Safety and Efficacy of a Thermomechanical Fractional Injury Device for Periorbital Rhytides.

BACKGROUND: Periorbital rejuvenation is a common cosmetic concern. A fractional thermomechanical skin rejuvenation system was developed to offer clinical improvements from direct heat transfer. OBJECTIVE: A prospective study evaluated the efficacy and safety of the device for periorbital fine lines and wrinkles. MATERIALS AND METHODS: Subjects with moderate-to-severe periorbital rhytides were enrolled and underwent 4 monthly treatments with a novel device using thermomechanical fractional injury (Tixel 2; Novoxel, Netanya, Israel). RESULTS: Fifty-one subjects were enrolled. Mean age was 56.8 years, and 88.2% were women. Fitzpatrick skin Types I to IV were included. For Fitzpatrick Wrinkle Classification System (FWCS), mean baseline score was 5.7. Per investigator, there was a mean 2.0-grade improvement in FWCS at 3-month follow-up ( p < .0001). Per 3 blinded physician raters, there was a mean improvement of 2.2 ( p < .0001), 2.0 ( p < .0001), and 1.2 ( p < .0001) in FWCS at 3-month follow-up. Each of the raters correctly identified posttreatment images for 87.5%, 77.1%, and 75.0% of subjects. At least 2 raters agreed on grading 83.3% of subjects as responders. There were no severe adverse events. Subjects experienced minimal pain and downtime. CONCLUSION: A novel device using thermomechanical fractional injury was demonstrated to be safe and effective in the treatment of periorbital rhytides.

Durability of Response to Primary Chemoablation of Low-Grade Upper Tract Urothelial Carcinoma Using UGN-101, a Mitomycin-Containing Reverse Thermal Gel: OLYMPUS Trial Final Report.

PURPOSE: Our goal was to evaluate long-term safety and durability of response to UGN-101, a mitomycin-containing reverse thermal gel, as primary chemoablative treatment for low-grade upper tract urothelial carcinoma. MATERIALS AND METHODS: In this open-label, single-arm, multicenter, phase 3 trial (NCT02793128), patients ≥18 years of age with primary or recurrent biopsy-proven low-grade upper tract urothelial carcinoma received 6 once-weekly instillations of UGN-101 via retrograde catheter to the renal pelvis and calyces. Those with complete response (defined as negative ureteroscopic evaluation, negative cytology and negative for-cause biopsy) 4-6 weeks after the last instillation were eligible for up to 11 monthly maintenance instillations and were followed for ≥12 months with quarterly evaluation of response durability. Durability of complete response was determined by ureteroscopic evaluation; duration of response was estimated by the Kaplan-Meier method. Treatment-emergent adverse events (TEAEs) were monitored. RESULTS: Of 71 patients who initiated treatment, 41 (58%) had complete response to induction therapy and consented to long-term followup; 23/41 patients (56%) remained in complete response after 12 months (95% CI 40, 72), comprising 6/12 (50%) who did not receive any maintenance instillations and 17/29 (59%) who received ≥1 maintenance instillation. Kaplan-Meier analysis of durability was estimated as 82% (95% CI 66, 91) at 12 months. Ureteric stenosis was the most frequently reported TEAE (31/71, 44%); an increasing number of instillations appeared to be associated with increased incidence of urinary TEAEs. CONCLUSIONS: Durability of response to UGN-101 with or without maintenance treatment is clinically meaningful, offering a kidney-sparing therapeutic alternative for patients with low-grade disease.

Efficacy and safety of a thermal fractional skin rejuvenation system (Tixel) for the treatment of facial and/or scalp actinic keratoses.

Actinic keratoses are common cutaneous lesions with a potential to progress to invasive squamous cell carcinoma. Therefore, treatment is crucial. The Tixel® is a noninvasive thermomechanical device designed to transfer heat to the upper dermis in a controlled manner according to a predetermined setting. This study aimed to evaluate the safety and efficacy of a thermomechanical fractional skin resurfacing technology for the treatment of facial and scalp actinic keratoses. A prospective, open-label, before-after study was conducted in a tertiary medical centre from May 2020 to April 2021. Patients presenting with facial/scalp actinic keratoses of mild-to-moderate thickness underwent 2 or 3 Tixel treatments (depending on clinical improvement), 3-4 weeks apart. The reduction in lesion count and overall improvement in appearance were assessed by clinical examination and digital photography. Findings were compared between baseline and follow-up at 3 months after the last treatment session. Patient satisfaction was evaluated by questionnaire, and adverse effects were documented. A total of 20 patients participated in the study. All completed 2-3 treatments and follow-up visits. Assessment of digital photographs was performed by 2 assessors blinded to the timepoint at which each photo was taken (before or after treatment). The average number of lesions at baseline was 9.8 (± 4.8) and the mean reduction in lesion count was 7.9 (± 4.4) (80.6%). Complete clearance was observed in 31.6% of patients. No adverse effects were noted during treatment and follow-up. Most patients reported being "very satisfied" or "satisfied" with the treatment results (85%) and experience (95%). Treating facial and scalp actinic keratoses with the Tixel device was found to be effective and safe.

A comprehensive approach to risk factors for upper arm morbidities following breast cancer treatment: a prospective study.

BACKGROUND: Breast cancer surgery frequently causes deficiencies in shoulder functioning. The study pourpode is to identify risk factors for prolonged pain, reduction in function, and decrease in range of motion (ROM) in BC patients. METHODS: A prospective cohort study was designed in a private hospital; between October 2018 and April 2019 with a follow-up of 6 months. Patients following BC surgery, were divided by arm morbidities, and the different risk facrors were evaluated using univariate analysis and logistic regression. RESULTS: A total of 157 patients were included in the study. Risk factors for functional disabilities included; pain levels during hospitalization NPRS 1.2 (±0.8) compared to patients with no disabilities 0.5 ± 0.7 (p = .006), the size of tumors more than 1.4 ± 0.8 cm. compared with no morbidities 0.8 ± 0.9 cm. (p = .046), and breast reconstructions (p = .030). Risk factors for prolonged pain includes mastectomy (p = .006), breast reconstruction (p = .011), more than three dissected lymph nodes (p = .002), the presence of preoperative pain (p < .001), in-hospital pain (p < .001), axillary web syndrome (p < .001) and lymphedema (p < .001). Risk factors for decreased ROM were more than three dissected lymph nodes (p = .027), radiation (p = .018), and the size of dissected tissue (p = .035). Postoperative physical therapy appears to reduce the incidence of prolonged pain (p = .013) and regular physical activity may reduce long term functional disabilities (p = .021). CONCLUSIONS: Upper arm morbidity following BC treatments affect up to 70% of the patients. Identifying the different risk and beneficial factors may improve awareness among physicians to refer patients to early rehabilitation programs and thus avoid chronic morbidity and improve the course of recovery. TRIAL REGISTRATION: The study was registered in Clinical trial with the ID number: NCT03389204 .

Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open-label, single-arm, phase 3 trial.

BACKGROUND: Most patients with low-grade upper tract urothelial cancer are treated by radical nephroureterectomy. We aimed to assess the safety and activity of a non-surgical treatment using instillation of UGN-101, a mitomycin-containing reverse thermal gel. METHODS: In this open-label, single-arm, phase 3 trial, participants were recruited from 24 academic sites in the USA and Israel. Patients (aged ≥18 years) with primary or recurrent biopsy-proven, low-grade upper tract urothelial cancer (measuring 5-15 mm in maximum diameter) and an Eastern Cooperative Oncology Group performance status score of less than 3 (Karnofsky Performance Status score >40) were registered to receive six instillations of once-weekly UGN-101 (mitomycin 4 mg per mL; dosed according to volume of patient's renal pelvis and calyces, maximum 60 mg per instillation) via retrograde catheter to the renal pelvis and calyces. All patients had a planned primary disease evaluation 4-6 weeks after the completion of initial therapy, in which the primary outcome of complete response was assessed, defined as negative 3-month ureteroscopic evaluation, negative cytology, and negative for-cause biopsy. Activity (complete response, expected to occur in >15% of patients) and safety were assessed by the investigator in all patients who received at least one dose of UGN-101. Data presented are from the data cutoff on May 22, 2019. This study is registered with ClinicalTrials.gov, NCT02793128. FINDINGS: Between April 6, 2017, and Nov 26, 2018, 71 (96%) of 74 enrolled patients received at least one dose of UGN-101. 42 (59%, 95% CI 47-71; p<0·0001) patients had a complete response at the primary disease evaluation visit. The median follow-up for patients with a complete response was 11·0 months (IQR 5·1-12·4). The most frequently reported all-cause adverse events were ureteric stenosis in 31 (44%) of 71 patients, urinary tract infection in 23 (32%), haematuria in 22 (31%), flank pain in 21 (30%), and nausea in 17 (24%). 19 (27%) of 71 patients had study drug-related or procedure-related serious adverse events. No deaths were regarded as related to treatment. INTERPRETATION: Primary chemoablation of low-grade upper tract urothelial cancer with intracavitary UGN-101 results in clinically significant disease eradication and might offer a kidney-sparing treatment alternative for these patients. FUNDING: UroGen Pharma.

Risk factors for long-term arm morbidities following breast cancer treatments: A systematic review.

PURPOSE: To examine the risk factors for arm morbidity following breast cancer treatments, taking a broad view of all types of physical morbidity, including prolonged pain, lymphedema, decreased range of motion, and functional limitations. METHODS: A systematic literature review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. Studies exploring the risk factors for prolonged arm morbidity following breast cancer surgery and treatments were included. The studies were assessed independently according to pre-eligibility criteria, following data extraction and methodological quality assessment. RESULTS: 1,242 articles were identified. After removing duplicates, the full texts of 1,153 articles were examined. Sixty-nine of these articles met the criteria and were included in the review. These 69 articles identified 29 risk factors for arm morbidity following treatments for breast cancer. The risk of bias was evaluated using NIH study quality assessment tools. The studies reviewed were published between 2001 and 2021 and included a total of 22,886 patients who were followed up for between three months and 10 years. CONCLUSIONS: The main risk factors for long-term morbidity are removal of lymph nodes from the axilla, body mass index >30, having undergone a mastectomy, the stage of the disease, radiation therapy, chemotherapy, infection and trauma to the affected arm after surgery. An understanding of the risk factors for prolonged arm morbidity after surgery can help doctors and therapists in making personalized decisions about the need and timing of rehabilitation treatments.

A pilot study evaluating the effect of early physical therapy on pain and disabilities after breast cancer surgery: Prospective randomized control trail.

BACKGROUND: Morbidity of the shoulders after breast cancer (BC) surgery is a common side effect that includes; persistent pain, function limitation, and decreased range of motion (ROM). This study examines the effect of early physical therapy (PT) and patient's education on these morbidities. METHODS: A prospective, randomized clinical trial was conducted at a single medical center from October 2018 until April 2019. Women scheduled for breast cancer surgery were divided into intervention or control as standard care. The intervention included a PT treatment that included exercise instructions from the first postoperative day. Pain levels, upper limb function, ROM, and complications were measured. RESULTS: The study includes 157 women (mean age, 52.2 ± 12.9). Early PT reduced pain levels at the first month (NPRS 1.5 ± 1.2) and six months (NPRS 0.5 ± 0.8), compared with control (NPRS 2.1 ± 1.4, 1.0 ± 1.2), p = 0.019 and p = 0.011, respectively. Subdivision of the sample into small and extensive surgeries revealed additional positive effect for the intervention six months postoperatively on functional disabilities, p = 0.004 and p = 0.032 respectively. No complications attributable to the intervention were recorded. CONCLUSIONS: Early PT and patient education reduces pain levels, and may improve function disabilities, without causing postoperative complications, although a larger study is needed to achieve unequivocal results.

Effect of physical activity levels on oncological breast surgery recovery: a prospective cohort study.

After breast cancer (BC) surgery, women may experience a physical decline. The effect of physical activity (PA) on the course of recovery after BC surgery has not yet been thoroughly examined. To analyze the impact of physical activity performed by women undergoing breast cancer surgery on measures of function, range of motion, and self-efficacy. A prospective study was carried out in 157 patients who underwent surgery for BC between October 2018 and April 2019, divided into four groups according to the intensity of PA with 6 months follow-up. 50 sedentary patients and 107 active patients were enrolled; the mean age was 52.6. Women who performed physical activity, moderate to vigorous, demonstrated lower function disabilities (QuickDASH 2.22) compared with inactivity or light physical activity (QuickDASH 7.0, p < 0.001), with better shoulder flexion (159.0° vs. 150.7°, p = 0.007) and abduction (159.5° vs. 152.2°, p = 0.008). Higher PA levels, displayed in higher self-efficacy reports (9.5 vs. 8.8, p = 0.002), and return to prior job status (0.005). The PA level does not influence pain at one, three and 6 months postoperatively (p = 0.278, p = 0.304 and p = 0.304 respectively). High PA levels increase the risk of axillary web syndrome (p = 0.041), although, it reduces the incidence of chronic pain (p = 0.007). Women who practice physical activity recover better from BC surgery than sedentary women. The higher the intensity and frequency of training, the better the results. Vigorous activity cause axillary web syndrome, despite, it has a beneficial effect on lowering the rate of chronic pain.

Lymphatic treatments after orthopedic surgery or injury: A systematic review.

BACKGROUND: Orthopedic injuries in conjunction with extensive damage to tissues, bones and blood vessels, usually require a long recovery. Associated consequences are pain, movement limitations, decreased function and occasionally, prolonged edema, which can delay or interfere with the healing process. Lymphatic and compression therapy have become increasingly common, intending to reduce edema and pain, thus, promoting the recovery process. AIMS: To examine the efficacy of methods commonly used to reduce edema after orthopedic injury or surgery, i.e. decongestive therapy, manual lymphatic drainage, and compression bandaging. METHODS: English literature search was undertaken in January 2019, in the following databases: Cochrane Library, MEDLINE, PEDro. INCLUSION CRITERIA: randomized controlled or quasi-controlled trials in adults who have edema or pain after recent limb trauma or surgery. Two independent assessors rated study quality and risk of bias using the PRISMA recommendations and PEDro score. RESULTS: We evaluated 71 papers. After excluding duplicated and irrelevant papers, 15 met the eligibility criteria (6 on lymphatic treatment and 9 on compression). Quality of papers ranged from 3 to 7 on PEDro score; of them, 13 were 1b Level of Evidence and two were 1c. CONCLUSION: After elective surgeries, when the significant edema appears or persists beyond recovery time, complex decongestive therapy and manual edema mobilization should be recommended in addition to conventional physical therapy. In acute injuries such as ankle or distal radius fractures, lymphatic treatments and compression bandaging should be considered as part of the therapeutic protocol. Nine studies evaluated different compression modalities found that only multilayer and long stretch compression significantly reduce edema.

Inhibition of oral peroxidase activity by cigarette smoke: in vivo and in vitro studies.

Oral peroxidase (OPO), the pivotal enzyme in the salivary antioxidant system, seems to be of paramount importance in the oral defense mechanism, especially against the attack of free radicals related to cigarette smoke (CS) and the evolution of oral cancer. The major inducer of oral cancer is exposure to tobacco, which is responsible for 50-90% of cases worldwide. The purpose of our study was to elucidate the outcome of interaction between CS and OPO in smokers and nonsmokers. After smoking a single cigarette, a sharp drop of OPO activity was observed in both groups: 42.5% in smokers and 58.5% in nonsmokers (p <.05). After 30 min, the level of activity returned to 90-100% of the presmoking level, presumably due to the secretion of new saliva into the oral cavity. The difference between the two groups was also observed after exposure of saliva to one cigarette in smoking flasks (in vitro studies); however, as expected, no recovery of activity was observed in either group. Similarly, the OPO activity loss was accompanied by increased carbonylation of the salivary proteins, an indicator of the oxidative damage to proteins. These results may be of great clinical importance, as heavy smokers smoke 20 cigarettes or more on a daily basis. Accordingly, most of the time the oral epithelium of heavy smokers is essentially unprotected by OPO against the deleterious effects of thiocyanate ions and hydroxyl radicals produced by unremoved hydrogen peroxide in the presence of the salivary redox-active metal ions. This may pave the way for the CS-induced and saliva-mediated initiation and progression of oral cancer.

Characterization of the differentiated antioxidant profile of human saliva.

Saliva is armed with various defense mechanisms, such as the immunological and enzymatic defense systems. In addition, saliva has the ability to protect the mucosa against mechanical insults and to promote its healing via the activity of epidermal growth factor. However, another defense mechanism, the antioxidant system, exists in saliva and seems to be of paramount importance. The most interesting finding of the present study was the demonstration of the existence of much higher concentrations of the various salivary molecular and enzymatic antioxidant parameters in the parotid saliva compared with the submandibular/sublingual saliva. For example, peroxidase, superoxide dismutase, uric acid, and total antioxidant status were higher in resting parotid saliva compared with resting submandibular/sublingual saliva by 2405, 235, 245, and 147%, respectively. Another important finding was the distinction between the salivary antioxidant system and the immunological and enzymatic protective systems, as represented by the salivary concentrations of secretory IgA and lysozyme, respectively. These findings suggest that the profound antioxidant capacity of saliva secreted from parotid glands is related either to the different physiological demands related to eating (parotid predominance), to oral integrity maintenance (submandibular/sublingual predominance), or to the high content of deleterious redox-active transitional metal ions present in parotid saliva. This also may signify that our oral cavity environment is only partially protected against oxidative stress during most of the day and night.

Effect of cigarette smoke on oral peroxidase activity in human saliva: role of hydrogen cyanide.

Peroxidase activity in human saliva is composed of salivary peroxidase (80%), of salivary glandular origin, and myeloperoxidase (20%), of leukocyte origin. The term oral peroxidase (OPO) is used here to denote the total activity of both peroxidase species. Using the 2-nitrobenzoic acid-thiocyanate assay, OPO activity was measured in the saliva of nonsmokers after exposure to gas-phase cigarette smoke (CS) in an in vitro system using three puffs of CS in 1 h. A marked decrease of 76% of activity was observed following three puffs of CS. In order to elucidate the mechanism by which CS caused loss of OPO activity, several oxidants and antioxidants were applied to saliva in vitro in the presence and absence of CS. No protection for CS-induced loss of OPO activity occurred in the presence of glutathione, N-acetylcysteine, ascorbic acid, or Desferal. Exposure of saliva to purified aldehydes present in CS did not significantly affect OPO loss of activity. Similarly, ascorbic acid in the presence of FeCl(3) and nicotine also had no effect on OPO activity. Exposure of OPO to cyanate at levels present in CS caused a 65-70% loss of OPO activity, which was reversible after 24 h of dialysis. Moreover, hydroxocobalamin, a known cyanate chelator, could prevent CS- and potassium cyanide-induced inactivation of OPO by 70-90%. The results show that hydrogen cyanide, known to be present in microgram amounts per cigarette, is likely to be the species in CS responsible for loss of salivary OPO activity. The finding of reduced salivary OPO levels after CS exposure may represent a contributory mechanism for CS-related compromises in antimicrobial defenses in the aerodigestive tract.