Abstract
Background
Clarithromycin may act as immune-regulating treatment in sepsis and acute respiratory dysfunction syndrome. However, clinical evidence remains inconclusive. We aimed to evaluate ...whether clarithromycin improves 28-day mortality among patients with sepsis, respiratory and multiple organ dysfunction syndrome.
Methods
We conducted a multicenter, randomized, clinical trial in patients with sepsis. Participants with ratio of partial oxygen pressure to fraction of inspired oxygen less than 200 and more than 3 SOFA points from systems other than the respiratory function were enrolled between December 2017 and September 2019. Patients were randomized to receive 1 gr of clarithromycin or placebo intravenously once daily for 4 consecutive days. The primary endpoint was 28-day all-cause mortality. Secondary outcomes were 90-day mortality; sepsis response (defined as at least 25% decrease in SOFA score by day 7); sepsis recurrence; and differences in peripheral blood cell populations and leukocyte transcriptomics.
Results
Fifty-five patients were allocated to each arm. By day 28, 27 (49.1%) patients in the clarithromycin and 25 (45.5%) in the placebo group died (risk difference 3.6% 95% confidence interval (CI) − 15.7 to 22.7;
P
= 0.703, adjusted OR 1.03 95%CI 0.35–3.06;
P
= 0.959). There were no statistical differences in 90-day mortality and sepsis response. Clarithromycin was associated with lower incidence of sepsis recurrence (OR 0.21 95%CI 0.06–0.68;
P
= 0.012); significant increase in monocyte HLA-DR expression; expansion of non-classical monocytes; and upregulation of genes involved in cholesterol homeostasis. Serious and non-serious adverse events were equally distributed.
Conclusions
Clarithromycin did not reduce mortality among patients with sepsis with respiratory and multiple organ dysfunction. Clarithromycin was associated with lower sepsis recurrence, possibly through a mechanism of immune restoration.
Clinical trial registration
clinicaltrials.gov identifier
NCT03345992
registered 17 November 2017; EudraCT 2017-001056-55.
Patients with chronic kidney disease (CKD) experience imbalance between oxygen reactive species (ROS) production and antioxidant defenses leading to cell and tissue damage. However, it remains ...unclear at which stage of renal insufficiency the redox imbalance becomes more profound. The aim of this systematic review was to provide an update on recent advances in our understanding of how the redox status changes in the progression of renal disease from predialysis stages 1 to 4 to end stage 5 and whether the various treatments and dialysis modalities influence the redox balance. A systematic review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA guidelines. In total, thirty-nine studies met the inclusion criteria and were reviewed. Even from an early stage, imbalance in redox status is evident and as the kidney function worsens it becomes more profound. Hemodialysis therapy per se seems to negatively influence the redox status by the elevation of lipid peroxidation markers, protein carbonylation, and impairing erythrocyte antioxidant defense. However, other dialysis modalities do not so far appear to confer advantages. Supplementation with antioxidants might assist and should be considered as an early intervention to halt premature atherogenesis development at an early stage of CKD.
Intraoral osseous choristoma represents a benign lesion of growing ectopic bone in the soft tissues of the oral cavity. It is considered as rare entity while fewer than 100 cases have ever been ...reported worldwide. Nevertheless, the pathogenetic mechanism that drives this abnormal ossification still remains controversial. In the present study a case of lingual osseous choristoma in a 50-year old male is presented. The patient was treated with surgical excision and no recurrence was observed. In addition epidemiology, clinical presentation, and pathogenesis are reviewed, serving as a reminder of this rare pathology.
Osseous choristoma, osteoma, tongue.
Introduction and aims
Neurological complications such as peripheral neuropathy are very common in the end-stage renal disease (ESRD) patients, occurring in 60–80% of this specific population. The aim ...of the present study was to examine whether a 9-month hybrid intradialytic exercise training program could alter motor and sensory nerve conduction study (NCS) parameters in hemodialysis population.
Methods
Seventeen stable patients undergoing HD with no clinical evidence of uremic polyneuropathy were included in the study (15 M/2F, 59 ± 13.7 years). All patients completed a 9-month supervised exercise training program composed of both aerobic cycling and resistance training (hybrid) during HD. Functional capacity was assessed by a battery of tests, while pain levels and fatigue profile were assessed via validated questionnaires. Motor and sensory NCS on bilateral median, ulnar, peroneal and tibial nerves as well as F-wave were assessed using a full neurographic electromyography (EMG) assessment.
Results
After the 9-month exercise training intervention, exercise capacity was increased by 65% and functional capacity by an average of 40%. The neurological assessment showed that conduction velocity from tibial and peroneal nerves was improved by 3.7% and 4.2%, respectively, while tibial F-wave latency and peroneal and sural nerve distal latency were significantly improved by 4.2%, 4.9% and 10%, respectively. Fatigue and pain were improved after the exercise intervention while fatigue score was positively correlated with conduction velocity and amplitude values.
Conclusions
The results of the current study demonstrate that 9-month hybrid exercise training induces beneficial effects on both sensory and motor NCS parameters, improving conduction velocity and F-wave latency. Improvements in neural activity were accompanied by changes in fatigue score and pain-related aspects. The parallel improvement in motor nerve conduction velocity and its correlations with functional tests supports the hypothesis that exercise could be beneficial for preventing a decline in neural function in HD patients.
Purpose
Hemodialysis (HD) patients suffer from generalized weakness, exercise intolerance and muscle atrophy, all leading to generalized fatigue and lack of energy. HD patients spend at least 50% of ...their time in a functionally “switch off” mode with their fatigue sensations reaching a peak in the immediate hours after the dialysis session. The purpose of the current study was to assess the effectiveness of a nine-month hybrid intradialytic exercise program on fatigue symptoms occurring during and after hemodialysis session.
Methods
Twenty stable hemodialysis patients were included in the study (59 ± 13.7 years; 16 males). All patients completed a 9-month supervised exercise training program composed of both aerobic cycling and resistance training during HD. Aspects related to physical and generalized fatigue were assessed via validated questionnaires, while physical performance was assessed by a battery of tests, before and after the intervention period.
Results
Exercise capacity and physical performance were increased by an average of 65 and 40%, respectively. Patients reported feeling better during post-dialysis hours in question 1 (
p
= 0.000), question 3 (
p
= 0.009) and question 4 (
p
= 0.003) after the 9-month intervention. In addition, exercise training improved scores in cognitive function (
p
= 0.037), vitality (
p
= 0.05), depression (
p
= 0.000) and fatigue (
p
= 0.039).
Conclusion
The present study showed that a 9-month hybrid (aerobic + resistance) exercise training program improved symptoms of post-dialysis fatigue and overall general perception of fatigue. Hybrid exercise training is a safe and effective non-pharmacological approach to ameliorate fatigue symptoms in HD patients.
Trial registration number
Trial registration number The study is registered at ClinicalTrials.gov (NCT01721551, 2012) as a clinical trial.
Chronic kidney disease patients present with metabolic and functional muscle abnormalities, called uremic myopathy, whose mechanisms have not yet been fully elucidated. We investigated whether ...chronic renal insufficiency (CRI) affects skeletal muscle contractile properties at the cellular level. CRI was induced surgically in New Zealand rabbits (UREM), with sham-operation for controls (CON), and samples were collected at 3 months post-surgery, following euthanasia. All protocols had University Ethics approval following national and European guidelines. Sample treatments and evaluations were blinded. Maximal isometric force was assessed in 382 permeabilized psoas fibers (CON, n = 142, UREM, n = 240) initially at pH7, 10 °C (‘standard’ conditions), in subsets of fibers in acidic conditions (pH6.2, 10 °C) but also at near physiological temperature (pH7, 30 °C and pH6.2, 30 °C). CRI resulted in significant smaller average cross sectional areas (CSAs) by ∼11% for UREM muscle fibers (vs CON, P < 0.01). At standard conditions, UREM fibers produced lower absolute and specific forces (i.e. normalized force per fiber CSA) (vs CON, P < 0.01); force increased in 30 °C for both groups (P < 0.01), but the disparity between UREM and CON remained significant. Acidosis significantly reduced force (vs pH7, 10 °C P < 0.01), similarly in both groups (in UREM by −48% and in CON by −43%, P > 0.05). For the first time, we give evidence that CRI can induce significant impairments in single psoas muscle fibers force generation, only partly explained by fiber atrophy, thus affecting muscle mechanics at the cellular level.
Chronic kidney disease (CKD) is accompanied by a disturbed redox homeostasis, especially in end-stage patients, which is associated with pathological complications such as anemia, atherosclerosis, ...and muscle atrophy. However, limited evidence exists about redox disturbances before the end stage of CKD. Moreover, the available redox literature has not yet provided clear associations between circulating and tissue-specific (muscle) oxidative stress levels. The aim of the study was to evaluate commonly used redox status indices in the blood and in two different types of skeletal muscle (psoas, soleus) in the predialysis stages of CKD, using an animal model of renal insufficiency, and to investigate whether blood redox status indices could be reflecting the skeletal muscle redox status. Indices evaluated included reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), catalase (CAT), total antioxidant capacity (TAC), protein carbonyls (PC), and thiobarbituric acid reactive substances (TBARS). Results showed that blood GSH was higher in the uremic group compared to the control (17.50±1.73 vs. 12.43±1.01, p=0.033). In both muscle types, PC levels were higher in the uremic group compared to the control (psoas: 1.086±0.294 vs. 0.596±0.372, soleus: 2.52±0.29 vs. 0.929±0.41, p<0.05). The soleus had higher levels of TBARS, PC, GSH, CAT, and GR and lower TAC compared to the psoas in both groups. No significant correlations in redox status indices between the blood and skeletal muscles were found. However, in the uremic group, significant correlations between the psoas and soleus muscles in PC, GSSG, and CAT levels emerged, not present in the control. Even in the early stages of CKD, a disturbance in redox homeostasis was observed, which seemed to be muscle type-specific, while blood levels of redox indices did not seem to reflect the intramuscular condition. The above results highlight the need for further research in order to identify the key mechanisms driving the onset and progression of oxidative stress and its detrimental effects on CKD patients.
The aim of the current study was to examine whether prolonged low-intensity aerobic exercise could affect nocturnal activity in healthy individuals. Twenty-one healthy adults (24 ± 3.7 years; 9 ...females) were enrolled in this study. All participants participated in a 3-h low-intensity walking exercise protocol. Standard biochemical indices were assessed before the exercise protocol and at 72 h. Nocturnal activity and various indices of health were recorded for five consecutive days. The score of muscle pain peaked the night after the exercise protocol (
< 0.05) and returned to baseline two days after. No statistical differences were found in any of the parameters examined, including nocturnal activity. Prolonged low-intensity exercise does not affect nocturnal activity. The anecdotal reports suggesting that exercise or/and physical activity could worsen symptoms of motor restlessness during sleep in sleep disorders, such as restless legs syndrome and periodic limb movements, are not supported by this study. However, these findings need to be verified in clinical populations, as well as by using protocols with different forms of exercise.
Depression, a mental disorder with a high personal, societal, and economic impact, affects at least 20–30% of patients receiving hemodialysis therapy. It is associated with a high mortality rate, low ...adherence to medication, and a low perceived quality of life. Exercise training is a promising nonpharmacological intervention that can be safely applied to these patients. Beyond the well‐publicized physiological benefits of exercise training, a number of studies have focused on the effects of exercise training on mental factors and quality of life parameters including its less appreciated effects on depression symptoms. This evidence‐based review article reviews and discusses the effects of exercise training on depression in end‐stage renal disease patients.
Vaccination against rabies and routine antibody testing of subjects participating in programs for the surveillance and control of rabies in animals is strongly recommended. The scope of this study is ...to describe the antibody level as measured by a commercial enzyme-linked immunosorbent assay (ELISA) after primary and booster intramuscular vaccination with a purified vero-cell rabies vaccine (PVRV) in high-risk professionals and to determine the influence of an array of factors on antibody level, that is, time elapsed since primary immunization series and booster dose, sex, age, pathologic conditions, high-risk occupation, and peak antibody level after initial scheme and booster dose. A primary series of three doses of PVRV was administered and a commercial ELISA was recommended 14 days postimmunization with continuous repetition at 6 months and yearly intervals for the laboratory personnel and the rest of the professionals, respectively. The protective antibody titer was defined as a minimum of 0.5 equivalent units/mL (EU/mL) (seroconvertion) and a booster dose was applied if the titer was determined nonprotective. The seroconversion rate (SCR) after primary vaccination was 100%, with a geometric mean titer (GMT) of 2.90 EU/mL (interquartile range IQR: 1.85-3.45). After booster vaccination due to nonprotective titer, the SCR was 100% and the GMT increased by 678% (95% confidence interval CI: 514-887) reaching 4.25 EU/mL (IQR: 4.00-4.60), 2.5 times higher than the GMT elicited by the primary vaccine scheme in the respective recipients. The titer dropped by 1.20% per month (95% CI: 0.52-1.89) regardless of booster administration or any other factor. Women had 51% higher titer compared with men (95% CI: 6-116). High-risk professionals should be verified for adequate antibody titers, but routine administration of a single booster dose of PVRV 1 year after the primary series could be considered; more evidence is needed to support the benefit in terms of immunity and logistics.
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