Scientific reports
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Avian-origin H5/H7 influenza has the potential to cause the next influenza pandemic. Availability of effective vaccines is an essential part of pre-pandemic preparedness. However, avian influenza surface antigens are poorly immunogenic to humans, which necessitates the use of adjuvants to augment the immunogenicity of pre-pandemic influenza vaccines. ⋯ The weighted estimate for the risk ratio of pain/tenderness at injection sites is 1.85 (95% CI: 1.56 to 2.19). The quality of evidence is low to very low for seroprotection (due to indirectness and potential reporting bias) and moderate for pain/tenderness (due to potential reporting bias), respectively. The significantly lower seroprotection rate after aluminum-adjuvanted H5N1 vaccines and the significantly higher risk of pain at injection sites indicate that aluminum salts decrease immunogenicity but increase local reactogenicity of pre-pandemic H5N1 vaccines in humans.
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Measurements of skeletal muscle cross-sectional area, index, and radiation attenuation utilizing clinical computed tomography (CT) scans are used in assessments of sarcopenia, the loss of skeletal muscle mass and function associated with aging. To classify individuals as sarcopenic, sex-specific cutoffs for 'low' values are used. Conventionally, cutoffs for skeletal muscle measurements at the level of the third lumbar (L3) vertebra are used, however L3 is not included in several clinical CT protocols. ⋯ SMA peaks at L3, supporting its use as the primary site for CT sarcopenia measurements. However, when L3 is not available alternative levels (in order of preference) are L2, L4, L5, L1, T12, T11, and T10. Healthy reference values reported here enable sarcopenia assessment and sex-specific standardization of SMA, SMI, and SMRA in clinical populations, including those whose CT protocols do not include L3.
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Feasibility of ED triage sepsis screening, before diagnostic testing has been performed, has not been established. In a retrospective, outcome-blinded chart review of a one-year cohort of ED adult septic shock patients ("derivation cohort") and three additional, non-consecutive months of all adult ED visits ("validation cohort"), we evaluated the qSOFA score, the Shock Precautions on Triage (SPoT) vital-signs criterion, and a triage concern-for-infection (tCFI) criterion based on risk factors and symptoms, to screen for sepsis. There were 19,670 ED patients in the validation cohort; 50 developed ED septic shock, of whom 60% presented without triage hypotension, and 56% presented with non-specific symptoms. ⋯ At triage, sepsis screens (positive qSOFA vital-signs and tCFI, or positive SPoT vital-signs and tCFI) were 28% (95% CI: 16-43%) and 56% (95% CI: 41-70%) sensitive, respectively, p < 0.01. By the conclusion of the ED stay, sensitivities were 80% (95% CI: 66-90%) and 90% (95% CI: 78-97%), p > 0.05, and specificities were 97% (95% CI: 96-97%) and 95% (95% CI: 95-96%), p < 0.001. ED patients who developed septic shock requiring vasopressors often presented normotensive with non-specific complaints, necessitating a low threshold for clinical concern-for-infection at triage.
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Contact heat evoked potentials (CHEPs) have become an acknowledged research tool in the assessment of the integrity of the nociceptive system and gained importance in the diagnostic work-up of patients with suspected small fiber neuropathy. For the latter, normative values for CHEP amplitude and latency are indispensable for a clinically meaningful interpretation of the results gathered in patients. To this end, CHEPs were recorded in 100 healthy subjects over a wide age range (20-80 years) and from three different dermatomes of the lower extremities (L2, L5, and S2). ⋯ Significant positive correlations of body height with N2 latency, and pain ratings with N2P2 amplitudes were observed. This is the first time that normative values have been obtained from multiple dermatomes of the lower extremities. The present dataset will facilitate the clinical application of CHEPs in the neurophysiological diagnosis of small fiber neuropathy and by discerning pathological findings help establish a proximal-distal gradient of nerve degeneration in polyneuropathies.
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Neuropathic pain typically appears in a region innervated by an injured or diseased nerve and, in some instances, also on the contralateral side. This so-called mirror image pain is often observed in mice lacking CB2 receptors after sciatic nerve injury, but the underlying mechanisms for this phenotype largely remain unclear. Here we focused on peripheral leptin signaling, which modulates neuropathic pain development and interacts with the endocannabinoid system. ⋯ Interestingly, an upregulation of leptin receptor expression STAT3 activity and macrophage infiltration was also observed on the non-injured nerve of CB2-KO mice thus reflecting the mirror image pain in CB2-KO animals. Importantly, perineurally-administered leptin-neutralizing antibodies reduced mechanical hyperalgesia, blocked mirror image pain and inhibited the recruitment of F4/80-positive macrophages. These results identify peripheral leptin signaling as an important modulator of CB2 signaling in neuropathic pain.