Multidisciplinary integrated headache care: a prospective 12-month follow-up observational study

This prospective study investigated the effectiveness of a three-tier modularized out- and inpatient multidisciplinary integrated headache care program. N = 204 patients with frequent headaches (63 migraine, 11 tension-type headache, 59 migraine + tension-type headache, 68 medication-overuse headache and 3 with other primary headaches) were enrolled. Outcome measures at baseline, 6- and 12-month follow-ups included headache frequency, Migraine Disability Assessment (MIDAS), Hospital Anxiety and Depression Scale (HADS), standardized headache diary and a medication survey. Mean reduction in headache frequency was 5.5 ± 8.5 days/month, p < 0.001 at 6 months’ follow-up and 6.9 ± 8.3 days/month, p < 0.001 after 1 year. MIDAS decreased from 53.0 ± 60.8 to 37.0 ± 52.4 points, p < 0.001 after 6 months and 34.4 ± 53.2 points, p < 0.001 at 1 year. 44.0 % patients demonstrated at baseline an increased HAD-score for anxiety and 16.7 % of patients revealed a HAD-score indicating a depression. At the end of treatment statistically significant changes could be observed for anxiety (p < 0.001) and depression (p < 0.006). The intake frequency of attack-aborting medication decreased from 10.3 ± 7.3 days/month at admission to 4.7 ± 4.1 days/month, p < 0.001 after 6 months and reached 3.8 ± 3.5 days/month, p < 0.001 after 1 year. At baseline 37.9 % of patients had experience with non-pharmacological treatments and 87.0 % at 12-month follow-up. In conclusion, an integrated headache care program was successfully established. Positive health-related outcomes could be obtained with a multidisciplinary out- and inpatient headache treatment program.     

Effect of low-dose glucocorticoid on corticosteroid insufficient patients with acute exacerbation of chronic obstructive pulmonary disease

BACKGROUND: This study aimed to investigate the prevalence rate of critical illness-related corticosteroid insuffi ciency(CIRCI) and the effect of low-dose glucocorticoid on prognosis of CIRCI in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).METHODS: Since January 2010 to December 2012, 385 patients, who met the criteria of AECOPD, were enrolled in the Intensive Care Unit(ICU) of the First People's Hospital and Municipal Central Hospital of Xiangtan City. The AECOPD patients complicated with CIRCI screened by an adrenalcorticotrophic hormone test within 12 hours after admission to ICU were divided into a treatment group(n=32) and a control group(n=31) for a prospective, randomized and controlled clinical trial. Hydrocortisone(150 mg/d) or normal saline was injected intravenously for 7 days. The patients were followed up for 28 days after injection. The endpoint included 28-day survival time, non-shock time, ICU stay and the period of non-mechanical ventilation. The markers ofinfl ammation C-reactive protein, tumor necrosis factor-α, interleukin 6 and procalcitonin were measured at baseline and 7 days after treatment. The variables were analyzed by Student's t test, the non-parametric statistical test, the Chi-square test or the Kaplan-Meier method with SPSS18.0 statistic software. A P value 0.05 was considered statistically signifi cant.RESULTS: Totally 63 patients were diagnosed with CIRCI by an adrenalcorticotrophic hormone test and the prevalence rate was 16.4%. The shock rate of the AECOPD patients complicated with CIRCI was higher than that of the AECOPD patients without CIRCI(23.8% vs. 8.7%, P0.01). KaplanMeier analysis revealed that the 28-day survival time of the treatment group was obviously longer than that of the control group(P0.05). Compared with the control group, shock-free days within 28 days was longer in the treatment group(18.2±9.5 vs. 25.8±4.1, P0.05). Treatment with low-dose glucocorticoid obviously decreased the markers ofinfection and inflammation(P0.01), such as C-reactive protein(13.2±5.5 mg/L vs. 8.3±3.1 mg/L for the control group; 13.5±5.9 mg/L vs. 5.1±2.3 mg/L for the treatment group), tumor necrosis factor-α(26.1±16.2 g/L vs. 17.5±11.7 g/L for the control group; 25.0±14.8 g/L vs. 10.4±7.8 g/L for the treatment group) and procalcitonin(3.88 g/L vs. 2.03 g/L for the control group; 3.77 g/L vs. 1.26 g/L for the treatment group). Furthermore, the markers in the treatment group decreased more obviously than those in the control group(P0.01).CONCLUSION: The prevalence rate of CIRCI was higher in the patients with AECOPD in the department of critical medicine, and low-dose glucocorticoid treatment for one week reduced the 28-day mortality, shock time and markers ofinfection and infl ammation.     

Relationship between the cAMP levels in leukocytes and the cytokine balance in patients surviving gram negative bacterial pneumonia

Lipopolysaccharide-stimulated leukocytes secrete proinflammatory cytokines including tumor necrosis factor-α and interleukin-12. Over-activation of host defense systems may result in severe tissue damage and requires regulation. Granulocyte colony-stimulating factor and interleukin-10 are candidate cytokines for inducing tolerance to lipopolysaccharide re-stimulation. We compared cytokines secreted by lipopolysaccharide-stimulated blood cells from patients who had survived gram negative bacterial pneumonia (Pseudomonas aeruginosa, Escherichia coli or Proteus mirabilis, n = 26) and age-matched healthy volunteers (n = 18). Interleukin-12p70 and tumor necrosis factor-α expression was significantly lower in patients (p = 0.0039 and p<0.001) compared to healthy controls, while granulocyte colony-stimulating factor production was markedly higher in patients (p<0.001). Levels of interleukin-10 were comparable. Granulocyte colony-stimulating factor expression was inversely correlated with interleukin-12p70 (R = −0.71, p<0.001) and tumor necrosis factor-α (R = −0.64, p<0.001) expression; interleukin-10 showed no significant correlation. In unstimulated leukocytes from patients, cAMP levels were significantly raised (p = 0.020) and were correlated inversely with interleukin-12p70 levels (R = −0.81, p<0.001) and directly with granulocyte colony-stimulating factor (R = 0.72, p = 0.0020), matrix metalloproteinase-9 (R = 0.67, p = 0.0067) and interleukin-10 (R = 0.54, p = 0.039) levels. Our results demonstrate that granulocyte colony-stimulating factor production by lipopolysaccharide-stimulated leukocytes is a useful indicator of tolerance induction in surviving pneumonia patients and that measuring cAMP in freshly isolated leukocytes may also be clinically significant.     

Cardiac injury is associated with inflammation in geriatric COVID‐19 patients

BackgroundGeriatric patients with coronavirus disease (COVID‐19) are at high risk of developing cardiac injury. Identifying the factors that affect high‐sensitivity cardiac troponin I may indicate the cause of cardiac injury in elderly patients, and this could hopefully assist in protecting heart function in this patient population.MethodsOne hundred and eighty inpatients who were admitted for COVID‐19 were screened. Patients older than 60 years were included in this study, and the clinical characteristics and laboratory results of the cohort were analyzed. The correlation between cardiac injury and clinical/laboratory variables was statistically analyzed, and further logistic regression was performed to determine how these variables influence cardiac injury in geriatric patients.ResultsAge (p < 0.001) significantly correlated with cardiac injury, whereas sex (p = 0.372) and coexisting diseases did not. Rising procalcitonin (p = 0.001), interleukin‐2 receptor (p < 0.001), interleukin 6 (p = 0.001), interleukin 10 (p < 0.001), tumor necrosis factor α (p = 0.001), high‐sensitivity C‐reactive protein (p = 0.001), D‐dimer (p < 0.001), white blood cells (p < 0.001), neutrophils (p = 0.001), declining lymphocytes (p < 0.001), and natural killer cells (p = 0.005) were associated with cardiac injury and showed predictive ability in the multivariate logistic regression.ConclusionOur results suggest that age and inflammatory factors influence cardiac injury in elderly patients. Interfering with inflammation in this patient population may potentially confer cardiac protection.     

The daily response for proton pump inhibitor treatment in Japanese reflux esophagitis and non-erosive reflux disease

We investigated comparison according to reflux esophagitis and non-erosive reflux disease about “daily” symptom improvement for proton pump inhibitor treatment. We enrolled 57 reflux esophagitis and 90 non-erosive reflux disease patients. They took rabeprazole 10 mg/day for 28 days and completed “daily” in the Frequency Scale for the Symptoms of GERD from baseline until day 14, and after 28 days of treatment. The efficacy endpoint was the improvement rates in Frequency Scale for the Symptoms of GERD, based on baseline. Frequency Scale for the Symptoms of GERD was decreased in reflux esophagitis and non-erosive reflux disease (p<0.001) and was significantly lower in reflux esophagitis than in non-erosive reflux disease from the first day of treatment (p<0.05). Symptomatic improvement rates were also significantly higher in reflux esophagitis (50.3 ± 44.9%) than in non-erosive reflux disease (31.7 ± 43.2%) from the first day of treatment (p<0.0001). The symptomatic improvement rates in reflux esophagitis were significant increased from the second day of treatment until after 28 days of treatment (p = 0.0006), however, these in non-erosive reflux disease were significant increased from third days until after 28 days of treatment (p = 0.0002). In non-erosive reflux disease, the improvement of dysmotility symptom was particularly gradual as well as of reflux symptom, too. As for results of prediction of proton pump inhibitor response (completed symptom resolution) form early symptom improvement within 1 week, it was able to predict proton pump inhibitor response from the symptom improvement rate on 3 days in reflux esophagitis and on day 7 in non-erosive reflux disease. In conclusion, the prediction of the proton pump inhibitor response in non-erosive reflux disease was slow in comparison with reflux esophagitis. The cause was gradual improvement of dysmotility symptom.     

Relationship between dietary folate intake and plasma monocyte chemoattractant protein-1 and interleukin-8 in heart failure patients

This study aimed to examine the association of dietary vitamin intakes with plasma pro-inflammatory cytokine levels in Korean heart failure patients. Stable outpatients with heart failure were recruited and finally 91 patients were included. Dietary intakes were estimated by a developed semi-quantitative food frequency questionnaire. The simultaneous measurement of 17 cytokines was performed along with analysis of plasma C-reactive protein. Plasma C-reactive protein levels significantly correlated with dietary intakes of vitamin C (r = −0.30, p<0.005), β-carotene (r = −0.23, p<0.05), and folate (r = −0.31, p<0.005). However, these associations were no longer significant after adjusting for traditional risk factors for heart failure. On the other hand, plasma levels of monocyte chemoattractant protein-1 significantly correlated with dietary folate intake (r = −0.31, p<0.001), and plasma interleukin-8 levels significantly correlated with dietary intakes of vitamin C (r = −0.38, p<0.001), β-carotene (r = –0.42, p<0.001), and folate (r = −0.38, p<0.001) after the adjustment. Dietary folate intake was found as a primary influencing factor on plasma levels of monocyte chemoattractant protein-1 (p<0.005, R² = 0.20) and interleukin-8 (p<0.001, R² = 0.32) through a stepwise multiple linear regression analysis. Dietary folate intake was significantly associated with plasma levels of monocyte chemoattractant protein-1 and interleukin-8 which indicates dietary folate may have a potentially beneficial role in the prevention and treatment of heart failure.     

Is administrating branched-chain amino acid-enriched nutrition achieved symptom-free in malnourished cirrhotic patients?

Administration of branched-chain amino acids (BCAA) has been reported to improve liver function, quality of life (QOL). However, in some malnourished patients, serum albumin levels do not improve in response to BCAA granules. In this study, we examined the effects of BCAA-enriched enteral nutrition in patients unresponsive to BCAA granules. Thirty-two decompensated cirrhotic patients at Osaka Medical College were enrolled in this study. Since all patients showed no improvement in serum albumin levels despite 3 months of BCAA granule administration, they were administered 50 g of a flavored BCAA-enriched enteral nutrient twice daily, i.e., during the daytime and late evening. Serum albumin levels and major cirrhotic symptoms were examined 1, 3, and 5 months after treatment initiation. Serum albumin levels improved significantly 3 months after treatment initiation (3.14 ± 0.32 g/dl vs 3.5 ± 0.31 g/dl, p<0.01), and Child–Pugh scores decreased significantly (p<0.01). In the majority (53–80%) of patients, muscles cramps, fatigue, fatigability, edema, and sleep disturbance improved within 3 months after therapy initiation. Moreover, approximately 90% of the patients became symptom-free 5 months after treatment initiation. These results indicate that switching to BCAA-enriched nutrients improves QOL of cirrhotic patients unresponsive to BCAA granules.     

Drug-dependence behaviour and outcome of medication-overuse headache after treatment

This study aimed at determining the causes of failure of the different proposed strategies to ensure improvement of medication-overuse headache (MOH) patients, since they have not been investigated so far, especially with regard to aspects related to cognitive and behavioural aspects of symptomatic drugs overused by them. One hundred and twenty in-patients, 82 females (68.3 %), median age 49 (42–56) years, affected by MOH were admitted to the study and treated with abrupt discontinuation of the medication overused, a 6-day in-patient detoxification regimen and an immediate start of personalized prophylactic treatment, then followed for 1 year. Leeds Dependence Questionnaire (LDQ), among all the clinical variables, was administered at baseline and at 1-year follow-up visit to assess substance dependence. Of the 120 patients enrolled, 68 (56.7 %) were successfully detoxified (Responder-group), while 52 (43.3 %) were not (Non-Responder-group). At baseline, the mean LDQ total score was slightly higher in the Non-Responder group than in the Responder group (12.08 ± 2.14 vs. 11.94 ± 1.98). Although this difference was not significant at baseline (p > 0.05), the LDQ total score was significantly different (p < 0.001) at the 1-year follow-up visit between the responder group (7.8 ± 2.3) and the Non-Responder group (12.1 ± 2.1). Moreover, the pattern of the responses of the patients in the responder group differed from that of the Non-Responder-group in the items relating to the compulsion to start, compulsion to continue, primacy of effect, constancy of state and cognitive set. The results showed that patients of the Non-Responder group showed a drug dependence pattern similar to that previously described in addicts. Conversely, in patients who positively responded to the procedure, drug-abuse behaviour seemed to be a consequence of chronic headache, reflecting the need for daily analgesic use to cope with everyday life.     

Relationship between the estimates of desaturase activities and cardiometabolic phenotypes in Koreans

In the present study, we evaluated the relationships of estimated desaturase activities with cardiometabolic risk factors including abdominal obesity, atherogenic lipoprotein phenotype and inflammation in Koreans. Ninety-three healthy volunteers participated in this cross-sectional study. LDL particle size was determined using gradient gel electrophoresis and inflammatory markers including C-reactive protein, soluble intercellular adhesion molecule-1, and adiponectin were measured. Stearoyl–coA desaturase, delta-6 desaturase and delta-5 desaturase were estimated as precursor to fatty acid ratios. The results showed that stearoyl–coA desaturase was correlated with body mass index (r = 0.235, p<0.05), triglyceride (r = 0.261, p<0.001), and HDL-cholesterol (r = −0.226, p<0.05). Stearoyl–coA desaturase was associated with only triglyceride (r = 0.283, p<0.01). Delta-6 desaturase was correlated with body mass index (r = 0.236, p<0.05), waist circumference (r = 0.218, p<0.05), triglyceride (r = 0.399, p<0.001), C-reactive protein (r = 0.333, p<0.001), soluble intercellular adhesion molecule-1 (r = 0.229, p<0.05), HDL-cholesterol (r = −0.325, p<0.01), LDL particle size (r = −0.297, p<0.01) and adiponectin (r = −0.233, p<0.05). In contrast, delta-5 desaturase was correlated with body mass index (r = −0.324, p<0.01), waist circumference (r = −0.276, p<0.01), triglyceride (r = −0.329, p<0.01), C-reactive protein (r = −0.215, p<0.05), HDL-cholesterol (r = 0.262, p<0.05) and LDL particle size (r = 0.278, p<0.01). Stepwise multiple regression analysis revealed that delta-6 desaturase (p<0.01) together with waist circumference (p<0.001) were found to be independent factors for determining plasma levels of C-reactive protein (R² = 0.230). Estimated desaturase activities are closely associated with the features of cardiometabolic risk in Koreans.     

Restoration of hypoglycemia awareness after islet transplantation

OBJECTIVE—To determine the impact of islet transplantation (ITx) on hypoglycemia awareness in patients with unstable type 1 diabetes and its relation to islet function.RESEARCH DESIGN AND METHODS—A total of 31 ITx recipients were studied. Hypoglycemia unawareness was assessed using the Clarke hypoglycemic score (0 = no hypoglycemia; ≥4 = hypoglycemia unawareness). Subjects were grouped based on graft function: off-insulin (n = 8), graft dysfunction (on-insulin and stimulated C-peptide ≥0.3 ng/ml, n = 13), and graft failure (stimulated C-peptide <0.3 ng/ml, n = 10, evaluated 11.5 ± 14.5 months after graft failure).RESULTS—The hypoglycemia score improved after ITx when compared with baseline values (before vs. after: 5.29 ± 1.51 vs. 1.35 ± 1.92, P < 0.001). This result was sustained even after patient stratification based on islet function (pre vs. post off-insulin: 5.63 ± 2.00 vs. no hypoglycemia reported; graft dysfunction: 5.31 ± 1.49 vs. 1.15 ± 1.63, P < 0.001; and graft failure: 5.00 ± 1.16 vs. 2.70 ± 2.26, P = 0.014).CONCLUSIONS—The improved metabolic control achieved with ITx can restore hypoglycemia awareness in patients with type 1 diabetes, persisting even after islet graft failure.Occurrence of hypoglycemia is the major limitation of intensive control aimed at A1C normalization in patients with type 1 diabetes. Frequent hypoglycemic episodes are particularly common in subjects with unstable type 1 diabetes and can lead to hypoglycemia unawareness. Although islet transplantation (ITx) prevents severe hypoglycemia (1) and restores some counterregulatory hormone secretion (2), data showing its effects on restitution of hypoglycemia awareness are not conclusive (2,3).The aim of this study was to determine if the optimal metabolic control achieved by ITx can restore hypoglycemia awareness and whether or not these effects persist after islet graft failure.     

Evaluation of Aortic Elasticity Parameters in Survivors of COVID-19 Using Echocardiography Imaging

ObjectiveWhile severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects lung tissue, it may cause direct or indirect damage to the cardiovascular system, and permanent damage may occur. Arterial stiffness is an early indicator of cardiovascular disease risk. The aim of our study was to establish the potential effects of SARS-CoV-2 on the vascular system evaluated by transthoracic echocardiographic examination.Subjects and MethodsThis study compared arterial stiffness between the survivors of COVID-19 and those without a history of COVID-19 infection. The difference in aortic diameter was examined using echocardiography.ResultsThe study included 50 patients who survived COVID-19 in the last 3–6 months and 50 age- and gender-matched healthy volunteers. In surviving COVID-19 patients, aortic diastolic diameter in cm ([3.1 ± 0.2] vs. [2.9 ± 0.1], p < 0.001), pulse pressure (PP) ([43.02 ± 14.05] vs. [35.74 ± 9.86], p = 0.004), aortic distensibility ([5.61 ± 3.57] vs. [8.31 ± 3.82], p < 0.001), aortic strain ([10.56 ± 4.91] vs. [13.88 ± 5.86], p = 0.003), PP/stroke volume index ([1.25 ± 0.47] vs. [0.98 ± 0.28], p = 0.001), and aortic stiffness index ([2.82 ± 0.47] vs. [2.46 ± 0.45], p < 0.001) were statistically significant compared to the control group.ConclusionSARS-CoV-2 may cause reduced or impaired aortic elasticity parameters linked to impaired arterial wall function in COVID-19 survivors compared with controls.     

The relation of common inflammatory cytokines with anxiety and depression and their values in estimating cardiovascular outcomes in coronary heart disease patients

BackgroundInflammatory cytokines are associated with the occurrence and severity of psychological disorders in cerebro‐cardiovascular disease patients. This study aimed to investigate the correlation of inflammatory cytokines with anxiety and depression in coronary heart disease (CHD) patients and their values for estimating cardiovascular outcomes.MethodsTotally, 150 CHD patients and 50 healthy subjects were enrolled. Then, tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, IL‐10, and IL‐17 in their serum samples were detected using ELISA assay; anxiety and depression were assessed by the HADS score. For CHD patients, major adverse cardiac events (MACE) were recorded and evaluated.ResultsCHD patients presented with increased TNF‐α (median: 50.0 vs. 37.0 pg/ml, p < 0.001), IL‐1β (median: 2.7 vs. 2.0 pg/ml, p < 0.001), IL‐6 (median: 24.7 vs. 24.3 pg/ml, p = 0.032), IL‐17A (median: 58.6 vs. 43.6 pg/ml, p < 0.001), HADS‐A score (p < 0.001), HADS‐D score (p < 0.001), anxiety rate (p < 0.001), and depression rate (p < 0.001) compared to healthy subjects. Then, TNF‐α (p = 0.003), IL‐1β (p = 0.023), and IL‐17A (p < 0.001) were related to elevated HADS‐A score. Also, TNF‐α (p = 0.014) and IL‐17A (p = 0.020) positively, while IL‐10 (p = 0.047) negatively related to the HADS‐D score in CHD patients. Interestingly, elevated TNF‐α and IL‐17A were associated with anxiety and depression occurrence in CHD patients (all p < 0.05). Inspiringly, only TNF‐α high, but not other cytokines, was related to elevated accumulating MACE (p = 0.041), while no correlation of anxiety (p = 0.173) or depression (p = 0.068) with accumulating MACE was observed.ConclusionTNF‐α and IL‐17A correlate with anxiety and depression, while only TNF‐α high is related to elevated accumulating MACE in CHD patients.     

Multiple free-radical scavenging capacity in serum

We have developed a method to determine serum scavenging-capacity profile against multiple free radical species, namely hydroxyl radical, superoxide radical, alkoxyl radical, alkylperoxyl radical, alkyl radical, and singlet oxygen. This method was applied to a cohort of chronic kidney disease patients. Each free radical species was produced with a common experimental procedure; i.e., uv/visible-light photolysis of free-radical precursor/sensitizer. The decrease in free-radical concentration by the presence of serum was quantified with electron spin resonance spin trapping method, from which the scavenging capacity was calculated. There was a significant capacity change in the disease group (n = 45) as compared with the healthy control group (n = 30). The percent values of disease’s scavenging capacity with respect to control group indicated statistically significant differences in all free-radical species except alkylperoxyl radical, i.e., hydroxyl radical, 73 ± 12% (p = 0.001); superoxide radical, 158 ± 50% (p = 0.001); alkoxyl radical, 121 ± 30% (p = 0.005); alkylperoxyl radical, 123 ± 32% (p>0.1); alkyl radical, 26 ± 14% (p = 0.001); and singlet oxygen, 57 ± 18% (p = 0.001). The scavenging capacity profile was illustrated using a radar chart, clearly demonstrating the characteristic change in the disease group. Although the cause of the scavenging capacity change by the disease state is not completely understood, the profile of multiple radical scavenging capacities may become a useful diagnostic tool.     

A double-blind, randomized, multicenter, Italian study of frovatriptan versus rizatriptan for the acute treatment of migraine

The objective of this study was to assess patient satisfaction with acute treatment of migraine with frovatriptan or rizatriptan by preference questionnaire. 148 subjects with a history of migraine with or without aura (IHS 2004 criteria), with at least one migraine attack per month in the preceding 6 months, were enrolled and randomized to frovatriptan 2.5 mg or rizatriptan 10 mg treating 1–3 attacks. The study had a multicenter, randomized, double-blind, cross-over design, with treatment periods lasting <3 months. At the end of the study, patients assigned preference to one of the treatments using a questionnaire with a score from 0 to 5 (primary endpoint). Secondary endpoints were pain-free and pain relief episodes at 2 h, and recurrent and sustained pain-free episodes within 48 h. 104 of the 125 patients (83%, intention-to-treat population) expressed a preference for a triptan. The average preference score was not significantly different between frovatriptan (2.9 ± 1.3) and rizatriptan (3.2 ± 1.1). The rates of pain-free (33% frovatriptan vs. 39% rizatriptan) and pain relief (55 vs. 62%) episodes at 2 h were not significantly different between the two treatments. The rate of recurrent episodes was significantly (p < 0.001) lower under frovatriptan (21 vs. 43% rizatriptan). No significant differences were observed in sustained pain-free episodes (26% frovatriptan vs. 22% rizatriptan). The number of patients with adverse events was not significantly different between rizatriptan (34) and frovatriptan (25, p = NS). The results suggest that frovatriptan has a similar efficacy to rizatriptan, but a more prolonged duration of action.

Electronic supplementary material

The online version of this article (doi:10.1007/s10194-010-0243-y) contains supplementary material, which is available to authorized users.     

Close to recommended caloric and protein intake by enteral nutrition is associated with better clinical outcome of critically ill septic patients: secondary analysis of a large international nutrition database

Introduction

Current international sepsis guidelines recommend low-dose enteral nutrition (EN) for the first week. This contradicts other nutrition guidelines for heterogenous groups of ICU patients. Data on the optimal dose of EN in septic patients are lacking. Our aim was to evaluate the effect of energy and protein amount given by EN on clinical outcomes in a large cohort of critically ill septic patients.

Methods

We conducted a secondary analysis of pooled data collected prospectively from international nutrition studies. Eligible patients had a diagnosis of sepsis and/or pneumonia and were admitted to the ICU for ≥3 days, mechanically ventilated within 48 hours of ICU admission and only receiving EN. Patients receiving parenteral nutrition were excluded. Data were collected from ICU admission up to a maximum of 12 days. Regression models were used to examine the impact of calorie and protein intake on 60-day mortality and ventilator-free days.

Results

Of the 13,630 patients included in the dataset, 2,270 met the study inclusion criteria. Patients received a mean amount of 1,057 kcal/d (14.5 kcal/kg/day) and 49 g protein/day (0.7 g/kg/d) by EN alone. Patients were mechanically ventilated for a median of 8.4 days and 60-day mortality was 30.5%. An increase of 1,000 kcal was associated with reduced 60-day mortality (odds ratio (OR) 0.61; 95% confidence interval (CI) 0.48 to 0.77, P <0.001) and more ventilator-free days (2.81 days, 95% CI 0.53 to 5.08, P = 0.02) as was an increase of 30 g protein per day (OR 0.76; 95% CI 0.65 to 0.87, P <0.001 and 1.92 days, 95% CI 0.58 to 3.27, P = 0.005, respectively).

Conclusions

In critically ill septic patients, a calorie and protein delivery closer to recommended amounts by EN in the early phase of ICU stay was associated with a more favorable outcome.     

Correlation between symptomatic improvement and quality of life in patients with reflux and dyspeptic symptoms

We investigated the correlation between symptomatic improvement and quality of life in Japanese gastroesophageal reflux disease patients with PPI. Eighty one patients with reflux and dyspeptic symptom were enrolled. The evaluation of the symptom was used he Frequency Scale for the Symptom of GERD in 3 categories: total score of 12 questions, score related to reflux symptoms, and score related to dyspeptic symptoms and the evaluation of the quality of life was use the 8-item Short Form Health Survey in 2 categories, the physical component summary score and mental component summary score. All patients administered rabeprazole 10 mg/day for 8 weeks. We investigated the correlation between symptomatic improvement with proton pump inhibitor and quality of life. Significant symptomatic improvement was seen in the total score of 12 questions (26.7 ± 8.8 → 17.5 ± 5.9, p<0.0001), score related to reflux symptoms (14.9 ± 5.4 → 9.6 ± 3.6, p<0.0001), and score related to dyspeptic symptoms (11.8 ± 4.3 → 8.0 ± 2.9, p<0.0001). Significant improvement in quality of life was seen in the physical component summary score (47.8 ± 6.6 → 50.0 ± 5.9, p = 0.0209) and mental component summary score (47.4 ± 8.5 → 50.4 ± 5.3, p = 0.0133) with proton pump inhibitor. With proton pump inhibitor, a significant positive correlation was seen between the improvement rates in total score of 12 questions, score related to dyspeptic symptoms and in mental component summary score at 8 weeks (total score of 12 questions: r = 0.275, p = 0.0265, score related to dyspeptic symptoms: r = 0.367, p = 0.0027). In conclusion, quality of life was associated with improvement in dyspeptic symptoms with proton pump inhibitor treatment.     

Probiotics ameliorates glycemic control of patients with diabetic nephropathy: A randomized clinical study

ObjectiveThis research aimed to explore the effects of probiotic administration on glycemic control and renal function in patients with diabetic nephropathy (DN).MethodsThe 101 participants were randomly divided into two treatment groups and 76 patients were included in the final analysis. In 76 patients with diabetic nephropathy of type 2 diabetes, a randomized double‐blind and placebo‐controlled clinical trial was conducted to evaluate the administration of 3.2 × 10⁹ CFU probiotic supplements per day (Bifidobacterium bifidum, 1.2 × 10⁹ CFU, Lactobacillus acidophilus 4.2 × 10⁹ CFU, Streptococcus thermophilus 4.3 × 10⁹ CFU) for 12 weeks on glycemic control of patients, including fasting blood glucose, 2 h postprandial blood glucose, glycosylated hemoglobin (HbA1c), microalbuminuria/creatinine (mAlb/Cr) and estimated glomerular filtration rate (eGFR) levels. The placebo group daily received empty capsules filled with starch.ResultsAfter 12 weeks, the administration of probiotics demonstrated a significant reduction in fasting blood glucose (10.68 ± 3.24 mmol/L before vs. 7.81 ± 2.77 mmol/L after, p < 0.05), HbA1c (8.19 ± 1.60% before vs. 7.32 ± 1.20% after, p < 0.05) and mAlb/Cr (101.60 ± 22.17 mg/g before vs. 67.53 ± 20.11 mg/g after, p < 0.05), while only mAlb/Cr level was significantly lower in the probiotic group than in the placebo group after intervention (67.53 ± 20.11 mg/g vs. 87.71 ± 23.01, p < 0.05). Meanwhile, there was no significant reduction of 2 h postprandial blood glucose level (18.95 ± 5.23 mmol/L vs. 17.35 ± 6.28 mmol/L, p = 0.24) and eGFR (84.34 ± 6.97 ml/min vs. 82.8 ± 8.72 ml/min, p = 0.45) in patients before and after probiotic intake. In addition, the placebo group failed to show any significant change of these parameters.ConclusionThis clinical study revealed probiotic administration could ameliorate glycemic control of patients with diabetic nephropathy, potentiating its therapeutic potential in clinical application.     

The effect of B vitamin supplementation on wound healing in type 2 diabetic mice

The aim of this study was to test the effects of B-group vitamin supplements on wound healing in diabetic mice. The mice in the experimental group were treated daily with 1 g/L B₆, 1.25 mg/L B₁₂, and 62.5 mg/L folic acid in their drinking water. Full-thickness excision wounds were created with 6-mm skin biopsy punches. Each wound closure was digitally photographed. Beginning on day 3 after wounding, the wound area in the diabetic mice was statistically larger than that of normal mice (p<0.05 vs diabetic mice). The diabetic mice treated with B vitamins displayed accelerated wound closure on day 3 (wound area 42.8 ± 11.3%, p<0.05). On day 9 after wounding, the wound area in the diabetic mice was also statistically larger than that of normal mice (p<0.05 vs diabetic mice). The diabetic mice treated with B vitamins displayed accelerated wound closure on day 3 (wound area 13.2 ± 16.8%, p<0.05). In addition, the high glucose level in the diabetic animals decreased significantly in response to B vitamin treatment. In conclusion, the results of this study indicate that B vitamin supplementation may improve wound healing in diabetic mice.     

Role of Plasma Vasopressin in Impaired Water Excretion of Glucocorticoid Deficiency

In the present study, the effect of selective glucocorticoid deficiency on renal water excretion was investigated in conscious, trained, adrenalectomized dogs. The animals were studied before and after a water load while on replacement therapy of desoxycorticosterone acetate, 5 mg/day, and dexamethasone, 0.8 mg/day (group I), and while off dexamethasone for 5-9 days (group II). Before the water load the weight, inulin space, cardiac output, blood pressure, glomerular filtration rate, renal blood flow, plasma osmolality, and plasma antidiuretic hormone measured by radioimmunoassay were similar in both groups I and II. However, after a 40 ml/kg water load a marked impairment in renal water excretion in the glucocorticoid deficient dogs became apparent. Maximal free water clearance was −0.046±0.16 vs. 6.51±0.72 ml/min (P < 0.001) and minimal urinary osmolality was 425±56 vs. 82±3.5 mosmol/kg H₂O (P < 0.001) in group II as compared to group I. Plasma antidiuretic hormone was maximally suppressed during the water load in group I to 0.34±0.08 pg/ml but remained elevated at 9.18±1.79 pg/ml (P < 0.005) in group II. This nonsuppressibility of plasma antidiuretic hormone during water loading in group II was associated with a significant tachycardia of 145±6 vs. 87±6 beats/min (P < 0.001) in group I and a significantly lower stroke volume of 27±0 vs. 59±0.5 ml/beat (P < 0.001). In conclusion, our results implicate a persistent secretion of antidiuretic hormone as an important factor in the impaired water excretion of glucocorticoid deficiency. A deleterious effect of glucocorticoid deficiency on cardiac function was observed and this hemodynamic alteration could be involved in initiating a nonosmolar, baroreceptor-mediated release of vasopressin.     

Effect of Renin-Angiotensin System Blockade on Insulin Resistance and Inflammatory Parameters in Patients With Impaired Glucose Tolerance

OBJECTIVE

The study investigated the effect of angiotensin receptor blockers (ARB) on glucose homeostasis and inflammatory parameters in patients with impaired glucose tolerance (IGT).

RESEARCH DESIGN AND METHODS

We prospectively studied the insulin sensitivity index (ISI) and homeostasis model assessment–insulin resistance (HOMA-IR) in 13 obese males with IGT and in 13 matched control subjects with normal glucose tolerance (NGT) during hyperglycemic testing over 90 min. Adiponectin, retinol-binding protein 4 (RBP4), and high-sensitive C-reactive protein (hsCRP) were analyzed. Measurements were performed at baseline and after a 4-week treatment with 160 mg/day valsartan. The results of the IGT and NGT groups were compared.

RESULTS

At baseline, HOMA-IR (IGT 4.1 ± 3 vs. NGT 2.3 ± 1.0, P < 0.01), hsCRP (IGT 3.9 ± 1.9 vs. NGT 1.8 ± 1 mg/l, P < 0.05), and RBP4 (IGT 27.1 ± 2.1 vs. NGT 24.0 ± 2.0 ng/ml, P < 0.05) were significantly higher, whereas ISI (IGT 1.5 ± 0.9 vs. NGT 1.8 ± 1.2, P < 0.05) and plasma adiponectin (IGT 3.2 ± 0.9, NGT 5.2 ± 2.4 μg/ml, P < 0.05) were significantly lower in the IGT group compared with the NGT group. Under ARB, there was an increase in both groups of adiponectin (IGT 4.1 ± 1.9 μg/ml, NGT 6.3 ± 2.9 μg/ml, P < 0.05) and an increase in ISI (IGT 1.5 ± 0.9 to 2.3 ± 1 μg/ml, NGT 1.8 ± 1 to 2.5 ± 2 μg/ml, P < 0.05). HOMA-IR (4.1 ± 3 to 2.6 ± 2; P < 0.01), hsCRP (3.9 ± 1.9 to 1.8 ± 1 mg/l, P < 0.05), and RBP4 (27.1 ± 2.1 to 22.1 ± 1.8 ng/ml, P < 0.01) decreased significantly in the IGT group.

CONCLUSIONS

Insulin sensitivity and associated inflammatory factors improve under ARB in IGT patients.Insulin resistance has a causal role in type 2 diabetes, a crucial risk factor for cardiovascular and renal disease (1). Impaired glucose tolerance (IGT) represents an intermediate state of abnormal glucose regulation between normal glucose homeostasis and manifest diabetes. IGT is defined as elevated 2-h plasma glucose concentration >140 and <200 mg/dl after a 75-g oral glucose load in an oral glucose tolerance test (2). A combination of β-cell dysfunction and insulin resistance with decreased insulin sensitivity or responsiveness to the metabolic action of insulin plays a pathogenetic role. Insulin resistance is common in subjects with visceral adiposity, hypertension, hyperglycemia, and dyslipidemia. Patients with metabolic syndrome have a high risk of developing frank diabetes (3).Adiponectin is a fat-derived hormone specifically produced and secreted by adipocytes. This adipocytokine is considered an important modulator of insulin sensitivity in patients with IGT (4,5). Adiponectin levels decrease in the obese, which may be a contributing factor to insulin resistance. Anti-inflammatory properties also have been attributed to adiponectin. This is indicated by serum concentrations of adiponectin, which are inversely associated with inflammatory markers such as C-reactive protein (CRP). Retinol-binding protein 4 (RBP4) is another adipocyte-secreted molecule and is elevated in serum before development of overt diabetes (6).The interaction of these different metabolic and inflammatory parameters in IGT has not been fully clarified. Our study investigates insulin sensitivity and associated risk factors focusing on obese subjects with IGT. We tested the effect of a short-term 4-week angiotensin receptor blocker (ARB) treatment on glucose disposal and inflammatory markers in subjects with IGT.