Ammonium chloride-induced hypothermia is attenuated by transient receptor potential channel vanilloid-1, but augmented by ankyrin-1 in rodents.

AIMS: Systemic administration of ammonium chloride (NH4Cl), an acidifying agent used in human patients and experimental conditions, causes hypothermia in mice, however, the mechanisms of the thermoregulatory response to NH4Cl and whether it develops in other species remained unknown. MAIN METHODS: We studied body temperature (Tb) changes in rats and mice induced by intraperitoneal administration of NH4Cl after blockade of transient receptor potential vanilloid-1 (TRPV1) or ankyrin-1 (TRPA1) channels. KEY FINDINGS: In rats, NH4Cl decreased Tb by 0.4-0.8°C (p < 0.05). The NH4Cl-induced hypothermia also developed in Trpv1 knockout (Trpv1-/-) and wild-type (Trpv1+/+) mice, however, the Tb drop was exaggerated in Trpv1-/- mice compared to Trpv1+/+ controls with maximal decreases of 4.0 vs. 2.1°C, respectively (p < 0.05). Pharmacological blockade of TRPV1 channels with AMG 517 augmented the hypothermic response to NH4Cl in genetically unmodified mice and rats (p < 0.05 for both). In contrast, when NH4Cl was infused to mice genetically lacking the TRPA1 channel, the hypothermic response was significantly attenuated compared to wild-type controls with maximal mean Tb difference of 1.0°C between the genotypes (p = 0.008). Pretreatment of rats with a TRPA1 antagonist (A967079) also attenuated the NH4Cl-induced Tb drop with a maximal difference of 0.7°C between the pretreatment groups (p = 0.003). SIGNIFICANCE: TRPV1 channels limit, whereas TRPA1 channels exaggerate the development of NH4Cl-induced hypothermia in rats and mice, but other mechanisms are also involved. Our results warrant for regular Tb control and careful consideration of NH4Cl treatment in patients with TRPA1 and TRPV1 channel dysfunctions.

Efficacy of Topical Essential Oils in Musculoskeletal Disorders: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Essential oils (EOs) are widely used topically in musculoskeletal disorders (MSDs); however, their clinical efficacy is controversial. Our aim was to find evidence that topical EOs are beneficial as an add-on treatment in MSDs. We performed a systematic review and meta-analysis to summarize the evidence on the available data of randomized controlled trials (RCTs). The protocol of this work was registered on PROSPERO. We used Web of Science, EMBASE, PubMed, Central Cochrane Library and Scopus electronic databases for systematic search. Eight RCTs were included in the quantitative analysis. In conclusion, EO therapy had a favorable effect on pain intensity (primary outcome) compared to placebo. The greatest pain-relieving effect of EO therapy was calculated immediately after the intervention (MD of pain intensity = -0.87; p = 0.014). EO therapy had a slightly better analgesic effect than placebo one week after the intervention (MD of pain intensity = -0.58; p = 0.077) and at the four-week follow-up as well (MD of pain intensity = -0.52; p = 0.049). EO therapy had a beneficial effect on stiffness (a secondary outcome) compared to the no intervention group (MD = -0.77; p = 0.061). This systematic review and meta-analysis showed that topical EOs are beneficial as an add-on treatment in reducing pain and stiffness in the investigated MSDs.

Precision Medicine in Pancreatitis: The Future of Acute Pancreatitis Care.

Acute pancreatitis (AP) continues to present a substantial burden to patients and healthcare personnel. Despite its occasionally severe progression and high mortality rate, there is no specific therapy that could be routinely applied in patients with AP. Here, we review treatment possibilities in AP, describe how the treatment approaches have changed in pancreatic cancer as an analogy, and point out potential causes for the failure of clinical trials on AP. We highlight that instead of attempting to discover generalized treatment options that could be used in any AP patient, it is time for a paradigm shift in the treatment of AP, which would help to focus more on individual patients or specific patient subpopulations when designing clinical trials and therapeutic approaches (similarly as in pancreatic cancer). Since the recruitment of specific patient subpopulations with AP could take excessive time if clinical centers work separately, the development of precision medicine in AP would require to establish an expert committee, eg, Pancreatitis Precision Medicine Interest Group, which could organize and coordinate the activities of the joined centers. With the joined forces of expert clinicians and leading centers, a new era could start in the treatment of AP, in which personalized treatment options could be discovered and introduced to efficiently reduce the burden of the disease on patients and healthcare workers.

The neural pathway of the hyperthermic response to antagonists of the transient receptor potential vanilloid-1 channel.

We identified the neural pathway of the hyperthermic response to TRPV1 antagonists. We showed that hyperthermia induced by i.v. AMG0347, AMG 517, or AMG8163 did not occur in rats with abdominal sensory nerves desensitized by pretreatment with a low i.p. dose of resiniferatoxin (RTX, TRPV1 agonist). However, neither bilateral vagotomy nor bilateral transection of the greater splanchnic nerve attenuated AMG0347-induced hyperthermia. Yet, this hyperthermia was attenuated by bilateral high cervical transection of the spinal dorsolateral funiculus (DLF). To explain the extra-splanchnic, spinal mediation of TRPV1 antagonist-induced hyperthermia, we proposed that abdominal signals that drive this hyperthermia originate in skeletal muscles - not viscera. If so, in order to prevent TRPV1 antagonist-induced hyperthermia, the desensitization caused by i.p. RTX should spread into the abdominal-wall muscles. Indeed, we found that the local hypoperfusion response to capsaicin (TRPV1 agonist) in the abdominal-wall muscles was absent in i.p. RTX-desensitized rats. We then showed that the most upstream (lateral parabrachial, LPB) and the most downstream (rostral raphe pallidus) nuclei of the intrabrain pathway that controls autonomic cold defenses are also required for the hyperthermic response to i.v. AMG0347. Injection of muscimol (inhibitor of neuronal activity) into the LPB or injection of glycine (inhibitory neurotransmitter) into the raphe blocked the hyperthermic response to i.v. AMG0347, whereas i.v. AMG0347 increased the number of c-Fos cells in the raphe. We conclude that the neural pathway of TRPV1 antagonist-induced hyperthermia involves TRPV1-expressing sensory nerves in trunk muscles, the DLF, and the same LPB-raphe pathway that controls autonomic cold defenses.

Mid-Term Follow-Up Study of Children Undergoing Autologous Skin Transplantation for Burns.

Deep partial and full-thickness burns require surgical treatment with autologous skin grafts after necrectomy, which is the generally accepted way to achieve permanent wound coverage. This study sought to examine the grafted and donor areas of children who underwent autologous skin transplantation, using two assessment scales to determine the severity of the scarring and the cosmetic outcome during long-term follow-up. At the Surgical Unit of the Department of Paediatrics of the University of Pécs, between 1 January 2015 and 31 December 2019, children who had been admitted consecutively and received autologous skin transplantation were analyzed. Twenty patients met the inclusion criteria in this retrospective cohort study. The authors assessed the results using the Patient and Observer Scar Assessment Scale (POSAS) and the Vancouver Scar Scale (VSS). There was a significant difference in how parents and examiners perceived the children's scars. In the evaluation of the observer scale, the most critical variables for the area of skin grafted were relief and thickness. Besides color, relief was the worst clinical characteristic on the patient scale. However, when medical professionals evaluated the donor site, significantly better results were obtained compared to the transplanted area (average observer scale score: 1.4 and 2.35, p = 0.001; VSS: 0.85 vs. 2.60, p < 0.001), yet it was similar to the graft site in the parents' opinion (Patient Scale: 2.95 and 4.45, p = 0.181).

Distinct patterns of serum and urine macrophage migration inhibitory factor kinetics predict death in sepsis: a prospective, observational clinical study.

Macrophage migration inhibitory factor (MIF) has been considered as a biomarker in sepsis, however the predictive value of the pattern of its kinetics in the serum and in the urine has remained unclarified. It is also unclear whether the kinetics of MIF are different between males and females. We conducted a single-center prospective, observational study with repeated measurements of MIF in serum and urine on days 0, 2, and 4 from admission to the intensive care unit (ICU) in 50 adult septic patients. We found that in patients who died within 90 days, there was an increase in serum MIF level from day 0 to 4, whereas in the survivors there was rather a decrease (p = 0.018). The kinetics were sex-dependent as the same difference in the pattern was present in males (p = 0.014), but not in females (p = 0.418). We also found that urine MIF was markedly lower in patients who died than in survivors of sepsis (p < 0.050). Urine MIF levels did not show temporal changes: there was no meaningful difference between day 0 and 4. These results suggest that kinetics of serum MIF during the initial days from ICU admission can predict death, especially in male patients. Additionally, lower urine MIF levels can also indicate death without showing meaningful temporal kinetics.

Synthesis and evaluation of a new class of MIF-inhibitors in activated macrophage cells and in experimental septic shock in mice.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with enzymatic activities. Anti-inflammatory effects of MIF enzyme inhibitors indicate a link between its cytokine- and catalytic activities. Herein the synthesis, docking, and bioactivity of substituted benzylidene-1-indanone and -1-tetralone derivatives as MIF-tautomerase inhibitors is reported. Many of these substituted benzylidene-1-tetralones and -indan-1-ones were potent MIF-tautomerase inhibitors (IC50 < 10 µmol/L), and the most potent inhibitors were the 1-indanone derivatives 16 and 20. Some of these compounds acted as selective enolase or ketonase inhibitors. In addition, compounds 16, 20, 26, 37 and 61 efficiently inhibited NO, TNFα and IL-6 production in lipopolysaccharide-induced macrophages. Compound 20, 37 and 61 also inhibited ROS generation, and compound 26 and 37 abolished activation of NF-κB. Compound 37 significantly augmented hypothermia induced by high dose of lipopolysaccharide in mice. The possible mechanisms of action were explored using molecular modelling and docking, as well as molecular dynamics simulations.

Increased risk of adverse events in patients with low-on clopidogrel platelet reactivity after percutaneous coronary intervention: A systematic review and meta-analysis.

BACKGROUND: Clinical evidence has been controversial regarding the influence of low platelet reactivity (LPR), ischemic and bleeding outcomes among patients receiving coronary stent implantation. Hence, the present study performed a meta-analysis to systematically evaluate the significance of LPR on adverse cardiovascular events. METHODS: MEDLINE, EMBASE and CENTRAL databases were searched up to November 2020 for relevant studies including patients with acute coronary syndrome undergoing percutaneous coronary intervention. LPR was the exposed arm while the non-LPR group represented the control. The primary outcome of interest was bleeding risk including major and minor bleeding events. Secondary outcomes included all-cause mortality, repeated revascularization, nonfatal myocardial infarction, and stent thrombosis. Study-level outcomes were evaluated in random-effect models. RESULTS: A total of 20 studies with 19,064 patients were included. Pooled analysis showed that LPR was associated with an increased bleeding risk (relative risk [RR] 2.80, 95% confidence interval [CI] 1.95-4.02, p < 0.01). Patients with LPR had a lower risk of non-fatal myocardial infarction (RR 0.59, 95% CI 0.38-0.91, p < 0.05) and of serious vascular events (RR 0.50, 95% CI 0.30-0.84, p < 0.01). CONCLUSIONS: Low platelet reactivity is associated with an increased bleeding risk of patients who underwent coronary stent implantation. The results suggest possible benefits of this marker in risk stratification, with potential improvement in risk prediction. There are potential advantages using combinations with other factors in prediction models, however, they require further study. PROSPERO registration number: CRD42019136393).

Effectiveness of four topical treatment methods in a rat model of superficial partial-thickness burn injury: the advantages of combining zinc-hyaluronan gel with silver foam dressing.

BACKGROUND: There are several options available for conservative treatment of partial-thickness burns, however, reliable, affordable, and easily obtainable animal testing models are hard to find for the comparison of the different treatment methods. We aimed at developing a preclinical testing model and at comparing four treatment methods for superficial partial-thickness burns. METHODS: Burn injury was induced in 90 adult male Wistar rats by placing the 130°C hot tip of a commercially obtainable soldering device for 30 s on the clipped skin of the interscapular region at a steady pressure. Skin histology was studied on days 5, 10, and 22 after the induction of the burn injury, on which days, respectively, the ratio of the not epithelialized wound (%), the extent of re-epithelialization (score), and the scar thickness (µm) were assessed. We compared 4 groups: silver-sulfadiazine cream, zinc-hyaluronan gel, silver foam dressing, and the combination of zinc-hyaluronan gel with a silver foam dressing. RESULTS: On day 5, the induction of superficial partial-thickness burn injury was confirmed histologically in the rats. The zinc-hyaluronan gel and the combination treatment resulted in a markedly smaller ratio of the non-epithelialized area (29 ± 10% and 28 ± 13%, respectively) than silver-sulfadiazine cream (69 ± 4%; p < 0.01). On day 10, the extent of re-epithelialization was the lowest (∼0.2) in the silver-sulfadiazine cream group, while the other 3 treatments performed significantly better. The combination treatment lead to the maximal score of 2 in all rats, which was higher than in the other 3 treatment groups. On day 22, the scar thickness was the smallest in the combination treatment group (560 ± 42 µm), which was significantly less than in the silver-sulfadiazine cream group (712 ± 38 µm; p < 0.05). CONCLUSIONS: We designed and histologically confirmed a reproducible method for induction of superficial partial-thickness burns in rats for preclinical testing. In our model, the combination of zinc-hyaluronan gel with silver foam dressing was more effective than either of its components alone or than silver-sulfadiazine cream.

Management of Pediatric Facial Burns with Zinc-Hyaluronan Gel.

Zinc-hyaluronan-containing burn dressings have been associated with enhanced reepithelialization and low infection rates, although their effectiveness has not yet been investigated in pediatric facial thermal injuries. This single-arm, retrospective cohort study assessed the characteristics of 23 children (≤17-year-old) with facial superficial partial-thickness burns and the wound closure capabilities of the applied zinc-hyaluronan gel. Patients were admitted consecutively to the Pediatric Surgery Division in Pécs, Hungary, between 1 January 2016 and 15 October 2021. The mean age of the children was 6.2 years; 30.4% of them were younger than 1 year. An average of 3% total body surface was injured in the facial region and 47.8% of the patients had other areas damaged as well, most frequently the left upper limb (30.4%). The mean time until complete reepithelialization was 7.9 days and the children spent 2 days in the hospital. Wound cultures revealed normal bacterial growth in all cases and follow-up examinations found no hypertrophic scarring. In conclusion, pediatric facial superficial partial-thickness burns are prevalent during infancy and coincide with left upper limb injuries. Rapid wound closure and low complication rates are accountable for the moderate amount of hospitalization. These benefits, along with the gel's ease of applicability and spontaneous separation, are linked to child-friendly burn care.

Paediatric Partial-Thickness Burn Therapy: A Meta-Analysis and Systematic Review of Randomised Controlled Trials.

BACKGROUND: Paediatric second-degree burn injuries are a significant source of medical challenges to the population that may cause severe, lifelong complications. Currently, there are dozens of therapeutic modalities and we aimed to summarise their reported outcomes and determine their effectiveness, compared to the widely used silver sulphadiazine (SSD). METHODS: We conducted the meta-analysis and systematic review of randomised controlled trials (RCTs), which investigated the performance of dressings in acute paediatric partial-thickness burns. The evaluated endpoints were time until wound closure, grafting and infection rate, number of dressing changes and length of hospitalisation. RESULTS: Twenty-nine RCTs were included in the qualitative and 25 in the quantitative synthesis, but only three trials compared SSD directly to the same intervention (Biobrane). Data analysis showed a tendency for faster healing times and a reduced complication rate linked to biosynthetic, silver foam and amnion membrane dressings. A substantial difference was found between the number of dressing changes associated with less pain, narcosis and treatment duration. CONCLUSIONS: Considerable between-study heterogeneity was caused by the unequal depth subcategory ratio and surface area of the injuries; therefore, no significant difference was found in the main outcomes. Further research is necessary to establish the most effective treatment for these burns.

Case reports of pediatric electrical finger burn injuries' management and late- onset complications / Gyermekkori, áramégés okozta kézujjsérülések ellátásáról és késoi szövodményeirol

Pediatric electrical injuries are rare; they only constitute 2-10% of all burn causes. Determination of their actual severity may be challenging due to their small entry and exit wounds. Deep necrosis develops during electrical burns in most cases. These injuries can damage the skin, soft and bone tissues, and in children, the growth plate, which may cause secondary deformities. The objective of these case reports was the presentation of paediatric electrical finger injuries' management and late-onset complications. A 15-year-old boy touched an electric wire while changing a lightbulb, which caused a burn injury on his right index finger. During the physical examination, a 25 x 14 mm, third-degree burn was identified volarly, above the distal interphalangeal joint as an entry wound, and an 8 x 7 mm exit site occurred dorsally at the nailbed's lateral edge. Necrectomy and cross finger flap surgery were performed. The cross flap was separated three weeks after the primary reconstruction. Throughout the follow-up examinations, the ulnar deviation of the distal digit was observed. X-ray confirmed the bone atrophy of the distal phalanx base. A 2-year old girl inserted a nail into the power outlet, causing third-degree burns on her thumb around the interphalangeal joint and hypothenar region. After necrectomy, the thumb's skin defect was reconstructed with a rotated flap, while the donor site received full-thickness skin graft transplantation. The follow-up of the child is still ongoing. Long term follow-up of these patients is necessary to identify and treat late-onset complications.

Efficacy of Treatments in Nonarteritic Ischemic Optic Neuropathy: A Systematic Review and Meta-Analysis.

BACKGROUND: Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) is the second most common cause of optic nerve-related permanent visual loss in adults. AIM: We aimed to analyze the efficacy of the noninvasive and minimally invasive therapeutic options of NAION. METHODS: We performed a systematic literature search in MEDLINE, EMBASE, and CENTRAL from inception to 10 June 2019 to identify the studies that report on the effect of different therapies on visual acuity (VA) and visual field (VF). Weighted mean difference (WMD) with 95% confidence interval (CI) was calculated for these outcomes. The efficacy of steroids was investigated in quantitative, oxygen, steroid plus erythropoietin (EPO), levodopa/carbidopa, memantine, and heparin-induced extracorporeal LDL/fibrinogen precipitation (HELP) therapies and other therapeutic modalities in qualitative synthesis. RESULTS: Thirty-two studies were found to be eligible. We found that steroid therapy compared to control did not improve VA (p = 0.182, WMD = 0.14, 95% CI: -0.07, 0.35) or VF (p = 0.853, WMD = 0.16, 95% CI: -1.54, 1.86). Qualitative analysis could be performed for oxygen, steroid plus EPO, and HELP as well, however, none of them showed VA and VF benefit. Two individual studies found memantine and levodopa beneficial regarding VA. CONCLUSION: Our systematic review did not reveal any effective treatment. Further investigations are needed to find therapy for NAION.

Weight reduction added to CPAP decreases blood pressure and triglyceride level in OSA: Systematic review and meta-analysis.

Obstructive sleep apnea (OSA) is associated with treatment-resistant hypertension and high cardiovascular risk. Continuous positive airway pressure (CPAP) fails to reduce cardiovascular risks consistently. Obesity and OSA show reciprocal association and they synergistically increase hypertension via different pathways. Our meta-analysis aimed to assess the cardiovascular benefits of combining weight loss (WL) with CPAP (vs. WL or CPAP alone) in OSA. Outcomes included systolic and diastolic blood pressure (BP) and blood lipid parameters. We explored Medline, Embase, Cochrane, and Scopus. Eight randomized controlled studies (2627 patients) were included. The combined therapy decreased systolic BP more than CPAP alone. Weighted mean difference (WMD) for CPAP + WL versus CPAP was -8.89 mmHg, 95% confidence interval (95% CI; -13.67 to -4.10, p < 0.001) for systolic BP. For diastolic BP, this decrease was not significant. In case of blood lipids, the combined treatment decreased triglyceride levels more than CPAP alone (WMD = -0.31, 95% CI -0.58 to -0.04, p = 0.027). On the other hand, addition of CPAP to WL failed to suppress BP further. The certainty of evidence according to GRADE was very low to moderate. In conclusion, our results showed that the addition of WL to CPAP significantly improved BP and blood lipid values in OSA. On the other hand, the addition of CPAP to WL could not significantly improve BP or blood lipid values. Review protocol: PROSPERO CRD42019138998.

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.

Stereolithography 3D Printing of a Heat Exchanger for Advanced Temperature Control in Wire Myography.

We report the additive manufacturing of a heat-exchange device that can be used as a cooling accessory in a wire myograph. Wire myography is used for measuring vasomotor responses in small resistance arteries; however, the commercially available devices are not capable of active cooling. Here, we critically evaluated a transparent resin material, in terms of mechanical, structural, and thermal behavior. Tensile strength tests (67.66 ± 1.31 MPa), Charpy impact strength test (20.70 ± 2.30 kJ/m2), and Shore D hardness measurements (83.0 ± 0.47) underlined the mechanical stability of the material, supported by digital microscopy, which revealed a glass-like structure. Differential scanning calorimetry with thermogravimetry analysis and thermal conductivity measurements showed heat stability until ~250 °C and effective heat insulation. The 3D-printed heat exchanger was tested in thermophysiology experiments measuring the vasomotor responses of rat tail arteries at different temperatures (13, 16, and 36 °C). The heat-exchange device was successfully used as an accessory of the wire myograph system to cool down the experimental chambers and steadily maintain the targeted temperatures. We observed temperature-dependent differences in the vasoconstriction induced by phenylephrine and KCl. In conclusion, the transparent resin material can be used in additive manufacturing of heat-exchange devices for biomedical research, such as wire myography. Our animal experiments underline the importance of temperature-dependent physiological mechanisms, which should be further studied to understand the background of the thermal changes and their consequences.

Dietary supplementation of transient receptor potential vanilloid-1 channel agonists reduces serum total cholesterol level: a meta-analysis of controlled human trials.

Abnormal cholesterol level is a major risk factor in the development of atherosclerosis, which is a fundamental derangement in cardiovascular diseases. Any efforts should be undertaken to lower blood cholesterol levels. Among dietary interventions, capsaicinoid supplementation is also considered as a novel cholesterol-lowering approach, but human studies concluded contradictory results about its effectiveness. The present meta-analysis aimed at determining the effects of capsaicinoids on serum lipid profile in humans. We searched the PubMed, EMBASE, and CENTRAL databases from inception to February 2021. We included 10 controlled studies, which involved 398 participants. We found that dietary capsaicinoid supplementation alone or in combination with other substances significantly (p = 0.004 and 0.001, respectively) reduced serum total cholesterol level compared to controls with an overall standardized mean difference of -0.52 (95% confidence interval: -0.83, -0.21). Capsaicinoids also decreased low-density lipoprotein level significantly (p = 0.035), whereas no effect was observed on serum levels of high-density lipoprotein and triglycerides. Our findings provide novel quantitative evidence for the efficacy of dietary capsaicin supplementation in lowering serum total cholesterol and low-density lipoprotein levels in humans. To validate our conclusion, further randomized controlled trials in a diverse population of adult humans receiving dietary capsaicinoid supplementation are warranted.

The hyperthermic effect of central cholecystokinin is mediated by the cyclooxygenase-2 pathway.

Cholecystokinin (CCK) increases core body temperature via CCK2 receptors when administered intracerebroventricularly (icv). The mechanisms of CCK-induced hyperthermia are unknown, and it is also unknown whether CCK contributes to the fever response to systemic inflammation. We studied the interaction between central CCK signaling and the cyclooxygenase (COX) pathway. Body temperature was measured in adult male Wistar rats pretreated with intraperitoneal infusion of the nonselective COX enzyme inhibitor metamizol (120 mg/kg) or a selective COX-2 inhibitor, meloxicam, or etoricoxib (10 mg/kg for both) and, 30 min later, treated with intracerebroventricular CCK (1.7 µg/kg). In separate experiments, CCK-induced neuronal activation (with and without COX inhibition) was studied in thermoregulation- and feeding-related nuclei with c-Fos immunohistochemistry. CCK increased body temperature by ∼0.4°C from 10 min postinfusion, which was attenuated by metamizol. CCK reduced the number of c-Fos-positive cells in the median preoptic area (by ∼70%) but increased it in the dorsal hypothalamic area and in the rostral raphe pallidus (by ∼50% in both); all these changes were completely blocked with metamizol. In contrast, CCK-induced satiety and neuronal activation in the ventromedial hypothalamus were not influenced by metamizol. CCK-induced hyperthermia was also completely blocked with both selective COX-2 inhibitors studied. Finally, the CCK2 receptor antagonist YM022 (10 µg/kg icv) attenuated the late phases of fever induced by bacterial lipopolysaccharide (10 µg/kg; intravenously). We conclude that centrally administered CCK causes hyperthermia through changes in the activity of "classical" thermoeffector pathways and that the activation of COX-2 is required for the development of this response.NEW & NOTEWORTHY An association between central cholecystokinin signaling and the cyclooxygenase-prostaglandin E pathway has been proposed but remained poorly understood. We show that the hyperthermic response to the central administration of cholecystokinin alters the neuronal activity within efferent thermoeffector pathways and that these effects are fully blocked by the inhibition of cyclooxygenase. We also show that the activation of cyclooxygenase-2 is required for the hyperthermic effect of cholecystokinin and that cholecystokinin is a modulator of endotoxin-induced fever.

Inflammatory Biomarkers Are Inaccurate Indicators of Bacterial Infection on Admission in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease-A Systematic Review and Diagnostic Accuracy Network Meta-Analysis.

Introduction: The value of inflammatory biomarkers in the diagnosis of bacterial infection induced acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is currently unclear. Our objective was to investigate the diagnostic accuracy of on-admission inflammatory biomarkers in differentiating bacterial origin in AECOPD. Methods: Systematic literature search was performed to include cross-sectional studies on AECOPD patients with microbiological culture results as gold standard, and at least one on-admission inflammatory biomarker determined from serum: C-reactive protein (CRP), procalcitonin (PCT), neutrophil/lymphocyte ratio, eosinophil percentage, CD64index; or sputum: neutrophil elastase, tumor necrosis factor alfa, interleukin-1-beta (IL-1b), interleukin-8, sputum color, as index tests. We ranked index tests by superiority indices in a network meta-analysis and also calculated pooled sensitivity and specificity. Results: Altogether, 21 eligible articles reported data on 2,608 AECOPD patients (44% bacterial). Out of the 14 index tests, sputum IL-1b showed the highest diagnostic performance with a pooled sensitivity of 74% (CI: 26-97%) and specificity of 65% (CI: 19-93%). Pooled sensitivity for CRP and PCT were: 67% (CI: 54-77%) and 54% (CI: 39-69%); specificity 62% (CI: 52-71%) and 71% (CI: 59-79%), respectively. Conclusion: Admission inflammatory biomarkers are inaccurate indicators of bacterial infection in AECOPD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#myprospero, identifier: 42020161301.