Comparisons of computer simulations and experimental data for capacitive hyperthermia using different split-phantoms.

INTRODUCTION: Several positive clinical trials have demonstrated that capacitive hyperthermia (CHT) improves the effectiveness of radiation therapy for the treatment of various cancer entities. However, the ability of CHT to induce significant heating throughout the body is under debate. OBJECTIVES: To perform a pilot study involving comparisons of computer simulations and experimental data using different split-phantoms to validate hyperthermia treatment modeling for pre-planning for a clinical CHT system and to investigate the feasibility of split-phantom measurements in capacitive hyperthermia. MATERIALS AND METHODS: The CHT system EHY-2030 (Oncotherm, Budapest, Hungary) was used. The system provides two electrode sizes, but only the smaller electrode, indicated as D200 electrode, was investigated in this pilot study. Horizontally and vertically splittable, different multi-slice phantoms with dielectric material properties simulating muscle and electrically low conductive fat were produced and heated. During the heating procedure, temperature-time curves were measured, and thermal images were captured. Specific absorption rate values were derived from the temperature rise (TR) values. Concomitantly, computer field simulations utilizing a detailed CAD-based model of the CHT system were performed using the simulation platform Sim4Life and compared with measurements. RESULTS: For the investigated electrode D200 the system power of 75 W was applied, which is half of the maximum power of 150 W and lies in the range of usual values for this electrode applied in patient treatments in our clinic. For 75 W, a heating of 3.6 °C in 6 min in a depth of 1 cm in an agar-based, muscle tissue-equivalent phantom was achieved. The addition of a 1 cm thick, synthetic, low dielectric fat layer reduced the TR up until a depth of 8.5 cm by on average around 38% (from 8.5 cm onwards the absolute local TR is similar, deviations are ≤0.1 °C). In terms of point-to-point absolute SAR comparison (without any normalization), up to a depth of 11 cm in the phantoms central vertical plot, the simulation differs from the measured TR points by on average 25% (ranging from 7% to 36%) for the homogeneous phantom and by on average 43% (ranging from 26% to 60%) for the inhomogeneous phantom. CONCLUSION: Computer simulations and experimental data were compared for the CHT system EHY-2030 using the D200 electrode, applying a thermal imaging technique for different vertically splittable phantoms. This pilot study data can be used as a guidance regarding the expected heating for this commonly used electrode size but also to further elucidate the significance of non-thermal anticancer effects. Further studies are needed for different sizes and geometries of electrodes and phantoms.

Generating and monitoring mild hyperthermia using a ring array ultrasound transducer.

OBJECTIVE: To demonstrate the feasibility of using a ring array ultrasound (US) transducer, guided by ultrasound tomography (UST), for generating and monitoring mild hyperthermia (MHTh). METHODS: In silico and in vitro experiments were designed to evaluate the efficacy of a ring array US transducer for generating MHTh and monitoring changes in temperature. In a series of in silico studies, we compared the acoustic focal profiles produced by a ring array US transducer transmitting at different frequencies and further investigated the effectiveness of UST-guidance in implementing aberration correction to enhance the focal profile. In vitro experiments evaluated the capability of using a ring array US transducer to generate and maintain MHTh and the accuracy of using UST to monitor temperature changes. RESULTS: The simulations demonstrated that a ring array US transducer achieves symmetrical and localized acoustic focusing. In a heterogenous tissue model, a ring array US transducer achieved a superior acoustic focus by implementing aberration correction with guidance from UST. In vitro experiments demonstrated the capability of a ring array US transducer to generate MHTh in a tissue-mimicking phantom in an average of 117 ± 18 s and subsequently maintain MHTh. Lastly, a ring array US transducer utilized UST to track temperature changes in a preheated water-filled inclusion while it passively cooled from 45 °C to 25 °C, with a maximum error of 0.58 °C. CONCLUSION: A ring array US transducer can noninvasively generate and monitor MHTh, overcoming many limitations of current clinical systems. The closed geometry of the transducer is optimal for acoustic focusing and UST-guidance allows for improved aberration correction in a heterogenous medium. Utilizing UST thermometry with the same ring array US transducer will allow for implementing an image-guided, temperature-controlled, all-acoustic MHTh system.

LipiFlow for the treatment of dry eye disease.

BACKGROUND: Meibomian gland dysfunction (MGD) is the most common underlying cause of dry eye disease (DED). MGD leads to pathological alteration of the composition or quantity of meibum, or both, which subsequently results in tear evaporation and the typical signs and symptoms associated with DED. The LipiFlow Thermal Pulsation System (LipiFlow) is a medical device used to treat MGD in office; however, it is unclear if LipiFlow can outperform other DED treatments. OBJECTIVES: To evaluate the effectiveness of LipiFlow for treating DED signs and symptoms and the safety of LipiFlow compared with sham or other available treatments for MGD in adults. SEARCH METHODS: The Cochrane Eyes and Vision Information Specialist searched the electronic databases for randomized controlled trials. There were no restrictions on language or date of publication. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, including the Cochrane Eyes and Vision Trials Register; 2022, Issue 6), MEDLINE Ovid, Embase.com, PubMed, LILACS (Latin American and Caribbean Health Science Information database), ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) electronic databases. We also examined the reference lists of identified trials, review articles, and guidelines for information about relevant trials that may not have been identified by our search strategy. We contacted investigators regarding ongoing trials. The last database search was performed on 24 October 2022. SELECTION CRITERIA: We included studies conducted in adults (over 18 years of age) with DED or MGD as defined by the primary trial investigators. We imposed no restrictions on race, ethnicity, or sex. We considered trials involving contact lens wearers if they were equally represented between groups. DATA COLLECTION AND ANALYSIS: We applied standard Cochrane methodology. MAIN RESULTS: We included 13 trials that randomized a total of 1155 participants (28 to 236 participants randomized per study). Six trials were conducted in the USA, three in China, two in Thailand, one in France, and one in Italy. Eight trials were of single-center design, while four trials were of multicenter design; one trial did not report the number of participating centers. Study characteristics The study population of the included trials was 66% female (range 48% to 80%), with an age range of 19 to 86 years. LipiFlow, used as a stand-alone intervention, was compared with basic warm compresses in five studies, thermostatic device in five studies, oral intervention in one trial, and topical dry eye medications in one trial. LipiFlow was also evaluated together with eyelid hygiene product versus eyelid hygiene products alone in one trial. Findings Five trials compared LipiFlow with a basic warm compress applied for varying durations and frequencies during the trial period; only one of these trials combined a warm compress with eyelid massage. Analyzing symptom scores by different questionnaires (Ocular Surface Disease Index [OSDI] and Standard Patient Evaluation of Eye Dryness [SPEED]) yielded conflicting evidence of a difference in symptoms between LipiFlow and basic warm compresses after four weeks. There was no evidence of a difference in meibomian gland expression, meibum quality, or tear breakup time when comparing LipiFlow with basic warm compresses. Another five trials compared LipiFlow with thermostatic devices. Analysis of symptom scores at four weeks showed that thermostatic devices had reduced OSDI scores by a mean difference (MD) of 4.59 (95% confidence interval [CI] 1.23 to 7.95; I2 = 0, P = 0.007; 553 participants; very low certainty evidence) as compared with LipiFlow. When we compared LipiFlow plus eyelid hygiene with eyelid hygiene alone, there was no evidence of difference in signs or symptoms at any time point evaluated. Only one trial compared LipiFlow with a topical DED medication (lifitegrast 5%). The single-trial estimate suggested that 5% lifitegrast may increase meibomian gland expression scores compared with LipiFlow at day 42 (MD -1.21, 95% CI -2.37 to -0.05; 50 participants; low certainty evidence) by using a meibomian gland expression scale of 0 to 8. One trial compared LipiFlow with an oral intervention (doxycycline), finding that LipiFlow may result in significantly better SPEED scores than doxycycline at three months (MD -4.00, 95% CI -7.33 to -0.67; 24 participants; very low certainty evidence). No other significant differences in signs or symptoms were found between LipiFlow and doxycycline at three months. We did not find any other statistically significant differences in symptoms or signs for any other analysis performed in this review at the one- to four-week time point. Adverse events No trial reported any intervention-related, vision-threatening adverse events. AUTHORS' CONCLUSIONS: LipiFlow performs similarly to other commonly used DED treatments with regard to DED signs and symptoms. The best available evidence was deemed to have a high level of bias, leading to low or very low certainty evidence. Additional research with adequate masking, a standardized testing methodology, and a sample representative of the MGD population is therefore needed before any firm conclusions can be drawn regarding comparative benefits and harms.

Efficacy and safety of the disposable eyelid warming masks in the treatment of dry eye disease due to Meibomian gland dysfunction.

BACKGROUND: Warm compresses are the routine treatment for Meibomian gland dysfunction (MGD) in daily life, but in order to achieve satisfactory efficacy, the treatment needs to be sustained over a long time, which can have an impact on the patient compliance. A more convenient warm compresses will help improve the patient compliance. Therefore, the purpose of the study is to investigate the efficacy and safety of the disposable eyelid warming masks for treatment of dry eye disease (DED) due to MGD. METHODS: This was a randomized, controlled, non-masked, two-center clinical trial. One hundred and forty-four patients were treated by the masks or the hot towel twice daily for 12 weeks. Patients were evaluated at baseline, 4-week and 12-week visits for subjective symptoms, objective signs and safety assessments, including ocular symptom scores, ocular surface disease index (OSDI), tear break-up time (BUT), corneal fluorescein staining (CFS), Schirmer I test (SIT), meibum quality, meibum expressibility, and adverse events (AEs). RESULTS: A totle of 134 patients were followed in the study. The mean age of the masks group (14 males and 52 females) and the hot towel group (20 males and 48 females) was 43.7 ± 13.5 years and 39.5 ± 13.9 years, respectively. At 4-week visit, there were significant statistical differences in ocular symptom scores, OSDI and CFS between two groups (P < 0.05). Except for SIT, the treatment group showed a greater improvement in subjective symptoms and objective signs than the control group at 12-week visit. (P < 0.05). In addition, 40 AEs occurred in 27 patients (37.5%) in the treatment group, and 34 AEs occurred in 21 patients (29.17%) in the control group. No serious AEs were reported. CONCLUSIONS: The masks had a good efficacy and safety in the treatment of DED due to MGD, and might offer an attractive treatment option for some patients. TRIAL REGISTRATION: The study was registered at Chinese Clinical Trial Registry (ChiCTR1900025443) on August 26, 2019.

Energy-Based Devices for the Treatment of Cutaneous Verrucae: A Systematic Review.

BACKGROUND: Warts are one of the most common benign neoplasms caused by human papillomavirus infection and often pose a therapeutic challenge. OBJECTIVE: To summarize the current evidence on the safety and efficacy of laser and energy-based devices for the treatment of cutaneous verrucae. METHODS: A comprehensive systematic review of the literature on laser and energy-based devices for the treatment of cutaneous verrucae was performed. RESULTS: A total of 904 unique studies were identified, of which 109 were included in this review. The most commonly used lasers as a single treatment modality for verrucae included the long-pulsed Nd:Yag (n = 20) and pulsed dye (n = 18) lasers. Other modalities included the CO2 ablative laser (n = 10), photodynamic therapy (n = 11), local hyperthermia (n = 11), microwave therapy (n = 2), and nanopulse stimulation (n = 1). Other studies combined energy-based modalities with additional treatments, such as retinoids, imiquimod, and intralesional bleomycin. Overall, such devices were generally well-tolerated, with only a mild side effect profile. CONCLUSION: Overall, the use of laser and energy-based devices is a safe and well-tolerated option for cutaneous verrucae that is relatively less invasive than surgical interventions. Future studies using more consistent outcome assessment tools will be valuable to help clinicians develop device-specific protocols and treatment regimens to ensure replicable and effective outcomes.

Exploring and validating heating dynamics in a radio-frequency electromagnetic field-based resonant chamber for mouse hyperthermia research.

Mild whole-body hyperthermia has been shown to have anti-tumor effects through an immune-modulating mechanism. Before it is widely applied in the clinic, tremendous mechanistic research in animals is necessary to adhere to evidence-based principles. The radio frequency electromagnetic field (RF-EMF) based heating facility could be a good choice for hyperthermia treatment, but the heating characteristics of a facility, including structure design, electromagnetic and thermal dosimetry, and the biologic effects of hyperthermia, need to be well elucidated. Here, we reported the heating characteristic study on a resonant chamber (RC) excited by a 1800 MHz solid source. The EMF in the RC was stirred by 24 static reflectors, which resulted in the standard deviation of electric field intensity being below 3 dB in the EM homogeneity evaluation. For the exposure scenario, six free-moving mice were loaded into separate cases and exposed simultaneously in the RC. The EMF energy absorption and distribution in exposed mice were calculated with the 12-plane-waves method of numerical simulation. Different levels of core body temperature increment in exposed mice were achieved through regulation of the source output power. Overexpression of heat shock proteins (HSPs) was detected in the liver, lung and muscle, but not in the brain of the exposed mice. The levels of representative inflammatory cytokines in the serum, TNF-α and IL-10 increased post RC exposure. Based on the heating characteristic study and validation, the applied RC would be a qualified heating system for mild whole-body hyperthermia effect research in mice.

Mild whole-body hyperthermia has potential anti-tumor effects by modulating the immune system. A radio frequency electromagnetic field (RF-EMF)-based heating facility emerges as a suitable option for hyperthermia treatment. However, a qualified heating facility for scientific research must elucidate its heating characteristics and validate the biological effects associated with hyperthermia. In this study, we report the characteristics of a rodent heating chamber using EMF energy. The special structure of the chamber not only achieved efficient EMF usage but also ensured the homogeneity in EMF spatial distribution, animal EM absorption, and EMF-caused biological effects. Our work may offer insights for designing a low-cost yet reliable heating facility for scientific research.

Efficacy of warm compresses in preserving perineal integrity and decreasing pain during normal labor: A systematic review and meta-Analysis.

The objective of the study was to assess the effect of warm compresses in preserving perineal integrity in women who delivered a single baby vaginally with cephalic presentation. We searched PubMed, Scopus, and the ISI Web of Science databases. Two researchers worked independently and conducted the study's search, selection, and extraction. We calculated the pooled risk ratio (R.R.)- for our categorical outcomes- and mean difference (M.D.)-for our continuous outcomes- using random or fixed-effect meta-analysis according to heterogenicity status. I2 test was used to detect heterogenicity. Studies were assessed for methodological quality using the Cochrane risk of bias assessment tool. Our study analyzed 13 controlled trials (n= 3947) to compare warm compresses versus not using it during vaginal delivery. The analysis revealed that warm compresses group had better outcomes regarding episiotomy, degree of perineal trauma (third and fourth degree), perineal trauma requiring suturing, and also in behavioral pain scales (severe muscle tense, being very restless, and constant grimacing) with the following R.R. and confidence intervals: (R.R.= 0.56, 95% C.I.[0.23, 1.37]), (R.R.= 0.69, 95% C.I.[0.54, 0.89], p= 0.004),( (R.R.= 0.37, 95% C.I.[0.18, 0.77], p= 0.004), and ( (R.R.= 0.42, 95% C.I.[0.23, 0.78], p= 0.006) respectively. We conclude that among primiparous women, warm compresses group showed better outcome in improving perineal comfort than a the good of women who did not receive warm compresses after delivery.

Reasons to go for Rezum steam therapy: an effective and durable outpatient minimally invasive procedure.

PURPOSE: In this review, we will discuss the state of the literature regarding Rezum and opportunities for its application in the treatment of BPH. METHODS: A comprehensive review of original research on convective water vapor thermal therapy (Rezum) was conducted. Articles related to transurethral resection of the prostate, holmium laser enucleation of the prostate, Aquablation, and greenlight photoselective vaporization of the prostate were reviewed for discussion. RESULTS: Rezum distinguishes itself from other treatment options by its durable improvement in objective clinical outcomes such as IPSS and BPH Impact Index, while being cost-effective and versatile in its ability to treat a variety of prostate gland morphologies. This treatment option shows good lower urinary tract symptom relief, especially in small-to-moderate prostate sizes (30-80 cc). The use of convective heat transfer is unique and allows for localized treatment, avoiding damage to surrounding structures, thus providing an excellent safety profile and sexual function preservation. CONCLUSION: The current evidence on Rezum warrants its consideration as a therapeutic alternative to transurethral surgery in selected patients.

Water vapor therapy (Rezum) for lower urinary tract symptoms related to benign prostatic hyperplasia: early results from the first Italian multicentric study.

PURPOSE: Rezum is the latest developed minimally invasive treatment for benign prostatic hyperplasia (BPH). We aimed to carefully assess the functional outcomes of patients treated with Rezum for BPH. METHODS: We prospectively followed 135 consecutive patients treated by Rezum at 5 institutions from June 2019 to August 2020. The International Prostate Symptom Score (IPSS), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-UI SF), the Overactive Bladder Questionnaire-Short Form (OAB-q SF) score, the International Index of Erectile Function (IIEF-5) and questions 9 and 10 to assess ejaculatory dysfunction were recorded. Election criteria were age > 18, no prior prostate interventions, IPSS ≥ 13, post-void residual ≤ 250 mL, prostate volume between 30 and 120 cc. RESULTS: The median operative time was 10.5 (IQR 8.7-15) min. All patients were dismissed few hours after surgery with indwelling urinary catheter that was removed after a median of 7 (IQR 7-10) days. A significantly decrease of IPSS from baseline at first (p = 0.001) and third (p < 0.0001) month after surgery was reported. No difference was reported in terms of ICIQ-UI SF score postoperatively. A mild reduction of the OAB-q SF score was reported at 1 month from surgery (p = 0.06) that turned significant at 3 months postoperatively (p < 0.0001). A slight but statistically significant increase of the IIEF-5 score was reported from baseline at 6 months (p = 0.04). Postoperatively, patients reported a significantly decrease of ejaculatory dysfunction after alpha-blocker interruption. CONCLUSION: Rezum treatment is a feasible minimally invasive option for patients with BPH symptoms and showed optimal early functional outcomes.

Laser Treatment of Pancreatic Cancer with Immunostimulating Interstitial Laser Thermotherapy Protocol: Safety and Feasibility Results From Two Phase 2a Studies.

PURPOSE: Ablative techniques have emerged as new potential therapeutic options for patients with locally advanced pancreatic cancer (LAPC). We explored the safety and feasibility of using TRANBERG|Thermal Therapy System (Clinical Laserthermia Systems AB, Lund, Sweden) in feedback mode for immunostimulating Interstitial Laser Thermotherapy (imILT) protocol, the newest ablative technique introduced for the treatment of LAPC. METHODS: The safety and feasibility results after the use of imILT protocol treatment in 15 patients of a prospective series of postsystemic therapy LAPC in two high-volume European institutions, the General and Pancreatic Unit of the Pancreas Institute, of the University of Verona, Italy, and the Department of Surgical Oncology of the Institut Paoli-Calmettes of Marseille, France, were assessed. RESULTS: The mean age was 66 ± 5 years, with a mean tumor size of 34.6 (±8) mm. The median number of cycles of pre-imILT chemotherapy was 6 (6-12). The procedure was performed in 13 of 15 (86.6%) cases; indeed, in two cases, the procedure was not performed; in one, the procedure was considered technically demanding; in the other, liver metastases were found intraoperatively. In all treated cases, the procedure was completed. Three late pancreatic fistulas developed over four overall adverse events (26.6%) and were attributed to imILT. Mortality was nil. A learning curve is necessary to interpret and manage the laser parameters. CONCLUSIONS: Safety, feasibility, and device handling outcomes of using TRANBERG|Thermal Therapy System with temperature probes in feedback mode and imILT protocol on LAPC were not satisfactory. The metastatic setting may be appropriate to evaluate the hypothetic abscopal effect.#NCT02702986 and #NCT02973217.

Effect of intra-arrest trans-nasal evaporative cooling in out-of-hospital cardiac arrest: a pooled individual participant data analysis.

BACKGROUND: Randomized trials have shown that trans-nasal evaporative cooling initiated during CPR (i.e. intra-arrest) effectively lower core body temperature in out-of-hospital cardiac arrest patients. However, these trials may have been underpowered to detect significant differences in neurologic outcome, especially in patients with initial shockable rhythm. METHODS: We conducted a post hoc pooled analysis of individual data from two randomized trials including 851 patients who eventually received the allocated intervention and with available outcome ("as-treated" analysis). Primary outcome was survival with favourable neurological outcome at hospital discharge (Cerebral Performance Category [CPC] of 1-2) according to the initial rhythm (shockable vs. non-shockable). Secondary outcomes included complete neurological recovery (CPC 1) at hospital discharge. RESULTS: Among the 325 patients with initial shockable rhythms, favourable neurological outcome was observed in 54/158 (34.2%) patients in the intervention and 40/167 (24.0%) in the control group (RR 1.43 [confidence intervals, CIs 1.01-2.02]). Complete neurological recovery was observed in 40/158 (25.3%) in the intervention and 27/167 (16.2%) in the control group (RR 1.57 [CIs 1.01-2.42]). Among the 526 patients with initial non-shockable rhythms, favourable neurological outcome was in 10/259 (3.8%) in the intervention and 13/267 (4.9%) in the control group (RR 0.88 [CIs 0.52-1.29]; p = 0.67); survival and complete neurological recovery were also similar between groups. No significant benefit was observed for the intervention in the entire population. CONCLUSIONS: In this pooled analysis of individual data, intra-arrest cooling was associated with a significant increase in favourable neurological outcome in out-of-hospital cardiac arrest patients with initial shockable rhythms. Future studies are needed to confirm the potential benefits of this intervention in this subgroup of patients.

Magnetic nanowires in biomedical applications.

Magnetic nanostructures and nanomaterials play essential roles in modern bio medicine and technology. Proper surface functionalization of nanoparticles (NPs) allows the selective bonding thus application of magnetic forces to a vast range of cellular structures and biomolecules. However, the spherical geometry of NPs poises a series of limitations in various potential applications. Mostly, typical spherical core shell structure consists of magnetic and non-magnetic layers have little tunability in terms of magnetic responses, and their single surface functionality also limits chemical activity and selectivity. In comparison to spherical NPs, nanowires (NWs) possess more degrees of freedom in achieving magnetic and surface chemical tenability. In addition to adjustment of magnetic anisotropy and inter-layer interactions, another important feature of NWs is their ability to combine different components along their length, which can result in diverse bio-magnetic applications. Magnetic NWs have become the candidate material for biomedical applications owing to their high magnetization, cheapness and cost effective synthesis. With large magnetic moment, anisotropy, biocompatibility and low toxicity, magnetic NWs have been recently used in living cell manipulation, magnetic cell separation and magnetic hyperthermia. In this review, the basic concepts of magnetic characteristics of nanoscale objects and the influences of aspect ratio, composition and diameter on magnetic properties of NWs are addressed. Some underpinning physical principles of magnetic hyperthermia (MH), magnetic resonance imaging (MRI) and magnetic separation (MS) have been discussed. Finally, recent studies on magnetic NWs for the applications in MH, MRI and MS were discussed in detail.

Enhanced Percutaneous Delivery of Beta-Blockers Using Thermal Resurfacing Drug Delivery System for Topical Treatment of Infantile Hemangiomas.

BACKGROUND: Infantile hemangiomas (IHs) are the most common vascular tumors in children. In the past few years, topical beta-blockers (bBs) have been reported to be an effective treatment of superficial IHs. OBJECTIVE: We sought to evaluate the clinical effectiveness and safety profile of enhanced percutaneous delivery of bBs for the treatment of IH. METHODS: A retrospective study of all cases of IHs treated with enhanced percutaneous delivery of bBs between 2018 and 2019 was performed. Epidemiologic, clinical, and treatment data, including effectiveness score and safety, were reviewed. RESULTS: The study included 11 patients with a total of 11 IHs. Of the total number of IHs, 7 (63.7%) showed a good response to treatment and 4 (36.3%) had a partial response; thus all patients (100%) had good or partial response to treatment. No systemic or local adverse effects were reported. LIMITATIONS: This is an uncontrolled retrospective study. CONCLUSION: Enhanced percutaneous delivery of bBs is a safe and efficient topical therapy for IH.

Design of Site-Specific Microwave Phased Array Hyperthermia Applicators Using 434 MHz Reduced Cavity-Backed Patch Antenna.

Cancers of the neck, breast, and lower extremities are common malignancies diagnosed in India with a higher incidence of advanced-stage disease. Phased array (PA) applicators reported for hyperthermia treatment (HT) of the breast have small focal region and high cross-coupling, and those reported for lower extremities provide regional heating and limited steering. In this study, we present the numerical design of site-specific PA applicators for HT of large solid tumors in the neck, breast, and lower extremities using a miniaturized 434 MHz cavity-backed water-loaded patch antenna. The fabricated antenna has 38 × 36 mm2 aperture, more than 90% power coupling, 25 MHz bandwidth, and good agreement between simulated and measured specific absorption rate (SAR) in phantom. The site-specific applicators demonstrated less power reflection (<-17.9 dB) and cross-coupling (<-26.8 dB) for 5 mm inter-ring spacing. SAR indicators for 64 cc tumor at varying locations in simplified layered three-dimensional (3D) tissue models of the neck, breast, and leg showed average power absorption ratio (aPAratio ) ≥ 3.16, target to hotspot quotient (THQ) ≥ 0.57, 25% iso-SAR coverage (TC25 ) ≥ 81%, and 50% iso-SAR coverage (TC50 ) ≥51.8%. Simulation results of site-specific applicators for 3D inhomogeneous patient models showed aPAratio ≥ 5.98, THQ ≥ 0.9, TC50 ≥ 86%, and 100% TC25 for all sites. It is concluded that the 434 MHz miniaturized cavity-backed patch antenna can be used to develop high-density PA applicators with 12-24 antennas for HT of large solid tumors (≥4 cm) in the neck, breast, and lower extremities with 3D steering ability and less cross-coupling (≤-26.8 dB). © 2020 Bioelectromagnetics Society.

Tumour shape-dependent microwave hyperthermia using a novel coaxial micro-cut slot antenna.

Given that the effectiveness of interstitial hyperthermia for cancer treatment is related to the temperature achieved during the ablation process, there is a need for an accurate understanding of the required temperature distribution which is affected by the physical shape and form of tumours. Although a maximum peak temperature value and minimum backward heating are desired, the temperature distribution needs to be not only high but also uniformly extended over a section instead of at one peak point, especially when a roughly oval-shaped tumour is aligned with the antenna. In this case, achieving a high temperature peak destroys only the central cancerous cells after the first minutes of ablation, leaving the cells on the side alive. In this paper, a complex model was extended for the study of the heat distribution of an antenna over a porous liver composed of blood, cancerous cells, and normal tissue. Three different types of antenna were analysed: single-slot, double-slot, and dipole-tip. A novel structure made up of the single-slot antenna with a micron cut, named the micro-cut slot (MCS) antenna, was proposed and analysed. Thanks to the new structure, high uniform temperature distribution with minimum backward heating was achieved. The extended model equations, which encompass a coupled nonlinear set of transient Maxwell's electromagnetic equations, extended Darcy-Brinkman equation, and local thermal non-equilibrium equations for porous medium approximation, were solved numerically using the novel alternating direction implicit, finite-difference time-domain approach. The results showed that each type of antenna could be useful if chosen according to the shape of the tumour. In comparison with previously used antennas, the MCS antenna presented a good combination of the required goals of achieving uniform high temperature distribution and minimum backward heating.

Effectiveness of skin-heating using a water-perfused suit as passive and post-exercise heat acclimation strategies.

The purpose of the present study was to evaluate the effectiveness of passive and post-exercise heat acclimation strategies through directly heating the skin with a water-perfused suit. Nineteen young males participated in the heat acclimation (HA) protocols for 10 days, which were conducted at an air temperature of 33oC with 60%RH. The exercise-only condition (N = 6) conducted 1-h treadmill walking (6 km·h-1) followed by 1-h rest. The post-exercise passive-heating condition (N = 6) wore the suit (inflow water temperature 44.2oC) for 1-h after 1-h walking. The passive-heating condition (N = 7) donned the suit for 2 h. Heat tolerance tests (leg immersion in 42oC water for 60 min) were conducted before and after the training to evaluate changes due to the 10-day intervention. Reflecting that suit-wearing for 10 days as both passive and post-exercise HA strategies can effectively induce adaptive changes, significant interaction effects appeared in: increase or decrease in mean skin temperature (P < 0.05) and elevation in whole-body sweat rate (P < 0.05). Reduction in rectal temperature (P < 0.05) and blood pressure (P < 0.05) were found most prominently in the passive-heating condition. These results indicate that this new method of heat acclimation training, donning a skin-heating water-perfused suit, can generate thermoregulatory benefits. The passive HA intervention could be applied to individuals for whom doing exercise regularly are not feasible.

Optimization of the Preparation of Magnetic Liposomes for the Combined Use of Magnetic Hyperthermia and Photothermia in Dual Magneto-Photothermal Cancer Therapy.

In this work, we aimed to develop liposomal nanocomposites containing citric-acid-coated iron oxide magnetic nanoparticles (CMNPs) for dual magneto-photothermal cancer therapy induced by alternating magnetic field (AMF) and near-infrared (NIR) lasers. Toward this end, CMNPs were encapsulated in cationic liposomes to form nano-sized magnetic liposomes (MLs) for simultaneous magnetic hyperthermia (MH) in the presence of AMF and photothermia (PT) induced by NIR laser exposure, which amplified the heating efficiency for dual-mode cancer cell killing and tumor therapy. Since the heating capability is directly related to the amount of entrapped CMNPs in MLs, while the liposome size is important to allow internalization by cancer cells, response surface methodology was utilized to optimize the preparation of MLs by simultaneously maximizing the encapsulation efficiency (EE) of CMNPs in MLs and minimizing the size of MLs. The experimental design was performed based on the central composite rotatable design. The accuracy of the model was verified from the validation experiments, providing a simple and effective method for fabricating the best MLs, with an EE of 87% and liposome size of 121 nm. The CMNPs and the optimized MLs were fully characterized from chemical and physical perspectives. In the presence of dual AMF and NIR laser treatment, a suspension of MLs demonstrated amplified heat generation from dual hyperthermia (MH)-photothermia (PT) in comparison with single MH or PT. In vitro cell culture experiments confirmed the efficient cellular uptake of the MLs from confocal laser scanning microscopy due to passive accumulation in human glioblastoma U87 cells originated from the cationic nature of MLs. The inducible thermal effects mediated by MLs after endocytosis also led to enhanced cytotoxicity and cumulative cell death of cancer cells in the presence of AMF-NIR lasers. This functional nanocomposite will be a potential candidate for bimodal MH-PT dual magneto-photothermal cancer therapy.

Polymeric Reactor for the Synthesis of Superparamagnetic-Thermal Treatment of Breast Cancer.

Engineered superparamagnetic iron oxide nanoparticles (SPIONs) have been studied extensively for their localized homogeneous heat generation in breast cancer therapy. However, challenges such as aggregation and inability to produce sub-10 nm SPIONs limit their potential in magnetothermal ablation. We report a facile, efficient, and robust in situ method for the synthesis of SPIONs within a poly(ethylene glycol) (PEG) reactor adsorbed onto reduced graphene oxide nanosheets (rGO) via the microwave hydrothermal route. This promising modality yields crystalline, stable, biocompatible, and superparamagnetic PEGylated SPION-rGO nanocomposites (NCs) with uniform dispersibility. Our findings show that rGO acts as a breeding ground for the spatially distributed nanosites around which the ferrihydrite seeds accumulate to ultimately transform into immobilized SPIONs. PEG, in parallel, acts as a critical confining agent physically trapping the accumulated seeds to prevent their aggregation and create multiple domains on rGO for the synthesis of quantum-sized SPIONs (9 ± 1 nm in diameter). This dual functionality (rGO and PEG) exhibits a pronounced effect on reducing both the aggregation and the sizes of fabricated SPIONs as confirmed by the scanning transmission electron microscopy images, dynamic light scattering analyses, and the specific absorption rates (SARs). Reduced aggregation lowered the toxicity of NCs, where PEGylated SPION-rGO NCs are more biocompatible than PEGylated SPIONs, showing no significant induction of cell apoptosis, mitochondrial membrane injury, or oxidative stress. Significantly less lactate dehydrogenase release and hence less necrosis are observed after 48 h exposure to high doses of PEGylated SPION-rGO NCs compared with PEGylated SPIONs. NCs induce local heat generation with a SAR value of 1760 ± 97 W/g, reaching up to 43 ± 0.3 °C and causing significant MCF-7 breast tumor cell ablation of about 78 ± 10% upon applying an external magnetic field. Collectively, rGO and PEG functionalities have a synergistic effect on improving the synthesis, stability, biocompatibility, and magnetothermal properties of SPIONs.

Murine Models of Intraperitoneal Perfusion for Disseminated Colorectal Cancer.

BACKGROUND: Reproduction of the perfusion used in therapy (hyperthermic intraperitoneal chemotherapy) procedures preclinically represents a valuable asset for investigating new therapeutic agents that may improve patient outcomes. This article provides technical descriptions of our execution of closed and open "coliseum" abdominal perfusion techniques in a mouse model of peritoneal carcinomatosis of colorectal cancer. MATERIALS AND METHODS: BALB/c mice presenting with disseminated colorectal cancer (CT26-luciferin cells) underwent 30-min perfusions mimicking either the closed perfusion or the coliseum perfusion technique. Disease burden was monitored by bioluminescence signaling using an in vivo imaging system. Perfusion circuits consisted of single inflow lines with either a single or dual outflow line. RESULTS: Twelve mice presenting with disseminated disease underwent the closed perfusion technique. Surgical complications included perfusate leakage and organ constriction/suction into the outflow line(s). Nine mice underwent the coliseum perfusion technique with surgical debulking, using bipolar cauterization to remove tumors attached to the peritoneum. All mice survived the coliseum perfusion with limited intraoperative complications. CONCLUSIONS: Fewer intraoperative complications were experienced with our coliseum perfusion technique than the closed perfusion. The methods described here can be used as a guideline for developing future perfusion murine models for investigating perfusion models useful for delivery of chemotherapy or other tumor-sensitization agents, including selective targeted agents, nanoparticles, and heat.