Efficacy of Er,Cr:YSGG Laser Application in Nonsurgical Treatment of Peri-implantitis: A Human Randomized Controlled Trial.

This investigation was designed to evaluate the efficacy of an erbium, chromium-doped yttrium, scandium, gallium and garnet (Er,Cr:YSGG) laser (laser group) compared to conventional mechanical debridement (control group) in the treatment of peri-implantitis. In a double-blinded, randomized, controlled clinical trial, 32 patients with 88 implants with peri-implantitis were randomly assigned to either group. Statistical analyses were performed at 9 months for both groups. The laser-treated group showed a statistically significant reduction in probing depth (PD) compared to the control group (P = .04), but no statistically significant differences were observed for clinical attachment level gain (P = .29) or reduction of bleeding on probing (P = .09). In the subgroup analysis, mandibular single implants with screw-retained restorations treated with Er,Cr:YSGG demonstrated a statistically significant decrease in PD (P < .05) compared to all other groups. A complete resolution of peri-implantitis was achieved in 21% of implants in the test group and 5% of implants in the control group. Er,Cr:YSGG laser is an efficacious therapeutic tool to treat peri-implantitis, achieving greater PD reduction than conventional mechanical debridement alone. Er,Cr:YSGG laser also showed increased benefits in the treatment of mandibular, screw-retained, and single-unit implants compared to the sole use of conventional mechanical debridement.

Dual-Responsive and ROS-Augmented Nanoplatform for Chemo/Photodynamic/Chemodynamic Combination Therapy of Triple Negative Breast Cancer.

Integrating chemodynamic therapy (CDT) and photodynamic therapy (PDT) into one nanoplatform can produce much more reactive oxygen species (ROS) for tumor therapy. Nevertheless, it is still a great challenge to selectively generate sufficient ROS in tumor regions. Meanwhile, CDT and PDT are restricted by insufficient H2O2 content in the tumor as well as by the limited tumor tissue penetration of the light source. In this study, a smart pH/ROS-responsive nanoplatform, Fe2+@UCM-BBD, is rationally designed for tumor combination therapy. The acidic microenvironment can induce the pH-responsive release of doxorubicin (DOX), which can induce tumor apoptosis through DNA damage. Beyond that, DOX can promote the production of H2O2, providing sufficient materials for CDT. Of note, upconversion nanoparticles at the core can convert the 980 nm light to red and green light, which are used to activate Ce6 to produce singlet oxygen (1O2) and achieve upconversion luminescence imaging, respectively. Then, the ROS-responsive linker bis-(alkylthio)alkene is cleaved by 1O2, resulting in the release of Fenton reagent (Fe2+) to realize CDT. Taken together, Fe2+@UCM-BBD exhibits on-demand therapeutic reagent release capability, excellent biocompatibility, and remarkable tumor inhibition ability via synergistic chemo/photodynamic/chemodynamic combination therapy.

Metabolic activity assessment by 18 F-fluorodeoxyglucose positron emission tomography in patients with hepatocellular carcinoma undergoing Yttrium-90 transarterial radioembolization.

BACKGROUND AND AIM: 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) is a functional image technique that can inform clinical decisions related to prognosis. We investigated the predictive role of 18 F-fluorodeoxyglucose PET/CT in patients with hepatocellular carcinoma (HCC) undergoing Yttrium-90 (Y-90) transarterial radioembolization (TARE). METHODS: Patients with HCC treated with TARE and pre-TARE PET/CT scan were recruited between 2009 and 2013. Maximum standardized uptake value and tumor-to-non-tumorous liver uptake ratio (TLR) were measured. Tumor response was evaluated in accordance with modified RECIST criteria at 3-month intervals after Y-90 TARE. RESULTS: Forty patients were included in the final analysis. The median age was 56.5 years and male predominant. Disease control in treated lesion was achieved in 82.5% (n = 33) of patients. During median 18.3-month follow-up, 27.5% (n = 11) of patients achieved progression-free survival. The cutoff of TLR, which was related to the median value, did not affect disease control rate, progression-free survival, and overall survival in patients with Y-90 TARE. CONCLUSIONS: The TLR-based stratification may be a simple method, but our study did not show the usefulness in predicting prognosis in HCC patients with Y-90 TARE. Further studies with large number of patients are needed.

A Janus upconverting nanoplatform with biodegradability for glutathione depletion, near-infrared light induced photodynamic therapy and accelerated excretion.

The major limitations of photodynamic therapy (PDT) are the poor tissue penetration of excitation light and the neutralization of reactive oxygen species (ROS) generated by overexpressed glutathione (GSH) in cancer cells. Despite tremendous efforts to design nanoplatforms, PDT still suffers from unsatisfactory effects. Furthermore, the residual of nanomaterials in the body has restricted their clinical application. To address these issues, Janus nanocomposites containing an Yb/Er codoped NaYF4 upconverting nanocrystal head and a disulfide-bridged mesoporous organosilicon body (UCN/MON) with loaded chlorin e6 (Ce6) were designed. On one hand, the upconverting nanocrystal head can convert near-infrared (NIR) light into visible light to activate Ce6 to release ROS. On the other hand, the silica body can be degraded though a redox reaction with GSH, to not only improve the tumor selectivity of the photosensitizer by redox- and pH-triggered Ce6 release, but also diminish the concentration of GSH in cancer cells to reduce the depletion of ROS. Thereby, an enhanced PDT triggered by NIR irradiation was achieved. Furthermore, UCN/MONs showed a higher clearance rate after therapeutic actions than nonbiodegradable UCN/MSNs due to their biocompatibility. Taken together, this work revealed the potential of UCN/MONs for highly efficient and NIR-induced PDT, highlighting the prospects of UCN/MONs in the clinic.

Activatable Photodynamic Therapy with Therapeutic Effect Prediction Based on a Self-correction Upconversion Nanoprobe.

Though emerging as a promising therapeutic approach for cancers, the crucial challenge for photodynamic therapy (PDT) is activatable phototoxicity for selective cancer cell destruction with low "off-target" damage and simultaneous therapeutic effect prediction. Here, we design an upconversion nanoprobe for intracellular cathepsin B (CaB)-responsive PDT with in situ self-corrected therapeutic effect prediction. The upconversion nanoprobe is composed of multishelled upconversion nanoparticles (UCNPs) NaYF4:Gd@NaYF4:Er,Yb@NaYF4:Nd,Yb, which covalently modified with an antenna molecule 800CW for UCNPs luminance enhancement under NIR irradiation, photosensitizer Rose Bengal (RB) for PDT, Cy3 for therapeutic effect prediction, and CaB substrate peptide labeled with a QSY7 quencher. The energy of UCNPs emission at 540 nm is transferred to Cy3/RB and eventually quenched by QSY7 via two continuous luminance resonance energy transfer processes from interior UCNPs to its surface-extended QSY7. The intracellular CaB specifically cleaves peptide to release QSY7, which correspondingly activates RB with reactive oxygen species (ROS) generation for PDT and recovers Cy3 luminance for CaB imaging. UCNPs emission at 540 nm remains unchanged during the peptide cleavage process, which is served as an internal standard for Cy3 luminance correction, and the fluorescence intensity ratio of Cy3 over UCNPs (FI583/FI540) is measured for self-corrected therapeutic effect prediction. The proposed self-corrected upconversion nanoprobe implies significant potential in precise tumor therapy.

Effect of 5α-reductase inhibitors on the efficiency of thulium:yttrium-aluminium-garnet (RevoLix®) vaporesection for treating benign prostatic hyperplasia.

Purpose: Preoperative use of 5α-reductase inhibitors (5ARIs) may cause fibrosis of the prostate tissue and reduce the efficiency of thulium laser surgery for treating benign prostate hyperplasia (BPH). Thus, we investigated the effects of preoperative 5ARI use in this setting. Materials and Methods: This retrospective study examined 184 patients who underwent thulium laser surgery for BPH during 2012-2017. Patients were grouped according to their 5ARI use in order to compare their preoperative and intraoperative characteristics and subsequent outcomes. Surgical efficiency was assessed using vaporesection efficiency. The total operation time, vaporesection time and prostate volume change were measured. Results: The 5ARI+ group included 83 patients (45.1%) and the 5ARI- group included 101 patients (54.9%). There were no significant differences in the two groups' preoperative characteristics, postoperative prostate size, thulium laser energy use, or prostate volume reduction rate. However, relative to the 5ARI- group, the 5ARI+ group had a significant shorter total operative time (65.0 min vs. 70.0 min, p=0.013) and a significantly shorter vaporesection time (48.0 min vs. 54.0 min, p=0.014), which resulted in significantly higher vaporesection efficiency in the 5ARI+ group (0.66 mL/min vs. 0.51 mL/min, p<0.001). Both groups exhibit significant improvements in their quality of life score and International Prostate Symptom Score during the 12-month follow-up. Conclusions: In contrast with our expectations, the preoperative use of 5ARI increased the efficiency of thulium laser surgery for BPH. Thus, it may not be necessary to stop 5ARI treatment before performing thulium laser surgery in this setting.

Long Term Follow-up of Intralesional Laser Photocoagulation for Head and Neck Lymphatic Malformations Using Neodymium-Yttrium-Aluminium-Garnet Laser.

BACKGROUND: Lymphatic malformations remain a challenge for patients and plastic surgeons. Promising results have been reported using intralesional laser photocoagulation (ILP) for treating vascular anomalies. BACKGROUND DATA: The objective of our study is to review the long-term results of a large series of lymphatic malformations in patients treated with ILP. MATERIALS AND METHODS: A retrospective review of 190 head and neck lymphatic malformations in patients were treated by ILP with an neodymium-yttrium-aluminum-garnet (Nd:YAG) laser (1064 nm) over a period of 20 years (January 1997-January 2016). Patients' ages ranged from 10 months to 12 years and 6 months (mean, 1 year and 11 months). The patient group consisted of 98 female and 92 male patients. RESULTS: Patients were treated with an Nd:YAG laser (Sharplan Inc, Allendale, New Jersey) delivered through a 600-µm optical fiber. Laser power was set at 7 to 15 W and delivered with a pulse duration of 7 to 15 seconds. All patients demonstrated improvement as judged by clinical assessment of the reduction in lesion size (range, 65%-100%; mean reduction, 85%). One hundred fifty-two (80%) patients had a more than 65% reduction of the volume in lymphatic malformations at 3 months after 1 treatment, and 171 (90%) patients had a more than 85% reduction of the volume after 2 treatments. Excellent results were seen in 19 (10%) patients after 3 treatments. Postoperative complications were related to photocoagulation that was delivered too extensively or superficially, with resultant ulceration, infection, induration, and scarring. CONCLUSIONS: Throughout the course of our long-term study, ILP using an Nd:YAG laser is an effective treatment modality for lymphatic malformations. Complications can be avoided if the potential for harm is kept in mind.

Comparison of the Neodymium-doped Yttrium Aluminum Garnet Capsulotomy Rate with Viscoimplantation and the Hydroimplantation Intraocular Lens Technique.

PURPOSE: To investigate the rate of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy in the hydroimplantation intraocular lens (IOL) technique. METHODS: This retrospective study was comprised of 6,192 eyes in 3,790 patients who underwent surgery from January 2013 to September 2017 and then were followed up for at least 1 year. The eyes of these patients were divided into two groups: either viscoimplantation or hydroimplantation. The follow-up examinations were carried out on the 1st day, 4th day, 1st month, and 3 months to 1 year postoperatively. The Nd:YAG capsulotomy rates were evaluated by the different IOL implantation techniques and IOL materials. RESULTS: The mean follow-up duration of the patients was in the viscoimplantation group 14.85 ± 2.43 and 15.05 ± 1.93 months in the hydroimplantation group. The Nd:YAG capsulotomy rate was significantly lower in the hydroimplantation group compared with the viscoimplantation group for the entire hydrophilic IOL model (p < 0.001). In addition, the Nd:YAG rate was lower in the hydroimplantation group that used a hydrophilic IOL than it was in the viscoimplantation group, which used a hydrophobic IOL. CONCLUSIONS: The hydroimplantation technique reduced the Nd:YAG capsulotomy rate.

Efficacy of using erbium, chromium-doped: Yttrium scandium gallium garnet laser-treated dentine in a dentine barrier test device.

OBJECTIVES: The aim of this study was to evaluate the efficacy of using erbium, chromium-doped:yttrium scandium gallium garnet (Er,Cr:YSGG) laser-treated dentine in a dentine barrier test device. MATERIALS AND METHODS: The test materials (G-Bond™ and Vitrebond™) were applied onto laser-treated or laser-untreated dentine discs. After 24 h of exposure with perfusion of the test chamber, cell survival was evaluated based on enzyme activity and compared to a nontoxic control material. The mean of the control was set to 100% viability. Data were analyzed using the one-way analysis of variance and the Tukey's honest significant difference tests. RESULTS: The responses of bovine pulp-derived cells after exposure to G-Bond and Vitrebond on Er,Cr:YSGG laser-treated and laser-untreated dentin were statistically different from negative control group (P < 0.05). CONCLUSION: Er,Cr:YSGG laser treatment was not successful enough in decreasing the cytotoxic effects of the dental materials. Different parameters of Er,Cr:YSGG laser or different laser types could be investigated as an alternative to minimizing the cytotoxic effects of dental materials.

Effect of laser peripheral iridotomy using argon and neodymium-YAG lasers on corneal endothelial cell density: 7-year longitudinal evaluation.

PURPOSE: To evaluate the changes in corneal endothelial cell density (ECD) over a 7-year period after laser peripheral iridotomy (LPI) using argon and neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers. STUDY DESIGN: Retrospective case series. METHODS: Eyes that underwent prophylactic LPI using argon and Nd:YAG lasers were followed up for 7 years. Central corneal endothelial cells were observed by use of noncontact specular microscopy preoperatively and at 1 and 7 years postoperatively. Changes in ECD and the associations between preoperative ECD and the total energy of the Nd:YAG laser were evaluated. RESULTS: Fifty-one eyes of 51 patients were followed up for 7 years. The ECD significantly decreased after LPI (P < 0.049), and the reduction rate at 1 year after the surgery (1.69 ± 4.80%, 95% CI: 0.34%-3.04%) was significantly higher than the annual reduction rates after 1 year (0.17 ± 0.85%/y, P = 0.036, 95% CI: -0.07% to 0.41%). No association was found between the preoperative ECD and the total laser energy. CONCLUSIONS: Long-term evaluation indicated that the reduction in ECD after argon-Nd:YAG laser LPI was present but small during the initial year and was negligible after 1 year.

Development of a functionalized UV-emitting nanocomposite for the treatment of cancer using indirect photodynamic therapy.

BACKGROUND: Photodynamic therapy is a promising cancer therapy modality but its application for deep-seated tumor is mainly hindered by the shallow penetration of visible light. X-ray-mediated photodynamic therapy (PDT) has gained a major attention owing to the limitless penetration of X-rays. However, substantial outcomes have still not been achieved due to the low luminescence efficiency of scintillating nanoparticles and weak energy transfer to the photosensitizer. The present work describes the development of Y2.99Pr0.01Al5O12-based (YP) mesoporous silica coated nanoparticles, multifunctionalized with protoporphyrin IX (PpIX) and folic acid (YPMS@PpIX@FA) for potential application in targeted deep PDT. RESULTS: A YP nanophosphor core was synthesized using the sol-gel method to be used as X-ray energy transducer and was then covered with a mesoporous silica layer. The luminescence analysis indicated a good spectral overlap between the PpIX and nanoscintillator at the Soret as well as Q-band region. The comparison of the emission spectra with or without PpIX showed signs of energy transfer, a prerequisite for deep PDT. In vitro studies showed the preferential uptake of the nanocomposite in cancer cells expressing the folate receptorFolr1, validating the targeting efficiency. Direct activation of conjugated PpIX with UVA in vitro induced ROS production causing breast and prostate cancer cell death indicating that the PpIX retained its activity after conjugation to the nanocomposite. The in vivo toxicity analysis showed the good biocompatibility and non-immunogenic response of YPMS@PpIX@FA. CONCLUSION: Our results indicate that YPMS@PpIX@FA nanocomposites are promising candidates for X-ray-mediated PDT of deep-seated tumors. The design of these nanoparticles allows the functionalization with exchangeable targeting ligands thus offering versatility, in order to target various cancer cells, expressing different molecular targets on their surface.

Targeted Yttrium 89-Doxorubicin Drug-Eluting Bead-A Safety and Feasibility Pilot Study in a Rabbit Liver Cancer Model.

The purpose of this article is to evaluate feasibility and safety of the cancer targeting (radio)-chemoembolization drug-eluting bead (TRCE-DEB) concept drug SW43-DOX-L-NETA(89Y) DEB for the intra-arterial treatment of VX2 rabbit liver tumors. The treatment compound comprises of the sigma-2 receptor ligand SW43 for cancer targeting, doxorubicin (DOX), and 89yttrium (89Y) as nonradioactive surrogate for therapeutic (yttrium-90, lutetium-177) and imaging (yttrium-86) radioisotopes via the chelator L-NETA. Ten New Zealand white rabbits with VX2 tumor allografts were used. SW43-DOX-89Y was synthesized, loaded onto DEB (100 µL; 100-300 µm), and administered intra-arterially in six rabbits at increasing doses (0.2-1.0 mg/kg). As controls, two rabbits each received either doxorubicin IV (0.3 mg/kg) or no treatment. Consecutive serum analysis for safety and histopathological evaluation after sacrifice were performed. One-Way ANOVA incl. Bonferroni Post-Hoc test was performed to compare groups. Targeted compound synthesis, loading onto DEB, and intra-arterial administration were feasible and successful in all cases. Serum liver enzyme levels increased in a dose dependent manner within 24 h and normalized within 3 days for 0.2/0.6 mg/kg SW43-DOX-89Y loaded onto DEB. The two rabbits treated with 1 mg/kg SW43-DOX-89Y had to be euthanized after 3/24 h due to worsening general condition. Histopathological necrosis increased over time in a dose depended manner with 95-100% tumor necrosis 3-7 days post treatment (0.6 mg/kg). SW43-DOX-89Y loaded onto DEB can be formulated and safely administered at a concentration of 0.6 mg/kg. Loading with radioactive isotopes (e.g., 86yttrium/90yttrium/177lutetium) to synthesize the targeted radio-chemoembolization drug-eluting bead (TRCE-DEB) concept drug is feasible.

Er,Cr:YSGG Laser Application for the Treatment of Periodontal Furcation Involvements.

OBJECTIVE: The purpose of this study was to evaluate the clinical use of an erbium, chromium: yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser in the management of root furcation involvements. BACKGROUND DATA: It has been suggested that the use of laser radiation within the periodontal pocket may be effective in periodontal treatment. However, very limited data from clinical trials exist directly comparing the use of the Er,Cr:YSGG laser to conventional root planing. MATERIALS AND METHODS: Thirty patients with chronic periodontitis were recruited. A total of 128 teeth with degree II or III furcation involvement were included in a split-mouth design such that the teeth on one side of the mouth were established as Group A and treated with the Er,Cr:YSGG laser and the teeth on the other side were established as Group B and treated with manual subgingival debridement. Changes in probing depth (PD), bleeding on probing (BOP), clinical attachment loss (CAL), and visual analogue scale (VAS) pain scores were compared between Groups A and B and within individuals over time at 6 and 12 weeks after treatment, testing the null hypothesis that there would be no clinical difference between treatment modalities. RESULTS: Both treatments significantly reduced the PD, CAL, and BOP in the diseased teeth with degree II or III furcation involvement. The reduction of PD and BOP at weeks 6 and 12 was significantly higher in Group A (laser treated) than in Group B. The VAS pain score was significantly lower in Group A than in Group B (p < 0.01). CONCLUSIONS: Pocket debridement with Er,Cr:YSGG laser is a safe, comfortable, and clinically effective means of subgingival debridement in periodontal therapy.

Incorporating Yttrium-90 trans-arterial radioembolization (TARE) in the treatment of metastatic pancreatic adenocarcioma: a single center experience.

BACKGROUND: The purpose of this retrospective study was to evaluate the efficacy of incorporating trans-arterial radioembolization (TARE) with systemic chemotherapy in the treatment of liver-dominant metastatic pancreatic ductal adenocarcinoma, with the aim of destroying liver metastases and improving patient outcomes. METHODS: We retrospectively evaluated 16 patients with liver-dominant metastatic pancreatic ductal adenocarcinoma who underwent TARE between February 2012 and August 2015; 15 of these patients also underwent concurrent systemic chemotherapy. Patient outcomes were assessed using Response Evaluation Criteria In Solid Tumors (RECIST), Version 1.1 and included disease response, median overall survival from the time of diagnosis of metastatic disease, and median overall survival following receipt of TARE. Treatment-related adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03. RESULTS: The median overall survival from the time of diagnosis of metastatic disease and following receipt of TARE was 22.0 and 12.5 months, respectively. Overall and liver specific disease response were assessed for 13 patients with follow-up imaging available at the time of study (range 2-13 weeks post TARE). Four patients (31 %) demonstrated partial response and five patients (38 %) had stable disease in the liver at follow-up. One patient developed grade 3 elevation of total bilirubin three months post-treatment and another patient developed radiation cholecystitis directly following TARE. No treatment-related grade 4 or 5 toxicities were seen. CONCLUSION: TARE can be safely combined with systemic chemotherapy for the treatment of liver-dominant metastatic pancreatic cancer. Patient outcomes following this treatment strategy are promising but prospective evaluations are needed to validate these preliminary findings.

808 nm Light-triggered and hyaluronic acid-targeted dual-photosensitizers nanoplatform by fully utilizing Nd(3+)-sensitized upconversion emission with enhanced anti-tumor efficacy.

The current near-infrared (NIR) light-induced photodynamic therapy (PDT) can enhance the tissue penetration depth to trigger photosensitizers (PSs) far from the surface. NIR-mediated PDT is still challenged by overheating effect on normal tissues, limited tumor selectivity and low reactive oxygen species (ROS) yields. Here we construct a dual-agent photosensitizing nanoplatform by combining UV-blue upconversion emitting NaYF4:Yb/Tm@NaYF4:Yb@NaNdF4:Yb@NaYF4 (labeled as UCNPs) multi-shell nanocrystals with titanium dioxide (TiO2, UV-light-excited PS) and hypocrellin A (HA, blue-light-excited PS), which can induce cancer cell apoptosis by 808 nm light-triggered and hyaluronic acid (Hyal)-targeted PDT. In this construction strategy, the crystallized TiO2 shells on the surface of UCNPs can play dual roles as UV-light excited PS and conjugation site for Hyal, and then Hyal is served as targeting-ligand as well as the carrier of HA simultaneously. The step-by-step reactive mode of loading PSs and modifying targeting-ligands is a controllable and ordered design based on the use of one intermediate product as the reaction site for the next component. The Nd(3+)-sensitized UCNPs with quenching reduction layer can efficiently convert 808 nm NIR light to UV-blue emission for simultaneous activation of two PSs with enhanced intracellular ROS generation. Through the in vitro and in vivo experiment results, the dual-photosensitizers nanoplatform presents enhanced anti-tumor efficacy by effective targeting cellular uptake and taking full advantage of upconversion emission, which may make a major step toward next generation of NIR-mediated PDT.

Patient and tumor characteristics predictive of an elevated hepatopulmonary shunt fraction before radioembolization of hepatic tumors.

OBJECTIVE: To determine whether any patient or hepatic tumor characteristics are predictive of hepatopulmonary shunt fraction when performed before radioembolization. MATERIALS AND METHODS: A retrospective review was performed on 190 patients who underwent preradioembolization hepatic arteriography with calculation of hepatopulmonary shunt fraction using technetium-99m-labeled macroaggregated albumin perfusion scintigraphy. Patient and tumor characteristics including imaging features were reviewed for correlation with absolute shunt fraction, shunt fraction greater than 10%, and shunt fraction greater than 20%. RESULTS: Most tumor types showed some cases of elevated shunt fraction greater than 10%. Six patients had a shunt fraction greater than 20%: four were hepatocellular carcinoma and two were neuroendocrine tumor metastases. Univariate analysis showed that dominant tumor diameter, hepatic tumor burden, vascular invasion, hepatic venous invasion, and hypervascularity on angiography were associated with a shunt fraction greater than 10%. Only dominant tumor diameter and vascular invasion were associated with a shunt fraction greater than 20%. On multivariate analysis, only tumor diameter (odds ratio 1.2) and hepatic venous invasion (odds ratio 23.0) were associated independently with an increased shunt fraction greater than 10%. CONCLUSION: Multiple patient and tumor-related characteristics were significantly correlated with the hepatopulmonary shunt fraction on univariate analysis. However, on multivariate analysis, only the dominant tumor diameter and presence of hepatic venous invasion were associated independently with a greater than 10% shunt fraction.

Modeling of Optimal Targeted Therapies Using Drug-Loaded Magnetic Nanoparticles for Liver Cancer.

To enhance locoregional therapies for liver cancer treatment, we propose in this study a mathematical model to optimize the transcatheter arterial delivery of therapeutical agents. To maximize the effect of the treatment and minimize adverse effects on the patient, different mathematical models of the tumor growth are considered in this study to find the optimal number of the therapeutic drug-loaded magnetic nanoparticles to be administered. Three types of therapy models are considered, e.g., angiogenesis inhibition therapy, chemotherapy and radiotherapy. We use state-dependent Riccati equations (SDRE) as an optimal control methodology framework to the Hahnfeldt's tumor growth formulation. Based on this, design optimal rules are derived for each therapy to reduce the growth of a tumor through the administration of appropriate dose of antiangiogenic, radio- and chemo-therapeutic agents. Simulation results demonstrate the validity of the proposed optimal delivery approach, leading to reduced intervention time, low drug administration rates and optimal targeted delivery.

Er:Yag Laser Treatment of Simple Snorers in an Outpatient Setting.

OBJECTIVE: Snoring occurs as a result of soft tissue vibration caused by a partial upper airway collapse during sleep. This study evaluated the effectiveness and potential adverse side effects associated with the use of a nonsurgical, erbium-doped yttrium aluminum garnet (Er:YAG) laser treatment for patients with snoring conditions. MATERIALS AND METHODS: In total, 33 patients with different degrees of snoring were analyzed retrospectively. All patients received three NightLase™ Er:YAG laser treatments. Results were measured using a follow-up questionnaire and then statistically analyzed. Any effects that occurred during the first year after treatment (i.e., short-term effects) were followed up with interviews. RESULTS: Laser treatment effectively reduced patients' snoring and achieved a 65% satisfaction rate after three treatments. The greatest improvement and satisfaction were experienced by patients aged ≥50 years. Patients reported additional benefits from this treatment including easier breathing, higher alertness, and increased focus. CONCLUSION: Nonsurgical Er:YAG laser treatment is an effective and minimally invasive procedure to reduce patient snoring and other sleep-disordered breathing symptoms. Patients reported minimal disadvantages including minor discomfort and a low risk of side effects.

Peripheral iridotomy for pigmentary glaucoma.

BACKGROUND: Glaucoma is a chronic optic neuropathy characterized by retinal ganglion cell death resulting in damage to the optic nerve head and the retinal nerve fiber layer. Pigment dispersion syndrome is characterized by a structural disturbance in the iris pigment epithelium (the densely pigmented posterior surface of the iris) that leads to dispersion of the pigment and its deposition on various structures within the eye. Pigmentary glaucoma is a specific form of open-angle glaucoma found in patients with pigment dispersion syndrome.Topcial medical therapy is usually the first-line treatment; however, peripheral laser iridotomy has been proposed as an alternate treatment. Peripheral laser iridotomy involves creating an opening in the iris tissue to allow drainage of fluid from the posterior chamber to the anterior chamber and vice versa. Equalizing the pressure within the eye may help to alleviate the friction that leads to pigment dispersion and prevent visual field deterioration. However, the effectiveness of peripheral laser iridotomy in reducing the development or progression of pigmentary glaucoma is unknown. OBJECTIVES: The objective of this review was to assess the effects of peripheral laser iridotomy compared with other interventions, including medication, trabeculoplasty, and trabeculectomy, or no treatment, for pigment dispersion syndrome and pigmentary glaucoma. SEARCH METHODS: We searched a number of electronic databases including CENTRAL, MEDLINE and EMBASE and clinical trials websites such as (mRCT) and ClinicalTrials.gov. We last searched the electronic databases on 2 November 2015. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that had compared peripheral laser iridotomy versus no treatment or other treatments for pigment dispersion syndrome and pigmentary glaucoma. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures for systematic reviews. Two review authors independently screened articles for eligibility, extracted data, and assessed included trials for risk of bias. We did not perform a meta-analysis because of variability in reporting and follow-up intervals for primary and secondary outcomes of interest. MAIN RESULTS: We included five RCTs (260 eyes of 195 participants) comparing yttrium-aluminum-garnet (YAG) laser iridotomy versus no laser iridotomy. Three trials included participants with pigmentary glaucoma at baseline, and two trials enrolled participants with pigment dispersion syndrome. Only two trials reported the country of enrollment: one - Italy, the other - United Kingdom. Overall, we assessed trials as having high or unclear risk of bias owing to incomplete or missing data and selective outcome reporting.Data on visual fields were available for one of three trials that included participants with pigmentary glaucoma at baseline. At an average follow-up of 28 months, the risk of progression of visual field damage was uncertain when comparing laser iridotomy with no iridotomy (risk ratio (RR) 1.00, 95% confidence interval (95% CI) 0.16 to 6.25; 32 eyes; very low-quality evidence). The two trials that enrolled participants with pigment dispersion syndrome at baseline reported the proportion of participants with onset of glaucomatous visual field changes during the study period. At three-year follow-up, one trial reported that the risk ratio for conversion to glaucoma was 2.72 (95% CI 0.76 to 9.68; 42 eyes; very low-quality evidence). At 10-year follow-up, the other trial reported that no eye showed visual field progression.One trial reported the mean change in intraocular pressure (IOP) in eyes with pigmentary glaucoma: At an average of nine months of follow-up, the mean difference in IOP between groups was 2.69 mmHg less in the laser iridotomy group than in the control group (95% CI -6.05 to 0.67; 14 eyes; very low-quality evidence). This trial also reported the mean change in anterior chamber depth at an average of nine months of follow-up and reported no meaningful differences between groups (mean difference 0.04 mm, 95% CI -0.07 to 0.15; 14 eyes; very low-quality evidence). No other trial reported mean change in anterior chamber depth. Two trials reported greater flattening of iris configuration in the laser iridotomy group than in the control group among eyes with pigmentary glaucoma; however, investigators provided insufficient data for analysis. No trial reported data related to mean visual acuity, aqueous melanin granules, costs, or quality of life outcomes.Two trials assessed the need for additional treatment for control of IOP. One trial that enrolled participants with pigmentary glaucoma reported that more eyes in the laser iridotomy group required additional treatment between six and 23 months of follow-up than eyes in the control group (RR 1.73, 95% CI 1.08 to 2.75; 46 eyes); however, the other trial enrolled participants with pigment dispersion syndrome and indicated that the difference between groups at three-year follow-up was uncertain (RR 0.91, 95% CI 0.38 to 2.17; 105 eyes). We graded the certainty of evidence for this outcome as very low.Two trials reported that no serious adverse events were observed in either group among eyes with pigment dispersion syndrome. Mild adverse events included postoperative inflammation; two participants required cataract surgery (at 18 and 34 months after baseline), and two participants required a repeat iridotomy. AUTHORS' CONCLUSIONS: We found insufficient evidence of high quality on the effectiveness of peripheral iridotomy for pigmentary glaucoma or pigment dispersion syndrome. Although adverse events associated with peripheral iridotomy may be minimal, the long-term effects on visual function and other patient-important outcomes have not been established. Future research on this topic should focus on outcomes that are important to patients and the optimal timing of treatment in the disease process (eg, pigment dispersion syndrome with normal IOP, pigment dispersion syndrome with established ocular hypertension, pigmentary glaucoma).