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Background: Photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) is an important and useful intervention used for removing non-invasive bladder cancer (NMIBC). Several PDD devices can be used in clinical practice, but few reports have compared them.In this study, we examined the differences in detected fluorescence intensity for each PDD device., Methods: The PDD device was used from OLYMPUS, Richard Wolf, and Karl Storz. Light power and illuminance from endoscope were measured. For each PDD device, fluorescence intensity was measured at 3 cm and 8 cm distance from the protoporphyrin IX (PpIX) phantom to the cystoscope., Results: The variation of excitation light power with observation distance were 35.0 %, 27.0 %, and 28.2 % for OLYMPUS, Richard Wolf, and Karl Storz, respectively. The variation of fluorescence intensity with observation distance were 132.8 %, 120.5 %, and 49.8 % for OLYMPUS, Richard Wolf, and Karl Storz, respectively., Conclusions: PDD devices used in clinical practice show both some performance differences between the PDD systems themselves, and also differences in observed fluorescence intensity., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: This study aimed to evaluate the efficacy and safety of nanosecond laser treatment of pigmented lesions in silico using a model of melanosome disruption threshold fluence (MDTF) based on skin optical properties., Methods: Particle size analysis and scanning electron microscopy were performed to determine the threshold fluence for melanosome disruption using a nanosecond laser. By inputting the obtained threshold fluence into the MDTF model and considering the variability in skin optical properties, irradiation parameters were calculated and compared with the results from clinical studies., Results: The threshold fluences for 532 and 755 nm nanosecond laser irradiation were determined to be 3.0 and 15.0 J/cm 2 , respectively. In silico analysis showed that the incident fluence for moderately pigmented skin should be 1.2 times that for lightly pigmented skin, whereas it should be 50% lower than that for lightly pigmented skin to achieve the same level of energy deposition. Clinically applied fluences for moderately pigmented skin are at the low end of the calculated range of values, suggesting that the clinical fluence is chosen to minimize energy deposition in normal tissues., Conclusions: Our results showed that the MDTF model can be used to evaluate nanosecond laser treatments and provide clinical guidance on fluence settings based on laser-tissue interactions in moderately pigmented skin. The in silico method can, therefore, provide a robust and quantitative retrospective evaluation of the treatment effects that accounts for variation in irradiation parameters among patients by combining the MDTF model with the in vivo optical properties of individual skin types., (© 2024 Wiley Periodicals LLC.)

Significance: For therapeutic approaches for upper tract urothelial carcinomas, the absorption μ a and reduced scattering μ s ' coefficients of these tissues are essential parameters to quantitatively evaluate the distribution of light treatment effects., Aim: The μ a and μ s ' spectra of the human ureter, fatty tissue, ureteral and renal pelvic carcinomas, and porcine ureter and fatty tissue are measured over 400 to 700 nm to evaluate projected light penetration depths δ ., Approach: The optical properties were determined with a double integrating sphere optical system and inverse Monte Carlo methods. δ was calculated and compared between normal and cancerous human tissues as well as between normal human and porcine tissues., Results: μ a and μ s ' spectra of each tissue were determined. The δ of the normal human ureter was less than those of the ureteral and renal pelvic carcinomas, whereas that of the porcine ureter was similar to that of the human ureter over 400 to 600 nm and ∼ 0.2 times smaller above 600 nm., Conclusion: Optical properties of human and porcine upper urinary tracts provide insights into light distributions and the validity of ex vivo porcine models in preclinical evaluations of laser treatments., (© 2024 The Authors.)

Short-pulsed lasers can treat dermal pigmented lesions through selective photothermolysis. The irradiated light experiences multiple scattering by the skin and is absorbed by abnormal melanosomes as well as by normal blood vessels above the target. Because the fluence is extremely high, the absorbed light can cause thermal damage to the adjacent tissue components, leading to complications. To minimize radiant exposure and reduce the risk of burns, a model of the melanosome-disruption threshold fluence (MDTF) has been developed that accounts for the light-propagation efficiency in the skin. However, the light-propagation efficiency is attenuated because of multiple scattering, which limits the extent to which the radiant exposure required for treatment can be reduced. Here, this study demonstrates the principle of melanosome disruption with localized thermal damage through a turbid medium by ultralow radiant exposure of a short-pulsed laser. The MDTF model was combined with a wavefront-shaping technique to design an irradiation condition that can increase the light-propagation efficiency to the target. Under this irradiation condition, melanosomes were disrupted at a radiant exposure 25 times lower than the minimal value used in conventional laser treatments. Furthermore, almost no thermal damage to the skin was confirmed through a numerical simulation. These experimental and numerical results show the potential for noninvasive melanosome disruption and may lead to the improvement of the safety of short-pulsed laser treatment., (© 2024. The Author(s).)

Background and Objectives: A threshold fluence for melanosome disruption has the potential to provide a robust numerical indicator for establishing clinical endpoints for pigmented lesion treatment using a picosecond laser. Although the thresholds for a 755-nm picosecond laser were previously reported, the wavelength dependence has not been investigated. In this study, wavelength-dependent threshold fluences for melanosome disruption were determined. Using a mathematical model based on the thresholds, irradiation parameters for 532-, 730-, 755-, 785-, and 1064-nm picosecond laser treatments were evaluated quantitatively., Study Design/materials and Methods: A suspension of melanosomes extracted from porcine eyes was irradiated using picosecond lasers with varying fluence. The mean particle size of the irradiated melanosomes was measured by dynamic light scattering, and their disruption was observed by scanning electron microscopy to determine the disruption thresholds. A mathematical model was developed, combined with the threshold obtained and Monte Carlo light transport to calculate irradiation parameters required to disrupt melanosomes within the skin tissue., Results: The threshold fluences were determined to be 0.95, 2.25, 2.75, and 6.50 J/cm² for 532-, 730-, 785-, and 1064-nm picosecond lasers, respectively. The numerical results quantitatively revealed the relationship between irradiation wavelength, incident fluence, and spot size required to disrupt melanosomes distributed at different depths in the skin tissue. The calculated irradiation parameters were consistent with clinical parameters that showed high efficacy with a low incidence of complications., Conclusion: The wavelength-dependent thresholds for melanosome disruption were determined. The results of the evaluation of irradiation parameters from the threshold-based analysis provided numerical indicators for setting the clinical endpoints for 532-, 730-, 755-, 785-, and 1064-nm picosecond lasers., (© 2024 Wiley Periodicals LLC.)

Background: The increasing abundance of drug-resistant bacteria is a global threat. Photodynamic therapy is an entirely new, non-invasive method for treating infections caused by antibiotic-resistant strains. We previously described the bactericidal effect of photodynamic therapy on infections caused by a single type of bacterium. We showed that gram-positive and gram-negative bacteria could be killed with 5-aminolevulic acid and 410 nm light, respectively. However, clinically, mixed infections are common and difficult to treat., Objective: We investigated the bactericidal effects of photodynamic therapy on mixed infections of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa., Methods: We compared bacterial growth with and without photodynamic therapy in vitro. Then, in vivo, we studied mixed infections in a mouse skin ulcer model. We evaluated the rates of ulcer area reduction and transitions to healing in treated and untreated mice. In addition, a comparison was made between PDT and existing topical drugs., Results: We found that photodynamic therapy markedly reduced the growth of both methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, in culture, and it reduced the skin ulcer areas in mice. PDT was also more effective than existing topical medicines., Conclusion: This study showed that photodynamic therapy had antibacterial effects against a mixed infection of gram-positive and gram-negative bacteria, and it promoted skin ulcer healing. These results suggested that photodynamic therapy could be effective in both single- and mixed-bacterial infections., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This study presents a depth map estimation of fluorescent objects in turbid media, such as biological tissue based on fluorescence observation by two-wavelength excitation and deep learning-based processing. A U-Net-based convolutional neural network is adapted for fluorophore depth maps from the ratiometric information of the two-wavelength excitation fluorescence. The proposed method offers depth map estimation from wide-field fluorescence images with rapid processing. The feasibility of the proposed method was demonstrated experimentally by estimating the depth map of protoporphyrin IX, a recognized cancer biomarker, at different depths within an optical phantom., Competing Interests: The authors declare no conflicts of interest related to this article., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Laser ablation is a minimally invasive therapeutic technique to denature tumors through coagulation and/or vaporization. Computational simulations of laser ablation can evaluate treatment outcomes quantitatively and provide numerical indices to determine treatment conditions, thus accelerating the technique's clinical application. These simulations involve calculations of light transport, thermal diffusion, and the extent of thermal damage. The optical properties of tissue, which govern light transport through the tissue, vary during heating, and this affects the treatment outcomes. Nevertheless, the optical properties in conventional simulations of coagulation and vaporization remain constant. Here, we propose a laser ablation simulation based on Monte Carlo light transport with a dynamic optical properties (DOP) model. The proposed simulation is validated by performing optical properties measurements and laser irradiation experiments on porcine liver tissue. The DOP model showed the replicability of the changes in tissue optical properties during heating. Furthermore, the proposed simulation estimated coagulation areas that were comparable to experimental results at low-power irradiation settings and provided more than 2.5 times higher accuracy when calculating coagulation and vaporization areas than simulations using static optical properties at high-power irradiation settings. Our results demonstrate the proposed simulation's applicability to coagulation and vaporization region calculations in tissue for retrospectively evaluating the treatment effects of laser ablation., (© 2023. The Author(s).)

Background and Objectives: The clinical use of 532-nm short-pulsed lasers has provided effective treatment of epidermal pigmented lesions. However, the detection of significant differences in treatment effects between picosecond and nanosecond lasers has still varied among clinical studies. For robust evaluation of the differences based on the treatment mechanism, this study presents a nonlinear absorption-based analysis of energy deposition in melanosomes for 532-nm short-pulsed laser treatment., Study Design/materials and Methods: Nonlinear absorption by melanin is modeled based on sequential two-photon absorption. Absorption cross-sections and nonradiative lifetimes of melanin, which are necessary for the nonlinear absorption-based analysis, are determined from transmittance measurement. Using the model and parameters, energy deposition in melanosomes was calculated with varying fluence and pulse width settings, including actual clinical parameters., Results: The energy deposition in melanosomes increased with shorter laser pulses, and subnanosecond laser pulses were found to be most efficient. The comparison of energy deposition calculated using clinical parameters demonstrated the differences in treatment effects between picosecond and nanosecond lasers reported in clinical studies., Conclusion: The nonlinear absorption-based analysis provides quantitative evidence for the safety and efficacy evaluation of short-pulsed laser treatments, which may lead to the establishment of numerical indices for determining treatment conditions. Future studies considering the effects of the surrounding tissue on energy deposition in melanosomes will be needed., (© 2023 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.)

A miniaturized endoscopic laser system with laser steering has great potential to expand the application of minimally invasive laser treatment for micro-lesions inside narrow organs. The conventional systems require separate optical paths for endoscopic imaging and laser steering, which limits their application inside narrower organs. Herein, we present a novel endoscopic image-guided laser treatment system with a thin tip that can access inside narrow organs. The system uses a single fiber bundle to simultaneously acquire endoscopic images and modulate the laser-irradiated area. The insertion and operation of the system in a narrow space were demonstrated using an artificial vascular model. Repeated laser steering along set targets demonstrated accurate laser irradiation within a root-mean-square error of 28 [Formula: see text]m, and static repeatability such that the laser irradiation position was controlled within a 12 [Formula: see text]m radius of dispersion about the mean trajectory. Unexpected irradiation on the distal irradiated plane due to fiber bundle crosstalk was reduced by selecting the appropriate laser input diameter. The laser steering trajectory spatially controlled the photothermal effects, vaporization, and coagulation of chicken liver tissue. This novel system achieves minimally invasive endoscopic laser treatment with high lesion-selectivity in narrow organs, such as the peripheral lung and coronary arteries., (© 2023. The Author(s).)

Gabapentinoids are specific ligands for the α 2 δ-1 subunit of voltage-gated calcium channels. This class of drugs, including gabapentin and pregabalin, exert various pharmacological effects and are widely used for the treatment of epilepsy, anxiety, and chronic pain. The mechanism of action of gabapentinoids involves both direct modulation of calcium channel kinetics and inhibition of channel trafficking and expression, which contribute to the above pharmacological effects. In the present study, we investigated the effects of mirogabalin, a novel potent gabapentinoid, on expression levels of the α 2 δ-1 subunit in the spinal dorsal horn in a rat model of spinal nerve ligation (SNL) as an experimental animal model for peripheral neuropathic pain. The neuropathic pain state was induced by SNL in male Sprague - Dawley rats. After the development of mechanical hypersensitivity, the animals received 10 mg/kg mirogabalin or vehicle orally for 5 consecutive days and were subjected to immunohistochemical analysis of α 2 δ-1 subunit expression in the spinal cord. In the SNL model rats, expression of the α 2 δ-1 subunit significantly increased in the spinal dorsal horn at the ipsilateral side of nerve injury, while mirogabalin inhibited this increase. In conclusion, the α 2 δ-1 subunit was upregulated in the spinal dorsal horn of SNL model rats, and repeated administration of mirogabalin inhibited this upregulation. The inhibitory effect of mirogabalin on upregulation of the α 2 δ-1 subunit after nerve injury is considered to contribute to its analgesic effects in peripheral neuropathic pain., Competing Interests: YD, NK, KK, and YK are employees of Daiichi Sankyo Co., Ltd., and HU, YS, KI, and YO are employees of Daiichi Sankyo RD Novare Co., Ltd. This work was sponsored by Daiichi Sankyo Co., Ltd., (Thieme. All rights reserved.)

Background: Antimicrobial photodynamic therapy (aPDT) using aminolaevulinic acid (ALA) is a promising alternative to antibiotic therapy. ALA administration induces protoporphyrin IX (PpIX) accumulation in bacteria, and light excitation of the accumulated PpIX generates singlet oxygen to bacterial toxicity. Several factors, including drug administration and light irradiation conditions, contribute to the antibiotic effect. Such multiple parameters should be determined moderately for effective aPDT in clinical practice., Methods: A mathematical model to predict bacterial dynamics in ALA-aPDT following clinical conditions was constructed. Applying a pharmacokineticspharmacodynamics (PK-PD) approach, which is widely used in antimicrobial drug evaluation, viable bacteria count by defining the bactericidal rate as the concentration of singlet oxygen produced when PpIX in bacteria is irradiated by light., Results: The in vitro experimental results of ALA-aPDT for Pseudomonas aeruginosa demonstrated the PK-PD model validity. The killing rate has an upper limit, and the lower power density for a long irradiation time can suppress the viable bacteria number when the light dosages are the same., Conclusions: This study proposed a model of bacterial viability change in ALA-aPDT based on the PK-PD model and confirmed, by in vitro experiments using PA, that the variation of bacterial viability with light-sensitive substance concentration and light irradiation power densities could be expressed. Further validation of the PK-PD model with other gram negative and gram positive strains will be needed., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Objectives: In this study, the threshold fluences for disrupting the melanosomes for pigmented skin lesion treatment were determined using a 755-nm picosecond laser for clinical use. Based on the melanosome disruption thresholds, incident fluences corresponding to the target lesion depths were evaluated in silico for different laser spot sizes., Study Design/materials and Methods: Melanosome samples were isolated from porcine eyes as alternative samples for human cutaneous melanosomes. The isolated melanosomes were exposed to 755-nm picosecond laser pulses to measure the mean particle sizes by dynamic light scattering and confirm their disruption by scanning electron microscopy. The threshold fluences were statistically determined from the relationships between the irradiated fluences and the mean particle sizes. Incident fluences of picosecond laser pulses for the disruption of melanosomes located at different depths in skin tissue were calculated through a light transport simulation using the obtained thresholds., Results: The threshold fluences of 550- and 750-picosecond laser pulses were determined to be 2.19 and 2.49 J/cm 2 , respectively. The numerical simulation indicated that appropriate incident fluences of picosecond laser pulses differ depending on the depth distribution of the melanosomes in the skin tissue, and large spot sizes are desirable for disrupting the melanosomes more deeply located within the skin tissue., Conclusion: The threshold fluences of picosecond laser pulses for melanosome disruption were determined. The incident fluence analysis based on the thresholds for melanosome disruption provides valuable information for the selection of irradiation endpoints for picosecond laser treatment of pigmented skin lesions. Lasers Surg. Med. © 2021 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC., (© 2021 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.)

Background: A hybrid emergency room (ER) is defined as an emergency unit with four functions-performing resuscitation, computed tomography (CT), surgery, and angiography. However, the safety and efficacy of performing CT in a hybrid ER are unclear in primary surveys. Therefore, this study aimed to evaluate the safety and clinical effects of hybrid ERs., Methods: This retrospective observational study used data from the Shimane University Hospital Trauma Database from January 2016 to February 2019. Hospitalized patients with severe trauma and an injury severity score of ≥ 16 were divided into the non-hybrid ER group (n = 134) and the hybrid ER group (n = 145). The time from arrival to CT and interventions and the number of in-hospital survivors, preventable trauma deaths (PTD), and unexpected survivors (US) were assessed in both groups. Further, the amount of blood transfused was compared between the groups using propensity score matching., Results: The time from arrival to CT and interventions was significantly reduced in the hybrid ER group compared to that in the non-hybrid ER group (25 vs. 6 min; p < 0.0001 and 101 vs. 41 min; p = 0.0007, respectively). There was no significant difference in the rate of in-hospital survivors (96.9% vs. 96.3%; p = 0.770), PTD (0% vs. 0%), and US (9.0 vs. 6.2%; p = 0.497) between the groups. The amount of blood transfused was significantly lower in the hybrid ER group than in the non-hybrid ER group (whole blood 14 vs. 8, p = 0.004; red blood cell 6 vs. 2, p = 0.012; fresh frozen plasma 9 vs. 6, p = 0.021). This difference was maintained after propensity score matching (whole blood 28 [10-54] vs. 6 [4-16.5], p = 0.015; RBC 8 [2.75-26.5] vs. 2 [0-8.5], p = 0.020, 18 [5.5-27] vs. 6 [3.5-7.5], p = 0.057)., Conclusions: The study results suggest that trauma treatment in a hybrid ER is as safe as conventional treatment performed in a non-hybrid ER. Further, hybrid ERs, which can reduce the time for trauma surveys and treatment, do not require patient transfer and can reduce the amount of blood transfused during resuscitation.

The errata correct errors that appeared in Table 2 of the published article.

Background and Objectives: Computational clinical trial (CCT) in the field of laser medicine promotes clinical application of novel laser devices, because this trial carried out based on numerical modeling of laser-tissue interactions and simulation of a series of treatment process. To confirm the feasibility of the computational clinical trial of skin treatment with a novel picosecond laser, this paper presents an evaluation method of the safety., Study Design/materials and Methods: In this method, the light propagation and thermal diffusion process after ultrashort light pulse irradiation to a numerical skin model is calculated and the safety based on the photothermal damage is evaluated by computational modeling and simulation. As an example, the safety of a novel picosecond laser device was examined by comparing with several laser devices approved for clinical use., Results: The ratio of the maximum thermal damage induced by picosecond laser irradiation was 1.2 × 10 -2 % at the epidermis, while that caused by approved laser irradiation was 99 % at the capillary vessels. The numerical simulation demonstrated that less thermal damage was observed compared with the approved devices. The results show the safety simulated by photothermal damage calculation was consistent with the reported clinical trials., Conclusions: This computational clinical trial shows the feasibility of applying computational clinical trials for the safety evaluation of novel medical laser devices. In contrast to preclinical and clinical tests, the proposed computational method offers regulatory science for appropriately and quickly predicting and evaluating the safety of a novel laser device., (2020, Japan Medical Laser Laboratory.)