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Background: Water-filtered infrared-A (wIRA) is a special form of heat radiation with high tissue penetration and a low thermal load to the skin surface. wIRA corresponds to the major part of the sun’s heat radiation, which reaches the surface of the Earth in moderate climatic zones filtered by water and water vapour of the atmosphere. wIRA promotes healing of acute and chronic wounds both by thermal and thermic as well as by non-thermal and non-thermic cellular effects.
Methods: This publication includes a literature review with search in PubMed/Medline for “water-filtered infrared-A” and “wound”/”ulcus” or “wassergefiltertes Infrarot A” and “Wunde”/”Ulkus”, respectively (publications in English and German), and additional analysis of study data. Seven prospective clinical studies (of these six randomized controlled trials (RCT), the largest study with n=400 patients) were identified and included. All randomized controlled clinical trials compare a combination of high standard care plus wIRA treatment vs. high standard care alone. The results below marked with “vs.” present these comparisons.
Results:
* wIRA increases tissue temperature (+2.7°C at a tissue depth of 2 cm), tissue oxygen partial pressure (+32% at a tissue depth of 2 cm) and tissue perfusion (effect sizes within the wIRA group).
* wIRA promotes normal as well as disturbed wound healing by diminishing inflammation and exudation, by promotion of infection defense and regeneration, and by alleviation of pain (with respect to alleviation of pain, without any exception during 230 irradiations, 13.4 vs. 0.0 on a visual analogue scale (VAS 0–100), median difference between groups 13.8, 95% confidence interval (CI) 12.3/16.7, p<0.000001) with a substantially reduced need for analgesics (52–69% less in the three groups with wIRA compared to the three control groups in visceral surgery, p=0.000020 and 0.00037 and 0.0045, respectively; total of 6 vs. 14.5 analgesic tablets on 6 surveyed days (of weeks 1–6) in chronic venous stasis ulcers, median difference –8, 95% CI –10/–5, p=0.000002).
Further effects are:
* Faster reduction of wound area (in severely burned children: 90% reduction of wound size after 9 vs. 13 days, after 9 days 89.2% vs. 49.5% reduction in wound area, median difference 39.5% wound area reduction, 95% CI 36.7%/42.2%, p=0.000011; complete wound closure of chronic venous stasis ulcers after 14 vs. 42 days, median difference –21 days, 95% CI –28/–10, p=0.000005).
* Better overall evaluation of wound healing (surgical wounds: 88.6 vs. 78.5 on a VAS 0–100, median difference 8.9, 95% CI 6.1/12.0, p<0.000001).
* Better overall evaluation of the effect of irradiation (79.0 vs. 46.8 on a VAS 0–100 with 50 as neutral point, median difference 27.9, 95% CI 19.8/34.6, p<0.000001).
* Higher tissue oxygen partial pressure during irradiation with wIRA (at a tissue depth of 2 cm 41.6 vs. 30.2 mmHg, median difference 11.9 mmHg, 95% CI 9.6/14.2 mmHg, p<0.000001).
* Higher tissue temperature during irradiation with wIRA (at a tissue depth of 2 cm 38.9 vs. 36.4°C, median difference 2.6°C, 95% CI 2.2/2.9°C, p<0.000001).
* Better cosmetic result (84.5 vs. 76.5 on a VAS 0–100, median difference 7.9, 95% CI 3.7/12.0, p=0.00027).
* Lower wound infection rate (single preoperative irradiation: 5.1% vs. 12.1% wound infections in total, difference –7.0%, 95% CI –12.8%/–1.3%, p=0.017, of these: late wound infections (postoperative days 9-30) 1.7% vs. 7.7%, difference –6.0%, 95% CI –10.3%/–1.7%, p=0.007).
* Shorter hospital stay (9 vs. 11 postoperative days, median difference –2 days, 95% CI –3/0 days, p=0.022).
Most of the effects have been proven with an evidence level of 1a or 1b.
Conclusion: Water-filtered infrared-A is a useful complement for the treatment of acute and chronic wounds.
Keywords: water-filtered infrared-A (wIRA), wound healing, acute and chronic wounds, reduction of pain, tissue oxygen partial pressure, tissue temperature
Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ~2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the Xchromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p = 5.87×10-9; odds ratio = 1.12) and markers within ERBB2 (rs2517959, p = 4.53×10-9; odds ratio = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
R-flurbiprofen is the non-COX-inhibiting enantiomer of flurbiprofen and is not converted to S-flurbiprofen in human cells. Nevertheless, it reduces extracellular prostaglandin E2 (PGE2) in cancer or immune cell cultures and human extracellular fluid. Here, we show that R-flurbiprofen acts through a dual mechanism: (i) it inhibits the translocation of cPLA2α to the plasma membrane and thereby curtails the availability of arachidonic acid and (ii) R-flurbiprofen traps PGE2 inside of the cells by inhibiting multidrug resistance–associated protein 4 (MRP4, ABCC4), which acts as an outward transporter for prostaglandins. Consequently, the effects of R-flurbiprofen were mimicked by RNAi-mediated knockdown of MRP4. Our data show a novel mechanism by which R-flurbiprofen reduces extracellular PGs at physiological concentrations, particularly in cancers with high levels of MRP4, but the mechanism may also contribute to its anti-inflammatory and immune-modulating properties and suggests that it reduces PGs in a site- and context-dependent manner.