Ultrafiltration is better than diuretic therapy for volume-overloaded acute heart failure patients: a meta-analysis.

Studies on the effectiveness of ultrafiltration (UF) in patients hospitalized with acute decompensated heart failure (ADHF) have led to heterogeneous study outcomes. This meta-analysis aimed to assess the impact of UF therapy in ADHF patients. We searched the medical literature to identify well-designed studies comparing UF with the usual diuretic therapy in this setting. Systematic evaluation of 8 randomized controlled trials enrolling 801 participants showed greater fluid removal (difference in means 1372.5 mL, 95% CI 849.6 to 1895.4 mL; p < 0.001), weight loss (difference in means 1.592 kg, 95% CI 1.039 to 2.144 kg; p < 0.001) and lower incidences of worsening heart failure (OR 0.63, 95% CI 0.43 to 0.94, p = 0.022) and rehospitalization for heart failure (OR 0.54, 95% CI 0.36 to 0.82, p = 0.003) without a difference in renal impairment (OR 1.386, 95% CI 0.870 to 2.209; p = 0.169) or all-cause mortality (OR 1.13, 95% CI 0.75 to 1.71, p = 0.546). UF increases fluid removal and weight loss and reduces rehospitalization and the risk of worsening heart failure in congestive patients, suggesting ultrafiltration as a safe and effective treatment option for volume-overloaded heart failure patients.

The quadrivalent HPV vaccine is protective against genital warts: a meta-analysis.

BACKGROUND: The quadrivalent human papillomavirus (HPV) vaccine has been assumed to give protection against genital warts (GW) as well as cervical cancer. Our main question was whether HPV vaccine has any effects on the prevention of GW reported in randomised controlled clinical trials (RCTs) and time-trend analyses. METHODS: This meta-analysis was performed according to the PRISMA guidelines using the PICO format. We searched in three electronic databases (PubMed, Embase, Cochrane Trials), and assessed heterogeneity using the Q-test and I-squared statistics, meta-regression was also performed. Odds ratios (OR) and their confidence intervals (CI) were calculated. The sensitivity was tested by leave-one-out method. We evaluated the presence of publication bias using the funnel plot graph and the Copas selection model. The strength of evidence was assessed using the GRADE approach. RESULTS: Eight RCTs (per-protocol populations) and eight time-trend ecological studies were included in this meta-analysis. A significant reduction (pooled OR = 0.03, 95% CI: 0.01-0.09; I-squared = 53.6%) of GW in young women was recorded in RCTs, and in time-trend analyses both in young women (pooled OR = 0.36, CI 95% = 0.26-0.51; I-squared = 98.2%), and in young men (pooled OR = 0.69, 95% CI = 0.61-0.78; I-squared = 92.7%). In subgroup analysis, a significant reduction of the number of GW events was observed especially in women under 21 years (pooled OR = 0.33, 95% CI = 0.17-0.63). Leave-one-out analysis showed that similar results could be obtained after excluding one study, meta-regression did not show significant difference. CONCLUSIONS: Prophylactic, quadrivalent HPV vaccination can prevent GW in healthy women and men, therefore, it should be included in routine immunization programme.

Short-Course Antibiotic Treatment Is Not Inferior to a Long-Course One in Acute Cholangitis: A Systematic Review.

AIMS: Our aim was to summarize the available literature on the effect of short- versus long-course antibiotic therapy on acute cholangitis. METHODS: A systematic review was performed according to the PRISMA Statement. We searched three databases for papers discussing the length of ABT in acute cholangitis. Long and short therapy groups were defined based on the most recent guideline available at the time of publication of the articles. Primary outcomes were the rate of recurrent cholangitis and mortality; secondary outcomes included length of hospitalization and the duration of fever after ERCP. Data were extracted on these outcomes and on general characteristics. A narrative synthesis was then provided based on collected data. RESULTS: Out of 692 articles produced by our search, four met our inclusion and exclusion criteria. These contained 205 acute cholangitis patients, with 137 and 68 patients receiving short and long antibiotic therapy, respectively. No significant difference was observed in any of the studies on the outcomes of mortality and duration of fever after ERCP between the two groups. One out of four studies found the rate of recurrent cholangitis to be significantly lower in the short antibiotic therapy group (0.0% vs. 13.3%, p = 0.036). Length of hospitalization was only compared in the same retrospective article, where it was found to be significantly shorter in the short-term antibiotic therapy group (with a median of 14 vs. 17.5 days, p < 0.001). CONCLUSIONS: Our review suggests short-course antibiotic therapy is non-inferior to long-course treatment; however, several limitations underline the need for well-designed randomized trials.

The Efficacy of Saffron in the Treatment of Mild to Moderate Depression: A Meta-analysis.

Herbal products, especially Hypericum perforatum extracts, have been widely used as first-line treatments for mild to moderate depression. Recently, several randomized, controlled clinical trials have been conducted to evaluate the efficacy of another plant, saffron (Crocus sativus), in mild to moderate depression. We have carried out a literature review of currently available published randomized, controlled clinical trials to give an up-to-date evaluation of the efficacy of saffron in mild to moderate depression, compared to placebo or routinely used antidepressants. The meta-analysis is reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines using the PICO (patients, intervention, comparison, outcome) format and was conducted using the statistical programs Comprehensive Meta-analysis and RevMan. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science databases were searched for relevant studies. Only placebo or active controlled, randomized clinical studies involving patients suffering from mild to moderate depression and using pharmacological doses of saffron per os were included. Hedges' g was used to calculate effect sizes. Risk of bias was assessed using the Cochrane Collaboration tool, and heterogeneity was tested by both performing the Cochran's Q test and calculating Higgins' I2 indicator. Eleven randomized trials were included in the qualitative analysis, and nine were pooled for statistical analysis. According to the present meta-analysis, saffron has a significant effect on the severity of depression. Available data from randomized, controlled clinical trials support that saffron is significantly more effective than placebo (g = 0.891; 95% CI: 0.369 - 1.412, p = 0.001), and non-inferior to tested antidepressant drugs (g = - 0.246; 95% CI: - 0.495 - 0.004, p = 0.053).

Capsaicin and capsiate could be appropriate agents for treatment of obesity: A meta-analysis of human studies.

Consumption of capsaicin or its nonpungent analogues, capsinoids has been reported to affect energy expenditure and fat oxidation, although available data are still controversial. The aim of the present study was to conduct a meta-analysis regarding the effects of these substances on energy expenditure and respiratory quotient, with special emphasis on the role of body mass index (BMI) of the participants. Medical databases were systematically searched for papers. Of the 627 trials identified, 9 provided results suitable to be included in analysis. Data analysis showed that after ingestion of capsaicin or capsinoids the energy expenditure increased (245 kJ/day, 58.56 kcal/day, p = 0.030) and the respiratory quotient decreased (by 0.216; p = 0.031) indicating a rise in fat oxidation. Studies with mean BMI of the participants below 25 kg/m2 failed to report any effect of capsaicin or capsinoids on the energy expenditure (p = 0.718) or on the respiratory quotient (p = 0.444), but studies with mean BMI exceeding 25 kg/m2 demonstrated an increase in energy expenditure (292 kJ/day, 69.79 kcal/day, p = 0.023) and a marked decrease in respiratory quotient (-0.257, p = 0.036). Our data clearly suggest that capsaicin or capsiate could be a new therapeutic approach in obesity promoting a negative energy balance and increased fat oxidation.

Gender difference in the effects of interleukin-6 on grip strength - a systematic review and meta-analysis.

BACKGROUND: Aging sarcopenia characterized by low muscle mass with low muscle strength affects men and women differently. The contribution of interleukin-6 (IL-6) to sarcopenia has been suggested based on a negative correlation between plasma IL-6 and muscle function described by some studies. However, no consensus regarding clinically relevant cut-off criteria has been reached. Another question arises whether pooling male and female data is an accurate way to determine the predictive value of IL-6 in sarcopenia. The present meta-analysis was designed to assess: (1) whether plasma IL-6 in aged populations in fact correlates negatively to muscle strength; (2) whether such a correlation exists both in men and in women; and (3) whether plasma IL-6 shows a gender difference in old age. METHODS: We applied the preferred reporting items for systematic review and meta-analysis protocols (PRISMA). We searched PubMed and Embase for papers that reported data on individuals over 65 without inflammatory diseases. We extracted either separate male and female data on plasma IL-6 along with at least one muscle parameter or correlation coefficient between plasma IL-6 and these parameters. Random effect models calculated with DerSimonian and Laird weighting methods were applied to analyze correlation coefficients and gender difference in plasma IL-6. Egger's test was used to assess the small study effect. RESULTS: Twenty articles out of 468 records identified were suitable for analyses. Plasma IL-6 correlates negatively with grip strength in mixed populations and also separately in men [- 0.25 with 95% confidence interval (CI): - 0.48, - 0.02] and in women (- 0.14 with 95% CI: - 0.24, - 0.03). However, contrary to expectations, men with better muscle condition have higher plasma IL-6 than women of similar age with worse muscle condition (plasma IL-6 male-female difference: 0.25 pg/mL with 95% CI: 0.15, 0.35). CONCLUSION: This is the first study to demonstrate that a higher predictive IL-6 cut-off level should be determined for aging sarcopenia in men than in women.

Noninvasive ventilation improves the outcome in patients with pneumonia-associated respiratory failure: Systematic review and meta-analysis.

BACKGROUND: Noninvasive ventilation (NIV) is beneficial in exacerbations of chronic obstructive pulmonary disease (COPD), but its effectiveness in pneumonia-associated respiratory failure is still controversial. In the current meta-analysis, we aimed to investigate whether the use of NIV before intubation in pneumonia improves the mortality and intubation rates of respiratory failure as compared to no use of NIV in adults. METHODS: We searched three databases from inception to December 2019. We included studies, in which pneumonia patients were randomized initially into either NIV-treated or non-NIV-treated groups. Five full-text publications, including 121 patients, reported eligible data for statistical analysis. RESULTS: With NIV the overall hospital mortality rate seemed lower in patients with pneumonia-associated respiratory failure, but this was not significant [odds ratio (OR) = 0.39; 95% confidence interval (CI): 0.13-1.14; P = 0.085]. In the intensive care unit, the mortality was significantly lower when NIV was applied compared to no NIV treatment (OR = 0.22; 95% CI: 0.07-0.75; P = 0.015). NIV also decreased mortality compared to no NIV in patient groups, which did not exclude patients with COPD (OR = 0.25; 95% CI: 0.08-0.74; P = 0.013). The need for intubation was significantly reduced in NIV-treated patients (OR = 0.22; 95% CI: 0.09-0.53; P = 0.001), which effect was more prominent in pneumonia patient groups not excluding patients with pre-existing COPD (OR = 0.13; 95% CI: 0.03-0.46; P = 0.002). CONCLUSION: NIV markedly decreases the death rate in the intensive care unit and reduces the need for intubation in patients with pneumonia-associated respiratory failure. The beneficial effects of NIV seem more pronounced in populations that include patients with COPD. Our findings suggest that NIV should be considered in the therapeutic guidelines of pneumonia, given that future clinical trials confirm the results of our meta-analysis. AVAILABILITY OF DATA AND MATERIALS: All data and materials generated during the current study are available from the corresponding author on reasonable request.

Rats sniff out pulmonary tuberculosis from sputum: a diagnostic accuracy meta-analysis.

In Sub-Saharan Africa, African giant pouched rats (Cricetomys gambianus) are trained to identify TB patients by smelling sputum. We conducted a systematic review and meta-analysis of the data to see if this novel method is comparable to traditional laboratory screening and detection methods like Ziehl-Neelsen stain-based assays (ZN) and bacterial culture. The search and data processing strategy is registered at PROSPERO (CRD42019123629). Medline via PubMed, EMBASE, Web of Science, and Cochrane Library databases were systematically searched for the keywords "pouched rat" and "tuberculosis". Data from 53,181 samples obtained from 24,600 patients were extracted from seven studies. Using sample-wise detection, the sensitivity of the studies was 86.7% [95% CI 80.4-91.2%], while the specificity was 88.4% [95% CI 79.7-93.7%]. For patient-wise detection, the sensitivity was 81.3% [95% CI 64.0-91.4%], while the specificity was 73.4% [95% CI 62.8-81.9%]. Good and excellent classification was assessed by hierarchical summary receiver-operating characteristic analysis for patient-wise and sample-wise detections, respectively. Our study is the first systematic review and meta-analysis of the above relatively inexpensive and rapid screening method. The results indicate that African giant pouched rats can discriminate healthy controls from TB individuals by sniffing sputum with even a higher accuracy than a single ZN screening.

Computed Tomography Severity Index vs. Other Indices in the Prediction of Severity and Mortality in Acute Pancreatitis: A Predictive Accuracy Meta-analysis.

Background: The management of the moderate and severe forms of acute pancreatitis (AP) with necrosis and multiorgan failure remains a challenge. To predict the severity and mortality of AP multiple clinical, laboratory-, and imaging-based scoring systems are available. Aim: To investigate, if the computed tomography severity index (CTSI) can predict the outcomes of AP better than other scoring systems. Methods: A systematic search was performed in three databases: Pubmed, Embase, and the Cochrane Library. Eligible records provided data from consecutive AP cases and used CTSI or modified CTSI (mCTSI) alone or in combination with other prognostic scores [Ranson, bedside index of severity in acute pancreatitis (BISAP), Acute Physiology, and Chronic Health Examination II (APACHE II), C-reactive protein (CRP)] for the evaluation of severity or mortality of AP. Area under the curves (AUCs) with 95% confidence intervals (CIs) were calculated and aggregated with STATA 14 software using the metandi module. Results: Altogether, 30 studies were included in our meta-analysis, which contained the data of 5,988 AP cases. The pooled AUC for the prediction of mortality was 0.79 (CI 0.73-0.86) for CTSI; 0.87 (CI 0.83-0.90) for BISAP; 0.80 (CI 0.72-0.89) for mCTSI; 0.73 (CI 0.66-0.81) for CRP level; 0.87 (CI 0.81-0.92) for the Ranson score; and 0.91 (CI 0.88-0.93) for the APACHE II score. The APACHE II scoring system had significantly higher predictive value for mortality than CTSI and CRP (p = 0.001 and p < 0.001, respectively), while the predictive value of CTSI was not statistically different from that of BISAP, mCTSI, CRP, or Ranson criteria. The AUC for the prediction of severity of AP were 0.80 (CI 0.76-0.85) for CTSI; 0.79, (CI 0.72-0.86) for BISAP; 0.83 (CI 0.75-0.91) for mCTSI; 0.73 (CI 0.64-0.83) for CRP level; 0.81 (CI 0.75-0.87) for Ranson score and 0.80 (CI 0.77-0.83) for APACHE II score. Regarding severity, all tools performed equally. Conclusion: Though APACHE II is the most accurate predictor of mortality, CTSI is a good predictor of both mortality and AP severity. When the CT scan has been performed, CTSI is an easily calculable and informative tool, which should be used more often in routine clinical practice.

Lactose intolerance but not lactose maldigestion is more frequent in patients with irritable bowel syndrome than in healthy controls: A meta-analysis.

BACKGROUND AND PURPOSE: Irritable bowel syndrome (IBS) affects 10%-20% of the adult population and is characterized by abdominal symptoms without relevant organic disease. There are numerous clinical trials available investigating the relationship between IBS, lactose maldigestion (LM), and lactose intolerance (LI), but there have been no meta-analyses on this topic yet. We aimed to assess the prevalence of LM, objective and subjective (self-reported) LI in IBS patients compared to healthy controls (HC) without IBS. METHODS: A systematic literature search was conducted up to 24 April 2018 in PubMed, Embase, and Cochrane Library. Adult IBS patients had to be diagnosed according to the Rome criteria or other well-defined criteria system. We enrolled controlled studies including healthy adult participants without IBS, as control group. Odds ratios with 95% confidence intervals were calculated. KEY RESULTS: Altogether 14 articles were suitable for statistical analyses. IBS patients reported themselves significantly more frequently lactose intolerant than HCs (odds ratio [OR] = 3.499; 95% confidence interval [CI] = 1.622-7.551). Generally, there was no significant difference in the prevalence of LM based on ingested lactose dose (OR = 1.122; 95% CI = 0.929-1.356) and test type (OR = 1.156; 95% CI = 0.985-1.356). However, significantly more IBS patients had objective LI (OR = 2.521; 95% CI = 1.280-4.965). CONCLUSIONS AND INFERENCES: Lactose intolerance, but not LM is more frequent among patients with IBS compared to HCs. According to our results, IBS among other functional bowel disorders is a possible contributing factor of LI in people with LM.

The combination of hawthorn extract and camphor significantly increases blood pressure: A meta-analysis and systematic review.

BACKGROUND: A fixed combination of hawthorn and camphor (Korodin Herz-Kreislauf-Tropfen®) has been used in the therapy of hypotension for decades. Although its efficacy was evaluated in clinical trials, these studies have not been critically assessed in meta-analyses. PURPOSE: To systematically evaluate the efficacy of a fix combination of camphor and hawthorn extract (Korodin®) on blood pressure and cognition compared to placebo, in a meta-analysis based on randomized controlled trials (RCTs). STUDY DESIGN: The meta-analysis was carried out following the PRISMA guidelines, using the PICO format, and it was registered in the PROSPERO register. METHODS: The Cochrane Central Register of Controlled Trials, PubMed, Embase, and Web of Science databases were searched for relevant studies. Placebo-controlled clinical studies involving adult patients receiving a fix combination of hawthorn extract and camphor were included. No language or publication year restrictions were applied. RESULTS: Four randomized trials including a total of 221 patients were pooled for statistical analysis. According to the present meta-analysis, the fixed combination of hawthorn and camphor significantly increases systolic and diastolic blood pressure compared to placebo (p-values: 0.017 and 0.049, respectively) and had a beneficial, but not statistically significant effect on the cognitive performance in the connect-the-numbers test (p-value: 0.071). CONCLUSION: Korodin® is an effective and presumably safe complementary therapy for the treatment of hypotension. Its blood pressure increasing effect is confirmed; however, the evidence supporting its use is very limited. The optimum dose and duration of treatment is still unclear. The comprehensive evaluation of efficacy and safety is required in further, high-quality clinical studies, involving larger patient populations and comparable endpoints.

Activity of the Hypothalamic Melanocortin System Decreases in Middle-Aged and Increases in Old Rats.

Appearance of middle-aged obesity and aging anorexia both in humans and rodents suggests a role for regulatory alterations. Hypothalamic melanocortin agonist, α-melanocyte-stimulating hormone (α-MSH) produced in the arcuate nucleus (ARC), reduces body weight via inducing hypermetabolism and anorexia mainly through melanocortin 4 receptors (MC4Rs) in the paraventricular nucleus (PVN). Orexigenic ARC-derived agouti-related protein (AgRP) is an inverse agonist on MC4R in the PVN. Previously, we demonstrated that characteristic age-related shifts in the catabolic effects of α-MSH may contribute both to middle-aged obesity and aging anorexia. Responsiveness to α-MSH decreases in middle-aged rats compared with young adults, whereas in old age it rises again significantly. We hypothesized corresponding age-related dynamics of endogenous melanocortins. Therefore, we quantified mRNA gene expression and peptide or protein level of α-MSH, AgRP, and MC4R in the ARC and PVN of male Wistar rats of five age groups (from young to old). Immunofluorescence and quantitative reverse transcriptase polymerase chain reaction were applied. α-MSH and MC4R immunoreactivities in the ARC and PVN declined in middle-aged and increased together with their expressions in aging rats. AgRP gene expression but not its immunoreactivity increased in aging rats. Our results demonstrate that age-dependent changes of endogenous melanocortins contribute to middle-aged obesity and aging anorexia.

Body fat of rats of different age groups and nutritional states: assessment by micro-CT and skinfold thickness.

Obesity presents a growing public health problem. Therefore the analysis of body composition is important in clinical practice as well as in animal research models of obesity; hence precise methods for the assessment of body fat would be essential. We aimed to evaluate in vivo abdominal microcomputed tomography scan restricted to the L1-L3 region [micro-CT(L1-L3)], a skinfold thickness-based method (STM), and postmortem body composition analysis (PMA) with regard to whole body micro-CT scan in rats. Male Wistar rats of different age groups (from 3 to 24 mo) and nutritional states (normally fed, high-fat diet-induced obese, and calorie-restricted) were used. The fat percentage was determined with micro-CT(L1-L3) and whole body scan in anesthetized rats. Their skinfold thickness was measured in five locations with a Lange caliper. Wet weights of epididymal and retroperitoneal fat pads were determined via PMA. With regard to fat mass, the strongest correlation was observed between abdominal and whole body micro-CT. The other methods showed weaker associations with whole body micro-CT and with each other. Micro-CT(L1-L3) and PMA showed similar age-associated increase in fat mass between 3 and 18 mo. Micro-CT(L1-L3), STM, and PMA were efficient to detect differences in fat mass values in groups of different nutritional states. Micro-CT(L1-L3) appears to be a useful method for body fat assessment in rats with reduced scanning time. In rats, STM may also be a useful, low priced, noninvasive, and simple in vivo technique to assess obesity. NEW & NOTEWORTHY Body fat of rats assessed by in vivo abdominal microcomputed tomography of the L1-L3 region strongly correlates with values determined by whole body scan. Therefore, it is a useful method for fat assessment with reduced scanning time. Skinfold thickness measurement is an in vivo technique to assess progression of obesity in rats.

Perceived stress correlates with visceral obesity and lipid parameters of the metabolic syndrome: A systematic review and meta-analysis.

BACKGROUND: Perceived stress has been proposed as a risk factor of metabolic syndrome. However, correlations between perceived stress and parameters of the metabolic syndrome have not been properly analyzed despite extensive research data on the topic. Our current meta-analysis aimed to examine the mutual association between perceived stress of patients and parameters of metabolic syndrome. METHODS: This systematic review has been registered on the PROSPERO database (registration number CRD42017055293). Eligible studies divided participants based on their stress level or on the presence of metabolic syndrome. They reported at least one parameter of the metabolic syndrome or the stress level of the participants measured with some stress scale. Data from 17 articles met the eligibility criteria and were included. Random effects model with the DerSimonian and Laird weighting methods was applied. I-squared indicator and Q test were performed to assess heterogeneity. RESULTS: Although the majority of individual studies failed to demonstrate correlations between stress and their analyzed parameters of metabolic syndrome, our meta-analysis showed a significant association between stress and BMI [average effect size (ES) with 95% confidence interval (95%CI), ES = 0.65, 95%CI 0.16, 1.14), waist circumference (ES = 1.84 cm, 95%CI 0.79, 2.89) and serum triglyceride level (ES = 7.52 mg/dl, 95%CI 0.07, 14.96). Additional analysis confirmed effects of stress on serum HDL (ES = - 1.699 mg/dl, 95%CI -2.966, -0.432) and diastolic blood pressure (ES = 1.04 mmHg, 95%CI 0.18, 1.89). No correlations were found for fasting glucose or systolic blood pressure. No association between metabolic syndrome and stress level of patients was detected either. CONCLUSION: The potentially key role of visceral obesity in the association between perceived stress and dyslipidemia or diastolic blood pressure are discussed together with potential moderators (e.g. gender-differences, variations in stress assessment and metabolic syndrome criteria) that may explain the inconsistent, contradictory results of the individual studies.

Therapeutic Whole-Body Hypothermia Reduces Death in Severe Traumatic Brain Injury if the Cooling Index Is Sufficiently High: Meta-Analyses of the Effect of Single Cooling Parameters and Their Integrated Measure.

Therapeutic hypothermia was investigated repeatedly as a tool to improve the outcome of severe traumatic brain injury (TBI), but previous clinical trials and meta-analyses found contradictory results. We aimed to determine the effectiveness of therapeutic whole-body hypothermia on the deaths of adult patients with severe TBI by using a novel approach of meta-analysis. We searched the PubMed, EMBASE, and Cochrane Library databases from inception to February 2017. The identified human studies were evaluated regarding statistical, clinical, and methodological designs to ensure interstudy homogeneity. We extracted data on TBI severity, body temperature, death, and cooling parameters; then we calculated the cooling index, an integrated measure of therapeutic hypothermia. Forest plot of all identified studies showed no difference in the outcome of TBI between cooled and not cooled patients, but interstudy heterogeneity was high. On the contrary, by meta-analysis of randomized clinical trials that were homogenous with regard to statistical, clinical designs, and precisely reported the cooling protocol, we showed decreased odds ratio for death in therapeutic hypothermia compared with no cooling. As independent factors, milder and longer cooling, and rewarming at <0.25°C/h were associated with better outcome. Therapeutic hypothermia was beneficial only if the cooling index (measure of combination of cooling parameters) was sufficiently high. We conclude that high methodological and statistical interstudy heterogeneity could underlie the contradictory results obtained in previous studies. By analyzing methodologically homogenous studies, we show that cooling improves the outcome of severe TBI, and this beneficial effect depends on certain cooling parameters and on their integrated measure, the cooling index.

Age-related changes in central effects of corticotropin-releasing factor (CRF) suggest a role for this mediator in aging anorexia and cachexia.

Hypothalamic corticotropin-releasing factor (CRF) lays downstream to catabolic melanocortins and at least partly mediates their catabolic effects. Age-related changes in the melanocortin system (weak responsiveness in middle-aged and a strong one in old rats) have been shown to contribute to middle-aged obesity and later to aging anorexia and cachexia of old age groups. We hypothesized that catabolic (anorexigenic and hypermetabolic) CRF effects vary with aging similarly to those of melanocortins. Thus, we aimed to test whether age-related variations of CRF effects may also contribute to middle-aged obesity and aging anorexia leading to weight loss of old age groups. Food intake, body weight, core temperature, heart rate, and activity were recorded in male Wistar rats of young, middle-aged, aging, and old age groups (from 3 to 24 months) during a 7-day intracerebroventricular CRF infusion (0.2 µg/µl/h) in a biotelemetric system. In addition, CRF gene expression was also assessed by quantitative RT-PCR in the paraventricular nucleus (PVN) of intact animals of the same age groups. The infusion suppressed body weight in the young, aging, and old rats, but not in middle-aged animals. Weak anorexigenic and hypermetabolic effects were detected in the young, whereas strong anorexia (without hypermetabolism) developed in the oldest age groups in which post mortem analysis showed also a reduction of retroperitoneal fat mass. CRF gene expression in the PVN increased with aging. Our results support the potential contribution of age-related changes in CRF effects to aging anorexia and cachexia. The role of the peptide in middle-aged obesity cannot be confirmed.

Acute central effects of alarin on the regulation on energy homeostasis.

Hypothalamic neuropeptides influence the main components of energy balance: metabolic rate, food intake, body weight as well as body temperature, by exerting either an overall anabolic or catabolic effect. The contribution of alarin, the most recently discovered member of the galanin peptide family to the regulation of energy metabolism has been suggested. Our aim was to analyze the complex thermoregulatory and food intake-related effects of alarin in rats. Adult male Wistar rats received different doses of alarin (0.3; 1; 3 and 15µg corresponding approximately to 0.1, 0.33, 1, and 5 nmol, respectively) intracerebroventricularly. Regarding thermoregulatory analysis, oxygen consumption (indicating metabolic rate), core temperature and heat loss (assessed by tail skin temperature) were recorded in an Oxymax indirect calorimeter system complemented with thermocouples and Benchtop thermometer. In order to investigate potential prostaglandin-mediated mechanisms of the hyperthermic effect of alarin, effects of intraperitoneally applied non-selective (indomethacin, 2mg/kg) or selective cyclooxygenase inhibitor (COX-2 inhibitor meloxicam, 1; 2mg/kg) were tested. Effects of alarin on daytime and nighttime spontaneous food intake, as well as, 24-h fasting-induced re-feeding were recorded in an automated FeedScale system. Alarin increased oxygen consumption with simultaneous suppression of heat loss leading to a slow coordinated rise in core temperature. Both applied COX-inhibitors suppressed this action. Alarin failed to induce daytime food intake, but suppressed spontaneous nighttime and also fasting-induced re-feeding food intake. Alarin appears to elicit a slow anorexigenic and prostaglandin-mediated, fever-like hyperthermic response in rats. Such a combination would characterize a catabolic mediator. The potential involvement of alarin in sickness behavior may be assumed.

In middle-aged and old obese patients, training intervention reduces leptin level: A meta-analysis.

BACKGROUND: Leptin is one of the major adipokines in obesity that indicates the severity of fat accumulation. It is also an important etiological factor of consequent cardiometabolic and autoimmune disorders. Aging has been demonstrated to aggravate obesity and to induce leptin resistance and hyperleptinemia. Hyperleptinemia, on the other hand, may promote the development of age-related abnormalities. While major weight loss has been demonstrated to ameliorate hyperleptinemia, obese people show a poor tendency to achieve lasting success in this field. The question arises whether training intervention per se is able to reduce the level of this adipokine. OBJECTIVES: We aimed to review the literature on the effects of training intervention on peripheral leptin level in obesity during aging, in order to evaluate the independent efficacy of this method. In the studies that were included in our analysis, changes of adiponectin levels (when present) were also evaluated. DATA SOURCES: 3481 records were identified through searching of PubMed, Embase and Cochrane Library Database. Altogether 19 articles were suitable for analyses. STUDY ELIGIBILITY CRITERIA: Empirical research papers were eligible provided that they reported data of middle-aged or older (above 45 years of age) overweight or obese (body mass index above 25) individuals and included physical training intervention or at least fitness status of groups together with corresponding blood leptin values. STATISTICAL METHODS: We used random effect models in each of the meta-analyses calculating with the DerSimonian and Laird weighting methods. I-squared indicator and Q test were performed to assess heterogeneity. To assess publication bias Egger's test was applied. In case of significant publication bias, the Duval and Tweedie's trim and fill algorithm was used. RESULTS: Training intervention leads to a decrease in leptin level of middle-aged or older, overweight or obese male and female groups, even without major weight loss, indicated by unchanged serum adiponectin levels. Resistance training appears to be more efficient in reducing blood leptin level than aerobic training alone. CONCLUSIONS: Physical training, especially resistance training successfully reduces hyperleptinemia even without diet or major weight loss.

Fever Is Associated with Reduced, Hypothermia with Increased Mortality in Septic Patients: A Meta-Analysis of Clinical Trials.

BACKGROUND: Sepsis is usually accompanied by changes of body temperature (Tb), but whether fever and hypothermia predict mortality equally or differently is not fully clarified. We aimed to find an association between Tb and mortality in septic patients with meta-analysis of clinical trials. METHODS: We searched the PubMed, EMBASE, and Cochrane Controlled Trials Registry databases (from inception to February 2016). Human studies reporting Tb and mortality of patients with sepsis were included in the analyses. Average Tb with SEM and mortality rate of septic patient groups were extracted by two authors independently. RESULTS: Forty-two studies reported Tb and mortality ratios in septic patients (n = 10,834). Pearson correlation analysis revealed weak negative linear correlation (R2 = 0.2794) between Tb and mortality. With forest plot analysis, we found a 22.2% (CI, 19.2-25.5) mortality rate in septic patients with fever (Tb > 38.0°C), which was higher, 31.2% (CI, 25.7-37.3), in normothermic patients, and it was the highest, 47.3% (CI, 38.9-55.7), in hypothermic patients (Tb < 36.0°C). Meta-regression analysis showed strong negative linear correlation between Tb and mortality rate (regression coefficient: -0.4318; P < 0.001). Mean Tb of the patients was higher in the lowest mortality quartile than in the highest: 38.1°C (CI, 37.9-38.4) vs 37.1°C (CI, 36.7-37.4). CONCLUSIONS: Deep Tb shows negative correlation with the clinical outcome in sepsis. Fever predicts lower, while hypothermia higher mortality rates compared with normal Tb. Septic patients with the lowest (< 25%) chance of mortality have higher Tb than those with the highest chance (> 75%).

Regulatory Alterations of Energy Homeostasis in Spontaneously Hypertensive Rats (SHR).

Spontaneously hypertensive rats (SHR) have high sympathetic tone and progressive hypertension. Chronic calorie-restriction prevents hypertension. Their food intake (FI) and body weight are lower than in normotensive (NT) controls, even on a high-fat diet, suggesting a dysregulation of energy homeostasis. We assumed enhanced activity of hypothalamic anorexigenic melanocortins and diminished tone of orexigenic neuropeptide Y (NPY) in the background. FI of male SHR and NT Wistar rats was recorded in a FeedScale system upon intracerebroventricular injection of NPY, melanocortin ligands alpha-melanocyte-stimulating hormone (alpha-MSH), and agouti-related peptide (AgRP) or during a 7-day intracerebroventricular infusion of melanocortin antagonist HS024. Alpha-MSH, NPY, and AgRP immunoreactivities were semi-quantified in the arcuate (ARC) and paraventricular (PVN) nuclei of the hypothalamus in NT vs. SHR. Proopiomelanocortin gene expression was also assessed by quantitative RT-PCR in the ARC. Melanocortin-induced anorexia was stronger, FI induced by NPY or HS024 was smaller and delayed in SHR. Cellular alpha-MSH-specific signal density was higher in the ARC of SHR as evaluated by immunofluerescence, which was supported by PCR data. In the PVN, no differences in alpha-MSH-, NPY-, or AgRP-immunosignal were observed. Our results suggest that a higher melanocortin production/responsiveness and lower NPY responsiveness may contribute to the body weight dysregulation of SHR.