus may reflect the context-specificity of extinction learning.     

Irreversible marrow aplasia after single course of 2-chlorodeoxyadenosine for hairy cell leukaemia preceding by A pandemic 2009-H1N1-associated pneumonia

Hairy cell leukaemia (HCL) is a rare, indolent lymphoproliferative disorder characterized by varying degrees of cytopenias and the presence of malignant B cells with cytoplasmic projections. Cladribine (2-chlorodeoxyadenosine, 2-CdA) is an adenosine deaminase-resistant purine analogue and has been shown to be very effective as a first-line therapeutic option for HCL. The therapy with 2-CdA is found to be well tolerated with a paucity of toxicity. The common side effects include immunosuppression and reversible myelosuppression. We report a HCL patient with A pandemic 2009-H1N1-associated pneumonia who fully recovered after oseltamivir and antibiotics. The subsequent treatment with single 5-day course of 2-CdA resulted in persistent marrow aplasia with fatal systemic aspergillosis.     

Assessing the efficacy of allogeneic hematopoietic stem cells transplantation (allo‐HSCT) by analyzing survival end points in defined groups of acute myeloid leukemia patients: A retrospective,multicenter Polish Adult Leukemia Group study

The importance of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) for survival outcomes in patients with acute myeloid leukemia (AML) currently remains unclear. The study aimed to compare measures of clinical treatment for patients with AML in CR1 (the first complete remission) with or without being subjected to allo‐HSCT. These consisted of leukemia‐free survival (LFS), overall survival (OS), cumulative incidence of relapse (CIR), and non‐relapse mortality disease (NRM). Subjects were 622 patients, median age of 44, forming part of the prospective, randomized, and multicenter clinical Polish Adult Leukemia Group trials during 1999–2008. The Mantel–Byar approach was used to assess allo‐HSCT on survival endpoints, accounting for a changing transplant status. Undergoing allo‐HSCT significantly improved the LFS and OS for the entire group of patients with AML in CR1, along with the DAC induction subgroup and for the group with unfavorable cytogenetics aged 41–60. The CIR demonstrated that allo‐HSCT reduced the risk of relapse for patients with AML in CR1 and those with an unfavorable cytogenetic risk. In addition, the NRM analysis showed that allo‐HSCT significantly reduced the risk of death unrelated to relapse for the entire group of AML patients in CR1 and aged 41–60. The allo‐HSCT treatment particularly benefitted survival for the AML in CR1 group having an unfavorable cytogenetic prognosis. Am. J. Hematol. 90:904–909, 2015. © 2015 Wiley Periodicals, Inc.     

A phase III randomized,multicentre, double blind,active controlled trial to compare the efficacy and safety of two different anagrelide formulations in patients with essential thrombocythaemia – the TEAM-ET 2·0 trial

Anagrelide is an established treatment option for essential thrombocythaemia (ET). A prolonged release formulation was developed with the aim of reducing dosing frequency and improving tolerability, without diminishing efficacy. This multicentre, randomized, double blind, active-controlled, non-inferiority trial investigated the efficacy, safety and tolerability of anagrelide prolonged release (A-PR) over a reference product in high-risk ET patients, either anagrelide-naïve or -experienced. In a 6 to 12-week titration period the individual dose for the consecutive 4-week maintenance period was identified. The primary endpoint was the mean platelet count during the maintenance period (3 consecutive measurements, day 0, 14, 28). Of 112 included patients 106 were randomized. The mean screening platelet counts were 822 × 10⁹/l (95% confidence interval (CI) 707–936 × 10⁹/l) and 797 × 10⁹/l (95% CI 708–883 × 10⁹/l) for A-PR and the reference product, respectively. Both treatments effectively reduced platelet counts, to mean 281 × 10⁹/l for A-PR (95% CI 254–311) and 305 × 10⁹/l (95% CI 276–337) for the reference product (P < 0·0001, for non-inferiority). Safety and tolerability were comparable between both drugs. The novel prolonged-release formulation was equally effective and well tolerated compared to the reference product. A-PR provides a more convenient dosing schedule and will offer an alternative to licensed immediate-release anagrelide formulations.     

AIDE–Acute Illness and Depression in Elderly Patients. Cognitive Behavioral Group Psychotherapy in Geriatric Patients With Comorbid Depression: A Randomized,Controlled Trial

Background

Comorbid depression is highly prevalent in geriatric patients and associated with functional loss, frequent hospital re-admissions, and a higher mortality rate. Cognitive behavioral psychotherapy (CBT) has shown to be effective in older depressive patients living in the community. To date, CBT has not been applied to older patients with acute physical illness and comorbid depression.

Brain correlates of stress-induced analgesia

Stress-induced analgesia (SIA) refers to a reduced pain response after stress exposure, which is mediated by descending pain-inhibitory circuits and may be an indicator of adequate centrally mediated pain control. We used functional magnetic resonance imaging to assess brain mechanisms of SIA in 21 healthy participants. Using a block design series of mildly painful pressure stimuli were applied to the left medial phalanx of the second digit during functional magnetic resonance imaging. Mental arithmetic combined with increasing levels of noise was used as a stressor. Verbal ratings, changes in blood pressure and heart rate confirmed the validity of the stress induction. Post-stress pain thresholds and pain tolerance were significantly higher and post-stress pain and unpleasantness ratings were significantly lower compared to pre-stress levels. SIA led to an increase of the blood-level-dependent oxygenation response in the primary somatosensory cortex, bilaterally in the anterior insula, and secondary somatosensory cortex. The increase in pain tolerance correlated significantly with activation in the rostral anterior cingulate cortex and pain unpleasantness with activation in the dorsal anterior cingulate cortex. SIA seems to activate similar brain networks as placebo analgesia or analgesia mediated by diffuse noxious inhibitory controls and involved sensory, affective and cognitive modulatory circuits.     

Daunorubicin,cytarabine and fludarabine (DAF) for remission induction in relapsed or refractory acute myeloid leukemia. Evaluation of safety,tolerance and early outcome—Polish Adult Leukemia Group (PALG) pilot study

In 1992–1993, synergistic interaction of ribonucleotide reductase inhibitors (fludarabine, cladribine) and cytarabine (Ara-C) increasing Ara-CTP concentration in myeloblasts was proved. Based on these findings and encouraging results of the addition of cladribine to standard daunorubicin+Ara-C induction regimen (DAC) in acute myeloid leukemia (AML), the Polish Adult Leukemia Group (PALG) conducted a pilot study on the administration of cytarabine, daunorubicin, and fludarabine (DAF) as a reinduction treatment of AML to assess tolerance, toxicity, and early outcome. The DAF regimen consisted of daunorubicine 60 mg m⁻² day⁻¹ iv on days 1–3 and fludarabine 25 mg m⁻² day⁻¹ iv on days 1–5 given before cytarabine 200 mg m⁻² day⁻¹ in ci on days 1–7. Thirty-four AML patients with median age 39, 24% relapsed and 76% refractory, were included into the study between September 2003 and August 2004. Achieved response rate in the whole study population was 56%; n = 16 patients with complete remission (CR), and n = 3 patients with partial remission (PR). Fifteen of 16 patients achieved CR after the first course of therapy. Only 9% of total population died before the assessment of remission. All patients developed severe neutropenia. Serious infections were observed in 47% of the cases. Severe thrombocytopenia was observed in 72% of the patients. All patients required substitution of platelet concentrates (median 4), and PRBC (median 5). Severe alopecia, mucositis, vomiting were of low frequency. Liver, kidney, or circulatory failure, diarrhea, or polyneuropathy were not observed. The probability of overall survival (OS) for 1 year for the whole study population (34 patients) and the group of 16 patients in CR was: 44% (95% confidence interval [CI] 36–52%) and 69% (95% CI 55–83%), respectively. The probability of leukemia-free survival (LFS) for 1 year was 38% (95% CI 22–54%). Summarizing, DAF regimen used as the induction therapy in relapsed/refractory AML was well tolerated with acceptable toxicity and early efficacy.     

Autologous stem cell transplantation as consolidation therapy for patients with peripheral T cell lymphoma in first remission: long-term outcome and risk factors analysis

This report is a retrospective analysis of 65 patients with peripheral T cell lymphoma (PTCL), who underwent high-dose therapy and autologous hematopoietic stem cell transplantation (autoHCT) as a consolidation of first response achieved with either induction or salvage chemotherapy. We intended to determine the prognostic factors that influenced outcome after autoHCT and to define the predictive value of the scoring systems most often applied for transplant outcomes. Nineteen patients in either complete or partial remission underwent autoHCT after induction chemotherapy. Forty-six patients received second-line chemotherapy as a consolidation of partial response after induction chemotherapy (n?=?34) or as a salvage therapy after primary induction failure (n?=?12), and thereafter proceeded to autoHCT. Finally, the 36 patients were in complete remission, and 29 in partial remission at autoHCT. The median follow-up of survivors was 53 months (range 7–157 months). The 5-year overall survival and progression-free survival for all patients were 61.5 % (95 % CI 47.0–74.2 %) and 59.4 % (95 % CI 46.1–71.5 %), respectively. In multivariate analysis, bone marrow involvement at diagnosis and less than partial remission after induction chemotherapy were factors independently predictive for overall survival and progression-free survival. The prognostic index for PTCL could reliably stratify the prognosis of PTCL in this analysis.