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Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_764_Библиотеки_им_академика_М_И_Перельмана

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F. Malan
The therapeutic effect of light due to the pres­ence in the tissues of endogenous molecules capable of absorbing it occurs because the energy conveyed by the light beam is absorbed by ele­ments naturally present in the tissues, called “chromophores,” and used to promote chemical reactions or produce conformational changes in some biomolecules.
This treatment brings therapeutic benets on inammation and pain by promoting wound healing and tissue regeneration.
These discoveries have produced a wave of enthusiasm for a simple and relatively inexpen­sive therapy that is undoubtedly effective in most cases.
Numerous authoritative colleagues have pre­sented various case histories of signicant suc­cesses in the treatment of ulcers of various origins with blue light.
The range of pathologies studied is wide: chronic skin lesions such as ulcers of the lower limbs (venous, arterial, and mixed ulcers), inam­matory ulcers (from rheumatic diseases and scleroderma), diabetic foot and pressure ulcers, and skin lesions with extensive loss of substance such as burns and trauma wounds, surgical dehis­cence, and dermatological disorders. Thanks to this activity, it was found that blue light, through the photobiomodulation process, is able to resolve inammation and stimulate the regenera­tion process of skin tissue.
Inammation is a necessary phase of the wound repair process that should last as a whole no more than 4 weeks; due to pathologies or par­ticular physical conditions (such as advanced age, nutritional deciencies, and mobility restric­tions), the inammatory phase may stall, causing the wound to become chronic. The most wide­spread and impacting chronic wound etiologies are as follows: Ulcers of the lower limbs, origi­nating mainly from venous insufciency, afict 1% of the adult population and 3.6% of the popu­lation over 65years of age; diabetic foot affects one in three patients with diabetes mellitus and is the most frequent cause of lower limb amputation worldwide; and pressure ulcers or “decubitus” is caused by the pressure of a bone pre-eminence in people with limited mobility such as patients in
intensive care, which have an average prevalence estimated in the European population of 13.7%.
An inammatory response, when it is not reg­ulated, is also at the origin of the complication of wounds characterized by extensive loss of sub­stance, originating from trauma or a burn, and surgical dehiscence.
Photobiomodulation with blue light, a ther­apy able to stimulate the transition of the inam­matory phase, can make a contribution to the resolution of wounds with a slowed or never­ending healing process, an important medical– health problem given the high management costs and poor quality of life of patients affected by this problem. As with any innovation, particu­larly in the medical eld, there is a risk of over­estimating its benets, which leads to forcing indications and consequently increasing the fail­ure rate. Therefore, it is worth evaluating the benets and issues related to photobiomodula­tion to improve its use and avoid improper or useless use [3].
The possibility of using photobiomodulation on an outpatient basis is certainly an advantage even if it still requires dedicated time and space, or in any case such as to allow an appropriate use of the equipment, despite a good ease of use. An advantage, already mentioned previously, is cer­tainly given by the relatively low cost of the treatments.
An advantage, certainly important in an era in which ecological sensitivity is also increasing in the health eld, is given by the production of almost zero waste, which translates into signi­cant environmental and economic benets.
The use of photobiomodulation is practically free of contraindications; however, it is not rec­ommended in patients with neoplastic diseases and, obviously, in patients with abnormal sensi­tivity to light, for example, in the case of some porphyrias.
As for the benets, there is no uniformity of results between the various studies conducted on the subject.
Two studies carried out in Tuscany and Piedmont provided signicantly different data on the benets of the treatment of skin ulcers of dif­ferent origins.
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A study by Dini etal., published in 2020 by Minerva Medica, states that after 4 weeks of treatment the healing rate was 0.089mm per day for venous ulcers and 0.353mm per day for trau­matic ulcers, while in another study, also pub­lished by Minerva Medica, from 2021, Fraccalvieri etal. afrm that after 10 weeks sig­nicant improvements have been observed, especially in ulcers of venous origin in a picture, however, of better efcacy than standard thera­pies [4, 5].
The limitation of these studies is given by the fact that they are not multicentered, which can lead to various biases related to the types of stan­dard treatments, the type of patients, and the ref­erence center itself [6, 7].
In essence, however, it can be said that photo­biomodulation is a safe method, with low costs and substantially free of contraindications, which provides, on average, favorable results [810].
In the presence of these characteristics, the main risk is to force the indications with conse­quent lack or insufciency of results with waste of time and slowdowns in the healing processes.
The selection of patients is fundamental, as always, for a correct application of the treatment [1113].
In perspective, the development of multi­centered studies and an accurate meta-analysis of the available data are the main streets to fol­low in order to draw up precise treatment proto­cols and for a selection of patients that optimize the use and benets of photobiomodulation [1418].
Focusing on the photodynamic therapy, it acts using 3 independent agents: light, molecu­lar oxygen and a photosensitized agent. It is based on the application of a non-toxic dye (the photosensitized agent) only on the wound bed (it shouldn’t touch the health skin). The gel needs 30 minutes to be activated and during this time the wound should be covered with a sterile gauze. Then, uncover the wound and expose to the light, the irradiation time is of 8 minutes.
The light source has to stay 10cm distant from the wound bed, it emits a non-coherent light radiation with a peak at 630 nm. The irradiator doesn’t have to touch the wound. At the end of the procedure wash with physiological solution to remove the gel. During the procedure patient and operator should wear protector glasses. The most used light source is the one that generates a red wave spectrum with a high potential of tissue penetration. The photosensitized agent applied on the wound bed absorbs the light and then it activates and transfers energy and elec­trons to the molecular oxygen. The molecular oxygen is now excited to a superior level and it creates the ROS (reactive oxygen species). Once the ROS ties on the cellular membrane of the pathogenic agents, they cause their break­ing but do not damage the non-pathogenic cells of the organism. This is explained by the action of ROS toward the ionic ties present in a higher percentage in the pathogenic cells. When the cells that needs to be killed are pathogenic microorganisms we can talk about “photody­namic inactivation”. This mechanism at the base of the PDT works on the following microorganisms: GRAM+ and GRAM­bacteria, S. Aureus, MRSA, Pseudomonas Aeruginosa, Streptococcus Pyogenes, Propionibacterium Acnes, Corynebacterium minutissimum, Candida albicans, skin fungus, virus, protozoans and biolm.
Photodynamic therapy can be used for the
treatment of the following illness:
• Chronic wounds
• BCC skin cancer
• Post-surgery wounds
• Surgical scars
• Non-hypertrophic actinic keratosis
• Acne Vulgaris
• Teeth infections
• Psoriasis
The PDT helps in different ways the healing process causing cellular death, modulating the inammation process, stimulating the broblast
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and supporting the deposition of collagen and elastin. In addition, it also:
• Increases the ulcers healing
• Reduces the local microbic load and the infection
• Works on every microorganism including the resistant strain in biolm and planktonic form
• Doesn’t induce any bacterial resistance and reduces the necessity of systemic medications
• Improves the scar result
• Is a safe and well-tolerate technique
• Doesn’t cause any pain and it easy to use, so it is possible to use in an outpatient setting As every procedure, also PDT has some con-
traindications and possible adverse effects:
• The product doesn’t have to be used if there is a known hypersensitivity to one of the components
• Do not use the product if other topic dressing are already applied on the wound bed, such as hydrogel, silver bandage, antibiotics, soaps etc. the use of these products should be stopped before the treatment
• This treatment used on health skin can cause redness and temporary rush
• Some patients may refer a complaint and heat during the procedure but is stops at the end of the treatment
• A green coloration of the skin may persist in the application site for a couple of weeks
• Due to the lack of clinical study, it shouldn’t be used in patients with less than 18 years old and during pregnancy and breast feeding
References
1. Aliquò MS, et al. Clinical application of photobio­modulation with blue light on non-healing ulcers in diabetic patients: a case series study. Wounds Int. 2021;12:4.
2. Anders JJ, et al. Low-level light/laser therapy ver­sus photobiomodulation therapy. Photomed Laser Surg. 2015;33(4):183–4. https://doi.org/10.1089/
pho.2015.9848.
3. Cicchi R, et al. Observation of an improved heal­ing process in supercial skin wounds after irra­diation with a blue-LED haemostatic device. J
Biophotonics. 2016;9(6):645–55. https://doi.
org/10.1002/jbio.201500191.
4. Dini V, et al. Blue light emission in the manage­ment of hard-to-heal wounds. Ital J Dermatol Venereol. 2020;155:709. https://doi.org/10.23736/
S0392- 0488.20.06691- 2.
5. Fraccalvieri M, et al. Effectiveness of blue light photobiomodulation therapy in the treatment of chronic wounds. Results of the blue light for ulcer reduction (B.L.U.R.) study. Ital J Dermatol Venerol. 2021;157(2):187. https://doi.org/10.23736/
S2784- 8671.21.07067- 5.
6. Han G, Ceilley R.Chronic wound healing: a review of current management and treatments. Adv Ther. 2017;34(3):599–610. https://doi.org/10.1007/
s12325- 017- 0478- y.
7. Khoo VB, et al. Use of blue light in the manage­ment of chronic venous ulcer in Asian patients: a case series. Cureus. 2021;13(9):e17703. https://doi.
org/10.7759/cureus.17703.
8. Nair HK, Bin Sulong MAA.Effects of photobiomod­ulation with blue light on diabetic foot ulcers: a case series report. Wounds Asia. 2021;4(3):42–7.
9. Magni G, etal. Blue LED light modulates inamma­tory inltrate and improves the healing of supercial wounds. Photodermatol Photoimmunol Photomed. 2019;1:1–3. https://doi.org/10.1111/phpp.12527.
10. Magni M, et al. Experimental study on blue light interaction with human keloid-derived broblasts. Biomedicines. 2020;8:573. https://doi.org/10.3390/
biomedicines8120573.
11. Marchelli M, et al. Photobiomodulation with blue light in non-healing wounds: case series evaluation. Wounds Int. 2019;10(3):63–7.
12. Moore Z, etal. The prevalence of pressure ulcers in Europe, what does the European data tell us: a sys­tematic review. J Wound Care. 2019;28:11.
13. Mosti G, Gasperini S. Observations made on three patients suffering from ulcers of the lower limbs treated with blue light. Chronic Wound Care Manag Res. 2018;5:23–38. https://doi.org/10.2147/CWCMR.
S172060.
14. Rastogi A, etal. Long term outcomes after incident diabetic foot ulcer: multicenter large cohort prospec­tive study (EDI-FOCUS investigators) epidemiology of diabetic foot complications study: epidemiology of diabetic foot complications study. Diabetes Res Clin Pract. 2020;162:108113.
15. Rossi F, etal. Photobiomodulation of human bro­blasts and keratinocytes with blue light: implications in wound healing. Biomedicines. 2021;9:41. https://
doi.org/10.3390/biomedicines9010041.
16. Shubhangi VA. Chronic leg ulcers: epidemiol­ogy, aetiopathogenesis, and management. Ulcers. 2013;9:413604. https://doi.org/10.1155/2013/413604.
17. Vernaci M, Vernaci PP.Contribution of photonic ther­apies to the healing process of chronic wounds: case studies. Wounds Int. 2020;11:4.
18. Zhang Y, etal. Global disability burdens of diabetes­related lower-extremity complications in 1990 and
2016. Diabetes Care. 2020;43(5):964–74.
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17.1 Laser inWound Care
Light Amplication by Stimulated Emission of Radiation (LASER) is an optoelectronic device capable of emitting a coherent beam of light, according to the IUPAC denition. The rst “maser” was built by Charles Hard Townes, J.P. Gordon, and H.J. Zeiger at Columbia University in 1953. The device was similar to a laser, but concentrated electromagnetic energy in a consid­erably lower frequency range: It used stimulated emission to produce microwave amplication instead of infrared or visible waves. Townes and colleagues’ maser could only deliver minimal power, about 10 nW, but Nikolay Basov and Aleksandr Prokhorov solved the problem by the­orizing and developing a “pumping method” with more than two energy levels [1].
The laser is essentially composed of three parts: (1) an active medium, that is, a material (gas, crystal, and liquid) that emits light; (2) a pumping system, which provides energy to the active medium; and (3) an optical cavity, or opti­cal resonator, which is a light trap. In the laser, the active medium is exploited, which has the ability to emit electromagnetic radiation (pho­tons) when activated. The wavelength of the emission depends on the active medium. The
E. Ricci (*) Difcult Wound Healing Unit, Policlinico Monza, Vercelli, Italia, Italy
active medium, Table17.1, can be gaseous (e.g., carbon dioxide and mixture of helium and neon), liquid (solvents, such as methanol, ethanol, or ethylene glycol, to which chemical dyes such as coumarin, rhodamine, and uorescein are added), or solid (ruby, neodymium, semiconductors, etc.). The pumping system supplies energy (through different optical systems of lamps or electrical stimulation) to the active medium bringing it to excitation with photon emission. The emitted radiation is normally concentrated through an optical cavity with reective inner walls and a semi-reective exit zone. This last surface is the only one that allows the beam to escape, which is subsequently processed and repositioned through a series of lenses and mir­rors to ensure that the resulting beam has the desired position, concentration, and amplitude. The spatial and temporal coherence of the laser beam is related to its main properties: The tempo­ral coherence, that is, the fact that the waves retain the same phase in time, is related to the property of lasers to emit beams of radiation in a very narrow spectral range. It is therefore consid­ered a monochromatic wave. Spatial coherence, i.e., the fact that the phase difference is constant between distinct points in a cross section of the beam, is related to the possibility of having unidi­rectional and collimated beams, that is, parallel even over long paths. Laser beams can be focused on very small areas, even with dimensions of the order of micrometers, impossible with non-
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 M. Maruccia et al. (eds.), Pearls and Pitfalls in Skin Ulcer Management,
https://doi.org/10.1007/978-3-031-45453-0_17
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Table 17.1 Media types and transmission systems
Media Active medium Delivery system Solid state • Ruby
• Nd:YAG
• Ho:YAG
• Er:YAG
• Thulium:YAG
Gas • CO
Semiconductors • Diode Liquid state • Dye Optical ber Chemical • HF
2
• Argon
• Excimer
• HeNe
Optic ber Optical ber Optic ber Optical ber
Articulated arm Optic ber Optic ber
coherent radiation. The unidirectional and coher­ent emission implies the possibility of reaching a very high-power density compared to that of tra­ditional light sources. These properties are the basis of the wide range of applications that laser devices have had and continue to have in the most diverse elds. The higher the frequency (there­fore the lower the wavelength) of the emitted waves, the higher the energy produced by the laser.
Lasers are classied according to the danger to human health. The classication is carried out by the manufacturer according to IEC 60825 standards harmonized in the European Union with CENELEC EN 60825–1 standards. Before 2007, lasers were classied into ve classes (1, 2, 3a, 3b, and 4) depending on power and wave­length, considering that emissions in the visible band were considered less dangerous thanks to eyelid reection. The standards currently in force divide lasers into seven classes [2], introducing the parameters of:
• Accessible Emission Limit (LEA): The maxi-
mum level of accessible emission allowed in a
particular class.
• Maximum Permissible Exposure (MEP): The
level of laser radiation to which, under ordi-
nary conditions, people can be exposed with­out suffering harmful effects. MEP levels represent the maximum level to which the eye or skin can be exposed without suffering short- or long-term damage. The MEP from which the LEA of the different classes of lasers is normally derived was derived from the “Guidelines on exposure limits to laser radiation of wavelengths between 180nm and 1 mm,” which was drawn up by the International Commission on Non-Ionizing Radiation Protection (ICNIRP).
• Nominal Optical Hazard Distance (DNRO): distance from the output aperture where the intensity or energy per unit area (irradiance or radiance quantities) is equal to the maximum exposure allowed to avoid corneal damage (MEP).
The classication is shown in Table17.2. Lasers are classied into high and low power.
The rst is generally applied for the removal, cut­ting, and coagulating of tissues, while the low­power ones are more commonly applied in the processes of tissue repair, such as muscle, joint, nerve, bone, and skin injuries. Lasers are also characterized by the duration of laser emission— continuous wave or pulsed laser. A Q-switched laser is a pulsed laser, which contains a shutter­like device that does not allow the emission of laser light until opened. Energy is built up in a Q-switched laser and released by opening the device to produce a single, intense laser pulse (Table17.3).
When we talk about lasers in medicine, we
can refer to the subdivision of use and denition provided by the American FDA, which is shown here in Table17.4.
The use in our sector can be found in surgical
denitions. In the vulnological eld, we can dene two principal action: debridement with ablator laser and biostimulation with LLLT.
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Table 17.2 Classication of lasers according to risk of injury
Class Description and warnings Wavelength 1 Accessible laser radiation is not dangerous. Lasers with emissions higher than
MEP are class 1A when enclosed in an inaccessible housing
1M Accessible laser radiation is harmless under normal conditions of use until there
are optical instruments such as magnifying glasses or binoculars that can concentrate energy on the cornea. Do not look at the beam directly with
instruments with optical instruments
2 Laser radiation is accessible in the visible spectrum. It is harmless to the eye even
considering that the protection of the eye is normally ensured by defense reactions including the eyelid reex (about o,25s) even if optical observation devices are used. Do not observe the beam
2M Like class 2, beam vision can be more dangerous if the observer employs
observation optics within the beam. Do not x the beam or look at it directly
with optical instruments
3R Accessible laser radiation is potentially hazardous, LEA is less than ve times
LEA class 2in the wavelength range of 400 to 700nm, and less than ve times LEA class 1 for other wavelengths. Avoid direct exposure of the eyes
3 B Accessible laser radiation is normally dangerous for the eyes if exposed at a
distance lower than DNRO and in special cases also for the skin. Exposure to diffused or reection- dispersed light is usually safe. Avoid exposure to beam
4 Accessible laser radiation is very dangerous for the eyes and dangerous for the
skin. Diffuse radiation can also be dangerous. When using this laser, you can cause res or explosions. Avoid exposing eyes or skin to direct or diffuse radiation
180nm–1mm
302,5nm–400nm
400nm–700nm
400nm–700nm
180nm–1mm
180nm–1mm
180nm–1mm
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Table 17.3 Classication of lasers by emission time
Continuous wave (CW)
Single pulsed Lasers generally have pulse durations of a few hundred microseconds to a few milliseconds. This
Single pulsed q-switched
Repetitively pulsed
Mode locked Lasers operate as a result of the resonant modes of the optical cavity, which can affect the
Table 17.4 Different uses of lasers in the medical eld, from FDA classication
Cosmetic surgery
Refractive eye surgery
Dental procedures
General surgery Tumor removal, breast surgery, plastic surgery, debridement, and most other surgical procedures Biostimulation Also called low-level laser therapy (LLLT), cold lasers, soft lasers, or laser acupuncture devices
Lasers operate with a stable average beam power. In most higher-power systems, one is able to adjust the power. In low-power gas lasers, such as HeNe, the power level is xed by design and performance degrades with long-term use
mode of operation is sometimes referred to as long pulse or normal mode Lasers are the result of an intracavity delay (Q-switch cell), which allows the laser media to store a
maximum of potential energy. Then, under optimum gain conditions, emission occurs in single pulses, typically of 10(8)-second time domain. These pulses will have high peak powers often in the range from 10(6) to 10(9) Watts peak
Scanning lasers generally involve the operation of pulsed laser performance operating at a xed (or variable) pulse rates, which may range from a few pulses per second to as high as 20,000 pulses per second. The direction of a CW laser can be scanned rapidly using optical scanning systems to produce the equivalent of a repetitively pulsed output at a given location
characteristics of the output beam. When the phases of different frequency modes are synchronized, i.e., “locked together,” the different modes will interfere with one another to generate a beat effect. The result is a laser output, which is observed as regularly spaced pulsations. Lasers operating in this mode-locked fashion usually produce a train of regularly spaced pulses, each having a duration of 10(15) (femto) to 10(12) (pico) sec. A mode-locked laser can deliver extremely high peak powers than the same laser operating in the Q-switched mode. These pulses will have enormous peak powers often in the range from 10(12) Watts peak
Remove tattoos, scars, stretch marks, sunspots, wrinkles, birthmarks, spider veins, or hair
Reshape the cornea in order to correct or improve vision
Endodontic/periodontic procedures, tooth whitening, and oral surgery, cataract removal
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17.2 Debridement Laser
First of all, we can distinguish two types of lasers depending on the chromophore on which they act:
• Ablators: Elective chromophore water (CO2, holmium, and erbium).
• Coagulators: Elective chromophore hemoglo­bin (argon, krypton, KTP, diodes from 630 to 1500nm, neodymium).
In the literature, there are works that dem-
onstrate the effectiveness of this treatment, and Hajhosseini [3] reports a reduction in bac­terial load and better efficacy than traditional
surgical treatment. Jiang [4] in a randomized trial of 60 patients with surgical debridement vs. debridement on laser CO2 reports better infection control, increased perfusion, and faster repair in the laser group. The same results are reported by Guan [5] and Phillips [6]. In DULCIS 2 [7], using a CO2 scaler on diabetic foot in 118 patients showed an accel­eration of repair times. In vitro, the use of scalers has demonstrated bactericidal and anti­biofilm activity [8, 9].
Ablative lasers are characterized by high pre­cision, high bleeding control, and lower pain than conventional techniques. Figures17.1, 17.2, and
17.3 show some visual examples of interventions
performed using CO2 laser.
Fig. 17.1 Laser tenotomy
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Fig. 17.2 Removal of malacic bone by laser
Fig. 17.3 Biolm ablation by CO2 Laser
17.3 Biostimulation Lasers
Biostimulation with low-power lasers nds a wide area of application in different sectors, especially for pain control, physiotherapy, and esthetics. The use of what is called low-level
laser therapy (LLLT) in wound care is currently much discussed.
In the laboratory, various studies report [10,
11] an activity of increasing cellular metabolic
capacities, with a consequent increase in proliferative capacities, and Besser [11] proposes
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Table 17.5 Results of some reviews from the literature
Authors/years Question mark Conclusions Flemming 1999
[17] Flemming 2000
[18] 2005 items [19] Mechanism and
Socorro da Silva Dias Andrade 2014 [20]
Beckmann 2014 [21]
Percival 2015 [22] Infection and
Saltiel Machado 2017 [23]
Venous ulcers Were not found any evidence of the benet of low-level laser therapy
per se on venous leg ulcer healing
Venous ulcers (Cochrane database)
efcacy
General evaluation When applied to skin wounds, is able to promote major physiological
Diabetic foot The available studies about LLLT as treatment methods for diabetic
biolm
Pressure sores Signicant results were observed in the use of LLT with a 658nm
Were found no evidence of any benet associated with low-level laser therapy on venous leg ulcer healing
Future studies should be well-controlled investigations with rational selection of lasers and treatment parameters. In the absence of such studies, the literature does not appear to support widespread use of LLLT in wound healing at this time
effects, such as anti- inammatory resolution, neoangiogenesis, epithelial and broblast proliferation, collagen synthesis and deposition, revascularization, and wound contraction
ulcers give positive results and encourage further investigations. In order to obtain conclusive evidence of low-level laser in treating diabetic foot ulcers
Efforts must be addressed to standardize phototherapy procedures as well as to develop suitable invitro and invivo biolm models to test LLLT efcacy in promoting biolm eradication and wound healing
wavelength, and no evidence was found for the use of wavelengths above that for the treatment of PU
E. Ricci
its use for the prevention of infections in chronic lesions. In studies on animal models, Rodrigo [12] and Posten [13] report an efcacy of LLLT and Do Nascimento [14] links its effectiveness by stating that “it is more effective combining higher intensity with short wavelength or lower intensity with higher wavelength.” Gong [15] reports a reduction in green light laser scarring, and Gupta [16] nds inammation control in a burn pattern on rats.
LLLT would therefore have a theoretical basis of high application, but applied studies on humans are contradictory. Table17.5 shows the results of some reviews found in the literature; As can be seen, there are some contradictions and, at the present time, it is not possible to draw conclu­sions that give indications of use or conclusive indications.
The same situation can be observed by analyz­ing the published studies, out of 11 RCTs detected in the literature [2434], only two report statistically signicant results, and Basavaraj [30] and Fonseca Santos [33] both studies on dia­betic foot, while Saltmarche [26] reports a favor­able trend for use. The other eight report no results.
In the end, currently well-established use of ablative lasers, especially CO2 that has been more studied both as a debrider and for the removal of biolm, has also shown a reduction in repair times. For LLLT, the main confounders remain the types of wavelength and the doses to be administered in addition to the time and fre­quency of application. This fact could explain the important difference between experimental work and clinical application. However, there is an increasing interest in additional treatments based on the criteria of physics and therefore there will probably be an increase in use and available stud­ies in the next years.
References
1. Maiman TH. Stimulated optical radiation in ruby. Nature. 1960;187:493–4.
2. Norme EN 60825–1 safety of laser products—part 1: equipment classication and requirements (IEC 60825–1:2007).
3. Hajhosseini B, Grace J, Chiou GJ, Dori G, Fukaya E, Venita Chandra V, Meyer S, Gurtner CG.Er:YAG laser vs. sharp debridement in management of chronic wounds: effects on pain and bacterial load. Wound Repair Regen. 2020;28(1):118–25.
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