Long-Term Outcome of Photobiomodulation Therapy for Refractory Diabetic Wound After Secretory Carcinoma of the Parotid Gland Surgery: A Case Report.

Objective: To evaluate the efficacy and safety of photobiomodulation therapy (PBMT) in the treatment of diabetic patients with refractory wound. Background: Refractory wound is one of the most challenging clinical complications of diabetes mellitus. Studies have shown that PBMT can promote wound healing in many ways. Methods: We reported a 55-year-old male patient with refractory diabetic wound after secretory carcinoma of the parotid gland surgery responding to 810 nm laser. Results: After PBMT, the refractory diabetic wound healed gradually without adverse events. During follow-up 5-years, the healed wound remained stable and showed no signs of recurrence. Conclusions: PBMT can be potentially considered as a therapeutic method in diabetic patients with refractory diabetic wound.

Impact of Diabetes Mellitus on Head and Neck Cancer Patients Undergoing Concurrent Chemoradiotherapy.

In this retrospective study, we investigated the impact of diabetes mellitus (DM) on patients with head and neck cancer (HNC) undergoing concurrent chemoradiotherapy (CCRT). We analyzed the demographic and clinical characteristics, treatment tolerance, and toxicities of patients with HNC undergoing primary or adjuvant CCRT with or without DM between 2007 and 2016. Of the 556 patients undergoing CCRT, 84 (15.1%) had DM. Compared with patients without DM, patients with DM were significantly older (56.2 ± 11.2 vs. 51.9 ± 9.5 years, P < 0.001), received lower doses of cisplatin (adjuvant CCRT: 175.30 ± 84.03 vs. 214.88 ± 68.25, P = 0.014; primary CCRT: 142.84 ± 79.49 vs. 187.83 ± 76.19, P < 0.001), and experienced higher rates of infection (adjuvant CCRT: 52% vs. 30.5%, P = 0.042; primary CCRT: 45.8% vs. 22.9%, P < 0.001). Among patients undergoing primary CCRT, compared with those without DM, the patients with DM experienced significantly higher rates of hematologic toxicity (65.7% vs. 39.3%, P = 0.004) and treatment-related deaths (10.2% vs. 3.5%, P = 0.051); and a greater weight loss (-6.17 ± 9.27% vs. -4.49 ± 6.84, P = 0.078). Patients with HNC and DM undergoing CCRT, compared with patients without DM, experienced higher rates of infection and hematotoxicity, loss of body weight, and higher treatment-related mortality.

Role of the PI3K/AKT (mTOR and GSK3ß) signalling pathway and photobiomodulation in diabetic wound healing.

Activated phosphatidylinositol 3 kinase/Protein kinase B (PI3K/AKT) signalling with increased or reduced mTOR and GSK3ß activity influences the wound repair process. Diabetic wounds, usually ulcerated, are characterised by reduced growth factors and cellular performance. The occurrence of diabetic ulcers is linked to peripheral arterial disease, neuropathy, and wound contamination. Lasers or light emitting diodes (LEDs) provide photon energy with therapeutic benefits (Photobiomodulation-PBM), and has been broadly commended to quicken diabetic wound healing. PBM is efficient in the visible red and near-infrared electromagnetic spectrum, and fluencies ranging from 2 to 6 J/cm2. However, cellular and molecular mechanisms induced by PBM are not fully understood. In this review we discuss PBM and the PI3K/AKT pathway with specific focus on the mTOR and GSK3ß downstream activity in diabetic wound healing.

Long-term management and postmortem examination in a diabetic cat with acromegaly treated with two courses of radiation therapy.

A 12-year-old, castrated male cat with diabetes mellitus was diagnosed with acromegaly and examined with magnetic resonance imaging (enlarged pituitary gland, 8 mm); serum hormone concentrations were measured. After the first course of radiation therapy (4 Gy, 12 fractions), insulin administration was not required from day 420 after diagnosis. Enlarged pituitary tumor (8 mm) recurred, and insulin dosage amount of the cat was increased on day 1,065. The second course of radiation therapy (6 Gy, 4 fractions) was performed on day 1,201 and insulin administration was again discontinued. However, the cat died from lymphoma on day 1,397. Postmortem examination revealed pituitary adenoma. Most tumor cells were positive for chromogranin A, synaptophysin, and growth hormone immunohistochemistry. The pancreatic islet cells revealed diffuse hyperplasia. We achieved long-term successful management of an acromegalic cat with two courses of RT. However, a protocol for a second course of RT for feline recurrent pituitary tumor should be further discussed.

Phototherapy with LED Shows Promising Results in Healing Chronic Wounds in Diabetes Mellitus Patients: A Prospective Randomized Double-Blind Study.

OBJECTIVE: The study examined the influence of phototherapy with light-emitting diodes (LEDs) on chronic diabetic wound healing. BACKGROUND: Chronic diabetic wounds are very difficult to treat due to underlying conditions such as angiopathy and neuropathy, resulting in slow healing rates. Conventional treatment options are often insufficient and do not provide satisfactory outcomes. Phototherapy with LED enhances the healing processes through mechanisms of energy exchange between incoming photons and their target, the main one being cytochrome-c oxidase in mitochondria. METHODS: A double-blind, randomized study included 60 patients with a chronic diabetic wound treated at the University Medical Center Ljubljana between October 1, 2012 and December 1, 2014. Patients were randomized into either an active group (LED group) or a control group (Co-group). The active group was treated with LED 2.4 J/cm2 (wavelengths 625, 660, 850 nm) three times a week for 8 weeks. The Co-group was treated with light that simulated LED. Healing was evaluated using the Falanga wound bed score and wound surface area. RESULTS: The average baseline wound surface before treatment was 1315 mm2 in the LED group and 1584 mm2 in the Co-group (p = 0.80). After 8 weeks, the mean surface in the LED group was 56% of the baseline surface and 65% in the Co-group (p > 0.05). Falanga score evaluation showed significantly faster wound bed healing in the LED group compared with the Co-group (p < 0.05). CONCLUSIONS: According to our results, LED significantly improves healing of chronic diabetic wounds and prepares the wound bed for further coverage options.

Effect of 660 nm visible red light on cell proliferation and viability in diabetic models in vitro under stressed conditions.

The current study evaluated the photobiomodulatory effect of visible red light on cell proliferation and viability in various fibroblast diabetic models in vitro, namely, unstressed normal (N) and stressed normal wounded (NW), diabetic wounded (DW), hypoxic wounded (HW) and diabetic hypoxic wounded (DHW). Cells were irradiated at a wavelength of 660 nm with a fluence of 5 J/cm2 (11.23 mW/cm2), which related to an irradiation time of 7 min and 25 s. Control cells were not irradiated (0 J/cm2). Cells were incubated for 48 h and cellular proliferation was determined by measuring 5-bromo-2'-deoxyuridine (BrdU) in the S-phase (flow cytometry), while viability was assessed by the Trypan blue exclusion test and Apoptox-glo triplex assay. In comparison with the respective controls, PBM increased viability in N- (P ≤ 0.001), HW- (P ≤ 0.01) and DHW-cells (P ≤ 0.05). HW-cells showed a significant progression in the S-phase (P ≤ 0.05). Also, there was a decrease in the G2M phase in HW- and DHW-cells (P ≤ 0.05 and P ≤ 0.05, respectively). This study concludes that hypoxic wounded and diabetic hypoxic wounded models responded positively to PBM, and PBM does not damage stressed cells but has a stimulatory effect on cell viability and proliferation to promote repair and wound healing. This suggests that the more stressed the cells are the better they responded to photobiomodulation (PBM).

Anti-apoptotic and antioxidant effects of low dose gamma irradiation against diabetes-induced brain injury in rats.

The current study aimed to investigate the effect of different low doses of gamma irradiation on hyperglycemia-induced brain injury. The aim was further extended to investigate the sub-chronic effect of low dose radiation on the neuronal damage induced by diabetes. To induce diabetes, male albino rats were injected with dexamethasone (10 mg/kg/day, for 9 successive days, subcutaneously). Different diabetic groups were irradiated with 0.1, 0.25 and 0.5 Gy. The effect of low dose gamma irradiation on the hyperglycemia-induced brain damage based was analyzed at two levels: oxidative stress and apoptosis. The brain contents of glutathione, malondialdhyde and total nitrate/nitrite were measured to assess the oxidative stress. In order to evaluate the extent of the apoptotic changes in brain, tissue caspase-3 expression was detected using immunohistochemistry and the degree of DNA fragmentation was estimated. Moreover, brain tissues were examined using light microscopy to evaluate the histological changes in different groups and serum lactate dehydrogenase activity was determined as an indicator for the brain tissue damage. Results indicated that exposure to 0.5 Gy ameliorated the hyperglycemia and subsequently inhibited oxidative stress and apoptosis. Radiation exposure at this dose level also increased the survival rate of diabetic animals.

High incidence of ischemic stroke occurrence in irradiated lung cancer patients: a population-based surgical cohort study.

BACKGROUND AND PURPOSE: A high risk of stroke occurrence has been reported in several types of irradiated cancer patients. However, clinical data are lacking in irradiated lung cancer patients. The present study intended to explore a risk level of ischemic stroke occurrence in irradiated lung cancer patients. METHODS: A nationwide population-based database obtained from the Taiwan National Health Insurance was analyzed. Between 2003 and 2006, we recruited 560 resected lung cancer patients into two study groups: surgery-plus-irradiation (n = 112) and surgery-alone (n = 448). Patients treated with chemotherapy were excluded. Propensity score match was used for pairing cases with a ratio of 1∶4. Two-year ischemic-stroke-free survival was defined as the primary endpoint. RESULTS: Three observations supported a high risk of ischemic stroke occurrence in patients with postoperative irradiation when compared with those patients with surgery alone: first, a high incidence per 1,000 person-year (22.3 versus 11.2, 1.99 folds); second, a low two-year ischemic-stroke-free survival rate (92.2% versus 98.1%, P = 0.019); and third, a high adjusted hazard ratio (HR, 4.19; 95% CI, 1.44-12.22; P = 0.009). More notably, the highest risk of ischemic stroke occurrence was found in irradiated patients who had diabetes mellitus (HR, 34.74; 95% CI, 6.35->100; P<0.0001). CONCLUSIONS: A high incidence of ischemic stroke was observed in irradiated lung cancer patients, especially in those with diabetes mellitus. For these patients, close clinical surveillance and strict diabetes control should be considered. Further studies to define detail biological mechanisms are encouraged.

The effects of low-level laser irradiation on cellular viability and proliferation of human skin fibroblasts cultured in high glucose mediums.

Delayed wound healing is one of the most challenging complications of diabetes mellitus (DM) in clinical medicine. This study has aimed to evaluate the effects of low-level laser therapy (LLLT) on human skin fibroblasts (HSFs) cultured in a high glucose concentration. HSFs were cultured either in a concentration of physiologic glucose (5.5 mM/l) or high glucose media (11.1 and 15 mM/l) for either 1 or 2 weeks after which they were subsequently cultured in either the physiologic glucose or high concentration glucose media during laser irradiation. LLLT was carried out with a helium-neon (He-Ne) laser unit at energy densities of 0.5, 1, and 2 J/cm(2), and power density of 0.66 mW/cm(2) on 3 consecutive days. HSFs' viability and proliferation rate were evaluated with the dimethylthiazol-diphenyltetrazolium bromide (MTT) assay. The LLLT at densities of 0.5 and 1 J/cm(2) had stimulatory effects on the viability and proliferation rate of HSFs cultured in physiologic glucose (5.5 mM/l) medium compared to their control cultures (p = 0.002 and p = 0.046, respectively). All three doses of 0.5, 1, and 2 J/cm(2) had stimulatory effects on the proliferation rate of HSFs cultured in high glucose concentrations when compared to their control cultures (p = 0.042, p = 0.000, and p = 0.000, respectively). This study showed that HSFs originally cultured for 2 weeks in high glucose concentration followed by culture in physiologic glucose during laser irradiation showed enhanced cell viability and proliferation. Thus, LLLT had a stimulatory effect on these HSFs.

Effect of laser therapy on skeletal muscle repair process in diabetic rats.

Skeletal muscle myopathy is a common source of disability in diabetic patients. This study evaluated whether low-level laser therapy (LLLT) influences the healing morphology of injured skeletal muscle. Sixty-five male Wistar rats were divided as follows: (1) sham; (2) control; (3) diabetic; (4) diabetic sham; (5) nondiabetic cryoinjured submitted to LLLT (LLLT); (6) diabetic cryoinjured submitted to LLLT (D-LLLT); and (7) diabetic cryoinjured non-treated (D). Diabetes was induced with streptozotocin. Anterior tibialis muscle was cryoinjured and received LLLT daily (780 nm, 5 J/cm(2), 10 s per point; 0.2 J; total treatment, 1.6 J). Euthanasia occurred on day 1 in groups 1, 2, 3, and 4 and on days 1, 7, and 14 in groups 5, 6, and 7. Muscle samples were processed for H&E and Picrosirius Red and photographed. Leukocytes, myonecrosis, fibrosis, and immature fibers were manually quantified using the ImageJ software. On day 1, all cryoinjured groups were in the inflammatory phase. The D group exhibited more myonecrosis than LLLT group (p < 0.05). On day 14, the LLLT group was in the remodeling phase; the D group was still in the proliferative phase, with fibrosis, chronic inflammation, and granulation tissue; and the D-LLLT group was in an intermediary state in relation to the two previous groups. Under polarized light, on day 14, the LLLT and D-LLLT groups had organized collagen bundles in the perimysium, whereas the diabetic groups exhibited fibrosis. LLLT can have a positive effect on the morphology of skeletal muscle during the tissue repair process by enhancing the reorganization of myofibers and the perimysium, reducing fibrosis.

A histological evaluation of a low-level laser therapy as an adjunct to periodontal therapy in patients with diabetes mellitus.

Diabetes mellitus (DM) and chronic periodontitis are common chronic diseases in adults in the world population. DM has a strong influence on the oral cavity and represents a risk factor for gingivitis and periodontitis. Low-level laser therapy (LLLT) has proven effective in the reduction of inflammation and swelling. The aim of the present study was to evaluate the efficacy of LLLT in diabetic periodontitis through histological analysis. A total of 300 diabetics with chronic periodontal disease and teeth indicated for extraction were assigned into six equal groups. In the groups 1 and 4, indicated teeth were extracted before treatment, and in the rest of the groups upon completion of the entire treatment. All patients received oral hygiene instructions and full-mouth conservative periodontal treatment. In groups 3 and 6, LLLT was applied (670 nm, 5 mW, 2 J/cm(2), 16 min, 5 days). Histologic findings of gingival tissue treated with LLLT showed expressed healing, as is evident by the absence of inflammatory cells. Tissue edema could not be seen, and the number of blood vessels was reduced. In the gingival lamina, propria pronounced collagenization and homogenization were present. It can be concluded that LLLT has shown efficacy in the treatment of periodontitis in diabetics. Because of more pronounced alterations of periodontium in diabetics, the use of LLLT is of particular importance.

Low-level lasers as an adjunct in periodontal therapy in patients with diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) increases the risk of periodontitis, and severe periodontitis often coexists with severe DM. The proposed dual pathway of tissue destruction suggests that control of chronic periodontal infection and gingival inflammation is essential for achieving long-term control of DM. The purpose this study is to evaluate the effects of low-level laser therapy (LLLT) by exfoliative cytology in patients with DM and gingival inflammation. SUBJECTS AND METHODS: Three hundred patients were divided in three equal groups: Group 1 consisted of patients with periodontitis and type 1 DM, Group 2 of patients with periodontitis and type 2 DM, and Group 3 of patients with periodontitis (control group). After oral examination, smears were taken from gingival tissue, and afterward all of the patients received oral hygiene instructions, removal of dental plaque, and full-mouth scaling and root planing. A split-mouth design was applied; on the right side of jaws GaAlAs LLLT (670 nm, 5 mW, 14 min/day) (model Mils 94; Optica Laser, Sofia, Bulgaria) was applied for five consecutive days. After the therapy was completed, smears from both sides of jaws were taken. The morphometric analysis was done using the National Institutes of Health Image software program and a model NU2 microscope (Carl Zeiss, Jena, Germany). RESULTS: Investigated parameters were significantly lower after therapy compared with values before therapy. After therapy on the side subjected to LLLT, there was no significantly difference between patients with DM and the control group. CONCLUSIONS: It can be concluded that LLLT as an adjunct in periodontal therapy reduces gingival inflammation in patients with DM and periodontitis.

[Low power laser efficacy in the therapy of inflamed gingive in diabetics with parodontopathy].

BACKGROUND/AIM: There is clear evidence on direct relationship between periodontal disease and diabetes mellitus. Many investigations point out greater prevalence and severity of periodontal disease among diabetic patients. During last decade, low level laser therapy has been used in periodontal therapy. It has biostimulative effect, accelerates wound healing, minimizes pain and swelling, and there is almost no contraindication for its usage. The aim of the paper was to investigate the efficiency of low level laser therapy as adjuvant tool in reduction of gingival inflammation in diabetic patients. METHODS: The study incuded 150 participants divided into three groups: group I (50 participants with diabetes mellitus type 1 and periodontal disease), group II (50 participants with diabetes mellitus type 2 and periodontal disease), group III (nondiabetic participants with periodontal disease). Gingival health evaluation was done using gingival index Löe-Silness. Soft and hard deposits were removed, periodontal pockets cleaned and GaA1As low level laser therapy (5 mW) applied five consecutive days. In each patient, low level laser therapy was not applied on the left side of the jaw in order to compare the effects of the applied therapy. After the first, third and fifth therapy and one month after the last visit gingival index was evaluated. Before the first and after the fifth therapy exfoliative cytology of gingiva was done and nuclei areal was analyzed morphometrically. RESULTS: After all investigated periods, gingival index and nuclei areal were significantly decreased comparing to values before the therapy, at both jaw sides (p < 0.001). After the 1st, 3rd and 5th therapy, the t-test showed a significantly decreased gingival index at the lased side of jaw comparing to non-lased side. CONCLUSION: Low level laser therapy is efficient in gingival inflammation elimination and can be proposed as an adjuvant tool in basic periodontal therapy of diabetic patients.

[Low-level laser therapy in the treatment of diabetic ulcers: an evidence problem]. / Laserterapia de baixa potência no tratamento de úlceras diabéticas: um problema de evidência.

INTRODUCTION: Diabetes Mellitus is the leading cause of lower limb amputation, representing a significant economic cost for health services. The development of diabetic ulcers is a main risk factor for amputations, which have a high mortality rate at five years. The ischemia caused by macrovascular disease is a key pathophysiological factor in the development of ischemic ulcers. Existing treatments are prolonged and associated with high rates of failure and relapse, requiring the combination of multiple therapeutic modalities. Lowlevel laser therapy has been used as an adjuvant therapy for diabetic foot ulcers, since the 1960's, due to its hypothetical stimulating effects over microcirculation and tissue repair. MATERIAL AND METHODS: Identification of published scientific studies through a literature search on PubMed, The Cochrane Library and Cochrane Controlled Trials Register. DISCUSSION AND CONCLUSIONS: Existing evidence is favourable for in vitro cell models, but conflicting in animal models and human populations. There is significant methodological heterogeneity, which may be responsible for discordant results. Guidelines are proposed for future studies in this area, including the detailed characterization of ulcers and the parameters of laser treatment. Well-controlled studies, randomized and double-blind are needed. Accordingly to the primum non nocere, laser therapy can and should be used as adjunctive therapy in the treatment of diabetic foot, because it isn't invasive, has low costs and is a fast therapy without significant adverse effects.

Comparative analysis of coherent light action (laser) versus non-coherent light (light-emitting diode) for tissue repair in diabetic rats.

The already known benefits produced by the interaction of coherent light (laser) with biologic tissues determine its use as an adjuvant in the treatment of several complications associated with diabetes. Non-coherent light, such as that emitted by light emitting diodes (LEDs), becomes a promising alternative, because of its low cost and easy handling in these applications. Thirty-six rats were given surgical dorsum lesions. The lesions for the control group did not receive any supporting therapy. The other groups were irradiated only once, 30 min after the establishment of the lesion, with LED (640 nm with 40 nm full bandwidth at half maximum) or laser (660 nm). The histomorphological and histomorphometrical parameters were quantified. The coherent and non-coherent lights produced similar effects during a period of 168 h after the lesions had been made. For the group composed of diabetic animals, 72 h after creation of the lesion, it was observed that the therapy with LEDs had been more efficient than that with the laser in the reduction of the wounds' diameters.

Pulsed electromagnetic fields accelerate normal and diabetic wound healing by increasing endogenous FGF-2 release.

BACKGROUND: Chronic wounds, particularly in diabetics, result in significant morbidity and mortality and have a profound economic impact. The authors demonstrate that pulsed electromagnetic fields significantly improve both diabetic and normal wound healing in 66 mice through up-regulation of fibroblast growth factor (FGF)-2 and are able to prevent tissue necrosis in diabetic tissue after an ischemic insult. METHODS: Db/db and C57BL6 mice were wounded and exposed to pulsed electromagnetic fields. Gross closure, cell proliferation, and vascularity were assessed. Cultured medium from human umbilical vein endothelial cells exposed to pulsed electromagnetic fields was analyzed for FGF-2 and applied topically to wounds. Skin flaps were created on streptozocin-induced diabetic mice and exposed to pulsed electromagnetic fields. Percentage necrosis, oxygen tension, and vascularity were determined. RESULTS: Pulsed electromagnetic fields accelerated wound closure in diabetic and normal mice. Cell proliferation and CD31 density were significantly increased in pulsed electromagnetic field-treated groups. Cultured medium from human umbilical vein endothelial cells in pulsed electromagnetic fields exhibited a three-fold increase in FGF-2, which facilitated healing when applied to wounds. Skin on diabetic mice exposed to pulsed electromagnetic fields did not exhibit tissue necrosis and demonstrated oxygen tensions and vascularity comparable to those in normal animals. CONCLUSIONS: This study demonstrates that pulsed electromagnetic fields are able to accelerate wound healing under diabetic and normal conditions by up-regulation of FGF-2-mediated angiogenesis. They also prevented tissue necrosis in response to a standardized ischemic insult, suggesting that noninvasive angiogenic stimulation by pulsed electromagnetic fields may be useful to prevent ulcer formation, necrosis, and amputation in diabetic patients.

Effects of endogenous cyclotronic ionic resonance (ICR) on macular diabetic edema: preliminary results.

The intent in this research was to verify the effects of the application of low frequency magnetic fields to cases of macular diabetic edema. We treated six patients afflicted by non-proliferating diabetic retinopathy with macular oedema. Quantitative clinical appraisals of the retinal thickness were obtained for the Optical Coherence Tomography (OCT I). None of the cases affected by non-cystoid macular oedema (non-CMO), or with a relevant ischemic component, evidenced by retinal fluorangiography, had further worsening in their clinical course during the treatment. Only one of the patients, who underwent a long treatment period with ICR demonstrated a significant reduction of the macular edema, with no need of other invasive therapeutic procedures (intravitreous injection of triamcinolone and/or laser therapy).

Effect of low-level laser therapy on skin fibroblasts of streptozotocin-diabetic rats.

OBJECTIVE: This study explored the effects of low-level laser therapy (LLLT) on cellular changes in cell culture and organ culture of skin from streptozotocin-diabetic (STZ-D) rats. BACKGROUND DATA: Growth of skin and its fibroblasts are impaired in diabetes. Therefore the healing of skin wounds is impaired in diabetic patients. The positive effects of LLLT on complications of diabetes in patients and animal models have been shown. METHODS: Diabetes was induced in rats by streptozotocin 30 days after its injection. Two sets of skin samples were extracted from skin under sterile conditions. Fibroblasts that were extruded from the samples were proliferated in vitro, and another set of samples were cultured as organ culture. A 24-well culture medium containing Dulbecco's modified minimum essential medium was supplemented by 12% fetal bovine serum. There were five laser-treated and five sham-exposed groups. A helium-neon laser was used, and 0.9-4 J/cm(2) energy densities were applied four times to each organ culture and cell culture. The organ cultures were analyzed by light microscopy and transmission electron microscopy examinations. Cell proliferation was evaluated by dimethylthiazol-diphenyltetrazolium bromide (MTT) assay. RESULTS: Statistical analysis revealed that 4-J/cm(2) irradiation significantly increases the fibroblast numbers compared to the sham-exposed cultures (p = 0.046). CONCLUSION: It is concluded that LLLT resulted in a significant increase of fibroblast proliferation of STZ-D rats in vitro.

Two-year clinical follow-up of 90Sr/90 Y beta-radiation versus placebo control for the treatment of in-stent restenosis.

BACKGROUND: It is an ongoing concern that intracoronary brachytherapy may possibly just delay the problem of in-stent restenosis ("late catch up"). For gamma-radiation, 3 placebo-controlled studies have shown the maintenance of the initially positive effect after 2 years, but similar data do not exist for beta-radiation. STents And Restenosis Trial (START) was the first placebo-controlled randomized trial for in-stent restenosis with beta-radiation; herein, we report the 2-year clinical follow-up. METHODS AND RESULTS: Two hundred and forty-four patients were randomized to active treatment, 232 patients to placebo (nonactive source train) treatment. The primary end point of efficacy was target vessel revascularization (TVR); primary safety end point was any major adverse cardiac event (MACE) at 8 months and 2 years. Two-year clinical outcome in patients receiving brachytherapy was based on 195 of 244 original patients (79.9%) and in the placebo arm on 183 of 232 original patients (78.9%). TVR was significantly reduced by 25%; from 36.6% (placebo) to 27.5% (brachytherapy) remained significant after 2 years (RR .7 [.57-.98], 95% CI -9.2 [-17.5-0.8]). The Kaplan-Meier analysis for TVR and MACE showed improvement beginning approximately 90 days after radiation and remained almost constant for the 2 following years. Freedom from TVR was significantly increased from 62.4% +/- 3.8% to 71.6% +/- 3.3% (P = .027) and freedom from MACE from 58.9% +/- 3.7% to 68.0% +/- 3.4% (P = .035). CONCLUSIONS: The START trial shows for the first time that the initial beneficial effects of intracoronary brachytherapy with beta-radiation using 90 Sr/ 90 Y are maintained at 2-year clinical follow-up period.

Low level laser therapy (LLLT) as an effective therapeutic modality for delayed wound healing.

Low level laser therapy (LLLT) is a form of phototherapy that involves the application of low power monochromatic and coherent light to injuries and lesions. It has been used successfully to induce wound healing in nonhealing defects. Other wounds treated with lasers include burns, amputation injuries, skin grafts, infected wounds, and trapping injuries. The unique properties of lasers create an enormous potential for specific therapy of skin diseases. As with any new device, the most efficacious and appropriate use requires an understanding of the mechanisms of light interaction with tissue as well as the properties of the laser itself.