Fever is among the most common symptoms of people living in Africa, and clinicians are challenged by the similar clinical features of a wide spectrum of potential aetiologies.
To summarize recent ...studies of fever aetiology in sub-Saharan Africa focusing on causes other than malaria.
A narrative literature review by searching the MEDLINE database, and recent conference abstracts.
Studies of multiple potential causes of fever are scarce, and for many participants the infecting organism remains unidentified, or multiple co-infecting microorganisms are identified, and establishing causation is challenging. Among ambulatory patients, self-limiting arboviral infections and viral upper respiratory infections are common, occurring in up to 60% of children attending health centres. Among hospitalized patients there is a high prevalence of potentially fatal infections requiring specific treatment. Bacterial bloodstream infection and bacterial zoonoses are major causes of fever. In recent years, the prevalence of antimicrobial resistance among bacterial isolates has increased, notably with spread of extended spectrum β-lactamase-producing Enterobacteriaceae and fluoroquinolone-resistant Salmonella enterica. Among those with human immunodeficiency virus (HIV) infection, Mycobacterium tuberculosis bacteraemia has been confirmed in up to 34.8% of patients with sepsis, and fungal infections such as cryptococcosis and histoplasmosis remain important.
Understanding the local epidemiology of fever aetiology, and the use of diagnostics including malaria and HIV rapid-diagnostic tests, guides healthcare workers in the management of patients with fever. Current challenges for clinicians include assessing which ambulatory patients require antibacterial drugs, and identifying hospitalized patients infected with organisms that are not susceptible to empiric antibacterial regimens.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Perioperative neurocognitive disorders (PND) result in long-term morbidity and mortality with no effective interventions available. Because interleukin-6 (IL-6), a pro-inflammatory cytokine, is ...consistently up-regulated by trauma, including after surgery, we determined whether IL-6 is a putative therapeutic target for PND in a mouse model.
Following institutional approval, adult (12–14 weeks) male C57/Bl6 mice were pretreated with the IL-6 receptor (IL6R) blocking antibody tocilizumab prior to open tibia fracture with internal fixation under isoflurane anaesthesia. Inflammatory and behavioural responses in a trace fear conditioning (TFC) paradigm were assessed postoperatively. Separately, the effects of IL-6 administration or of depletion of bone marrow-derived monocytes (BM-DMs) with clodrolip on the inflammatory and behavioural responses were assessed. Blood brain barrier disruption, hippocampal microglial activation, and infiltration of BM-DMs were each assessed following IL-6 administration.
The surgery-induced decrement in freezing time in the TFC assay, indicative of cognitive decline, was attenuated by tocilizumab (P<0.01). The surgery-induced increase in pro-inflammatory mediators was significantly reduced by tocilizumab. Exogenously administered IL-6 significantly impaired freezing behaviour (P<0.05) and up-regulated pro-inflammatory cytokines; both responses were prevented by depletion of BM-DMs. IL-6 disrupted the blood brain barrier, and increased hippocampal activation of microglia and infiltration of BM-DMs.
IL-6 is both necessary and sufficient to produce cognitive decline. Following further preclinical testing of its perioperative safety, the IL6R blocker tocilizumab is a candidate for prevention and/or treatment of PND.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Postoperative delirium is prevalent in older patients and associated with worse outcomes. Recent data in animal studies demonstrate increases in inflammatory markers in plasma and cerebrospinal fluid ...(CSF) even after aseptic surgery, suggesting that inflammation of the central nervous system may be part of the pathogenesis of postoperative cognitive changes. We investigated the hypothesis that neuroinflammation was an important cause for postoperative delirium and cognitive dysfunction after major non-cardiac surgery.
After Institutional Review Board approval and informed consent, we recruited patients undergoing major knee surgery who received spinal anesthesia and femoral nerve block with intravenous sedation. All patients had an indwelling spinal catheter placed at the time of spinal anesthesia that was left in place for up to 24 h. Plasma and CSF samples were collected preoperatively and at 3, 6, and 18 h postoperatively. Cytokine levels were measured using ELISA and Luminex. Postoperative delirium was determined using the confusion assessment method, and cognitive dysfunction was measured using validated cognitive tests (word list, verbal fluency test, digit symbol test).
Ten patients with complete datasets were included. One patient developed postoperative delirium, and six patients developed postoperative cognitive dysfunction. Postoperatively, at different time points, statistically significant changes compared to baseline were present in IL-5, IL-6, I-8, IL-10, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, IL-6/IL-10, and receptor for advanced glycation end products in plasma and in IFN-γ, IL-6, IL-8, IL-10, MCP-1, MIP-1α, MIP-1β, IL-8/IL-10, and TNF-α in CSF.
Substantial pro- and anti-inflammatory activity in the central neural system after surgery was found. If confirmed by larger studies, persistent changes in cytokine levels may serve as biomarkers for novel clinical trials.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Introduction
For a drug that has been omnipresent for nearly 200 years, nitrous oxide’s (N2O) future seems less certain than its illustrious past. Environmental concerns are coming to the ...fore and may yet outweigh important clinical benefits.
Sources of data
After determining the scope of the review, the authors used PubMed with select phrases encompassing the words in the scope. Both preclinical and clinical reports were considered.
Areas of agreement
The analgesic and anaesthetic advantages of N2O remain despite a plethora of newer agents
Areas of controversy
N2O greenhouse gas effect and its inhibition of key enzymes involved in protein and DNA synthesis have provided further fuel for those intent on eliminating its further clinical use.
Growing points
The use of N2O for treatment-resistant depression has gained traction.
Areas timely for developing research
Comparative studies for N2O role in combatting the prescription opioid analgesic epidemic may well provide further clinical impetus.
The demographics of aging of the surgical population has increased the risk for perioperative neurocognitive disorders in which trauma-induced neuroinflammation plays a pivotal role.
After ...determining the scope of the review, the authors used PubMed with select phrases encompassing the words in the scope. Both preclinical and clinical reports were considered.
Neuroinflammation is a sine qua non for development of perioperative neurocognitive disorders.
What is the best method for ameliorating trauma-induced neuroinflammation while preserving inflammation-based wound healing.
This review considers how to prepare for and manage the vulnerable elderly surgical patient through the entire spectrum, from preoperative assessment to postoperative period.
What are the most effective and safest interventions for preventing and/or reversing Perioperative Neurocognitive Disorders.
Background: Recent evidence has demonstrated the anti‐apoptotic of dexmedetomidine in different brain injury models. Herein, we investigated whether dexmedetomidine could directly protect against ...cortical injury in vitro and in vivo.
Methods: Apoptosis was induced by staurosporine or wortmannin treatment in cortical neuronal cultures in vitro or by 6 h of isoflurane (0.75%) administration to post‐natal day 7 rat pups in vivo. Dexmedetomidine was then applied in escalating doses to assess the neuroprotective potential of this agent. Cell survival was quantified using an MTT assay in vitro and in vivo apoptosis was assessed using cleaved caspase‐3 immunohistochemistry. Cortical Western blots were conducted for the cellular survival proteins Bcl‐2 and phosphorylated extracellular signal‐regulated protein kinase (pERK)1 and 2.
Results: In vitro dexmedetomidine dose‐dependently prevented both staurosporine‐ and wortmannin‐induced injury in cortical neuronal cultures, indicating that dexmedetomidine can prevent apoptosis when applied directly. In vivo isoflurane induced cortical neuroapoptosis compared with air (327±80 vs. 34±9 caspase‐3‐positive neurons; P<0.05). Dexmedetomidine inhibited isoflurane‐induced caspase‐3 expression (P<0.05), although the protection achieved did not completely attenuate the isoflurane injury (P<0.05 vs. air). Isoflurane treatment decreased Bcl‐2 and pERK protein expression relative to air, an effect reversed by dexmedetomidine treatment.
Conclusions: Dexmedetomidine prevents cortical apoptosis in vitro and in vivo. However, using higher doses of dexmedetomidine does not further increase protection against isoflurane injury in the cortex than previously observed.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
The escalation in the prevalence of obesity throughout the world has led to an upsurge in the number of obese surgical patients to whom perioperative care needs to be delivered.
After determining the ...scope of the review, the authors used PubMed with select phrases encompassing the words in the scope. Both preclinical and clinical reports were considered.
There were no controversies regarding preoperative management and the intraoperative care of the obese surgical patient.
Is there a healthy obese state that gives rise to the obesity paradox regarding postoperative complications?
This review considers how to prepare for and manage the obese surgical patient through the entire spectrum, from preoperative assessment to possible postoperative intensive care.
What results in an obese patient developing 'unhealthy' obesity?
Objective
Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described ...this systemic‐to‐brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short‐ and long‐term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function.
Methods
Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using 11CPBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed.
Results
Patients showed a global downregulation of gray matter 11CPBR28 binding of 26 ± 26% (mean ± standard deviation) at 3 to 4 days postoperatively compared to baseline (p = 0.023), recovering or even increasing after 3 months. LPS‐induced release of the proinflammatory marker tumor necrosis factor‐α in blood displayed a reduction (41 ± 39%) on the 3rd to 4th postoperative day, corresponding to changes in 11CPBR28 distribution volume. Change in Stroop Color‐Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in 11CPBR28 binding (p = 0.027).
Interpretation
This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function. Ann Neurol 2017;81:572–582
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We investigated the role of regionally discrete GABA (gamma-aminobutyric acid) receptors in the sedative response to pharmacological agents that act on GABA(A) receptors (muscimol, propofol and ...pentobarbital; 'GABAergic agents') and to ketamine, a general anesthetic that does not affect GABA(A) receptors. Behavioral studies in rats showed that the sedative response to centrally administered GABAergic agents was attenuated by the GABA(A) receptor antagonist gabazine (systemically administered). The sedative response to ketamine, by contrast, was unaffected by gabazine. Using c-Fos as a marker of neuronal activation, we identified a possible role for the tuberomammillary nucleus (TMN): when gabazine was microinjected directly into the TMN, it attenuated the sedative response to GABAergic agents. Furthermore, the GABA(A) receptor agonist muscimol produced a dose-dependent sedation when it was administered into the TMN. We conclude that the TMN is a discrete neural locus that has a key role in the sedative response to GABAergic anesthetics.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Leptospirosis is under-diagnosed by clinicians in many high-incidence countries, because reference diagnostic tests are largely unavailable. Lateral flow assays (LFA) that use antigen derived from ...heat-treated whole cell Leptospira biflexa serovar Patoc have the potential to improve leptospirosis diagnosis in resource-limited settings.
We sought to summarize estimates of sensitivity and specificity of LFA by conducting a systematic review and meta-analysis of evaluations of the accuracy of LFA to diagnose human leptospirosis.
On 4 July 2017 we searched three medical databases.
Study eligibility criteriaArticles were included if they were a study of LFA sensitivity and specificity.
Patients with suspected leptospirosis.
Nil.
For included articles, we assessed study quality, characteristics of participants and diagnostic testing methods. We estimated sensitivity and specificity for each study against the study-defined case definition as the reference standard, and performed a meta-analysis using a random-effects bivariate model.
Our search identified 225 unique reports, of which we included nine (4%) published reports containing 11 studies. We classified one (9%) study as high quality. Nine (82%) studies used reference tests with considerable risk of misclassification. Our pooled estimates of sensitivity and specificity were 79% (95% CI 70%–86%) and 92% (95% CI 85%–96%), respectively.
As the evidence base for determining the accuracy of LFA is small and at risk of bias, pooled estimates of sensitivity and specificity should be interpreted with caution. Further studies should use either reference tests with high sensitivity and specificity or statistical techniques that account for an imperfect reference standard.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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