Targeting Vascular Impairment, Neuroinflammation, and Oxidative Stress Dynamics with Whole-Body Cryotherapy in Multiple Sclerosis Treatment.

Multiple sclerosis (MS), traditionally perceived as a neurodegenerative disease, exhibits significant vascular alternations, including blood-brain barrier (BBB) disruption, which may predispose patients to increased cardiovascular risks. This vascular dysfunction is intricately linked with the infiltration of immune cells into the central nervous system (CNS), which plays a significant role in perpetuating neuroinflammation. Additionally, oxidative stress serves not only as a byproduct of inflammatory processes but also as an active contributor to neural damage. The synthesis of these multifaceted aspects highlights the importance of understanding their cumulative impact on MS progression. This review reveals that the triad of vascular damage, chronic inflammation, and oxidative imbalance may be considered interdependent processes that exacerbate each other, underscoring the need for holistic and multi-targeted therapeutic approaches in MS management. There is a necessity for reevaluating MS treatment strategies to encompass these overlapping pathologies, offering insights for future research and potential therapeutic interventions. Whole-body cryotherapy (WBCT) emerges as one of the potential avenues for holistic MS management approaches which may alleviate the triad of MS progression factors in multiple ways.

Whole-body cryotherapy in orthopaedics: current concepts.

The use of whole-body cryotherapy (WBC) for musculoskeletal ailments is growing. WBC, involving brief exposure to extremely low temperatures, is increasingly used for its analgesic, anti-inflammatory, and antioxidant effects. The paper examines the physiological impacts of WBC on cardiovascular, musculoskeletal, hematologic, hormonal, and metabolic systems. Specific orthopaedic applications discussed include its role in the management of fractures, osteoarthritis, osteonecrosis of the femoral head, osteomyelitis, adhesive capsulitis, tendinopathies, rheumatic pathologies, chronic pain syndromes, and fibromyalgia. The study also highlights the benefits and drawbacks of WBC, including its potential to improve athletic performance, recovery, mood, and well-being, while noting risks like frostbite and impaired muscle strength. Clinical evidence from various studies is evaluated, revealing a spectrum of outcomes. For instance, WBC shows promise in enhancing bone health in athletes and providing relief in osteoarthritis and fibromyalgia patients. However, evidence for its efficacy in conditions like chronic pain syndromes and osteomyelitis is less robust. The paper underscores the need for further research to establish standardised protocols and understand long-term effects. While WBC offers significant benefits in orthopaedics, understanding its limitations and potential risks is crucial for its safe and effective clinical application.

Photodynamic Therapy Combined with Liquid Nitrogen Cryotherapy and Curettage for the Treatment of Recalcitrant Periungual and Subungual Warts: Clinical Experience and Literature Review.

Warts are caused by human papillomavirus (HPV) infection and can involve multiple parts of skin and mucosa, of which periungual and subungual warts are the most difficult to treat. Periungual or subungual wart is verruca vulgaris growing around or under the fingernail, destroying and deforming the nail and nail bed. Currently, liquid nitrogen cryotherapy and CO2 laser are often used for the treatment. Clinically, few doctors routinely use photodynamic therapy (PDT) to treat viral warts. We used PDT combined with liquid nitrogen cryotherapy and curettage to successfully treat a case of intractable periungual and subungual warts.

Isolation of the superior vena cava by ultra-low temperature cryoablation.

A patient with shocks from his ICD related to AF underwent redo ablation. The only identifiable target was the superior vena cava. This was isolated using ultra-low cryotherapy, eliminating episodes of AF.

Effects of an Early Exercise Program with Cryotherapy on Range of Motion, Pain, Swelling, and Gait in Patients with Total Knee Arthroplasty: A Randomized Controlled Trial.

Background: This study aimed to investigate the effects of cryotherapy on range of motion, pain, swelling, and gait in patients who underwent total knee arthroplasty. Methods: Forty-three patients who underwent TKA (total knee arthroplasty) and met the inclusion criteria were randomly divided into two groups. The experimental (n = 21) and control (n = 22) groups underwent cryotherapy and non-cryotherapy treatments, respectively, six times a week for two weeks, and once each before and after exercise for 3 min. Both groups followed a similar initial rehabilitation exercise program using a continuous passive motion device. Results: The results showed a significant difference in knee flexion range of motion, pain, edema, and 10 MWT comparisons from pre- to post-test (p < 0.001). The above values were also significantly different in the comparison between the two groups (p < 0.05). Conclusions: Therefore, this study confirmed that an initial rehabilitation exercise program accompanied by cryotherapy could be an effective intervention method for range of motion, pain, edema, and walking in patients undergoing total knee arthroplasty.

High-density "APLE" Mapping-Activation, Propagation, Low Voltage, and Electrogram Evaluation with the HD Grid for Atrioventricular Nodal Re-entry Tachycardia Ablation.

This is the first case series to evaluate high-density mapping of the triangle of Koch (TOK) using the HD Grid to guide slow-pathway ablation integrating activation, propagation (with wave collision), low-voltage signals, and atrial electrogram appearance. We will describe our technique and the results in this case series. Using three-dimensional mapping and the HD Grid, patients underwent high-density voltage mapping of the TOK. Ablation site selection was based on properties during sinus rhythm with late activation, at or above the propagation wave collision, over low voltage, and with appropriate electrogram appearance. Five patients underwent mapping of the slow pathway using the HD Grid. Their median age was 14 years, their median weight was 54.1 kg, and their median height was 161.5 cm. The TOK was mapped with the HD Grid for a median of 3 min. The procedure was successful in all patients using this technique. The median lesion number to the site of success was 3, with a median total number of cryotherapy lesions of 11. No radiation was used. There were no recurrences. Using activation, propagation wave, low voltage, and electrogram appearance when mapping for slow-pathway localization and ablation with the HD Grid can be successful, results in high-density maps, and is relatively faster.

In vivo study of porous NiTi cryotweezers for bone tissue cryotherapy.

This study examined the effects of liquid nitrogen vapor on osteogenesis in the rabbit femur. Cryotweezers made of porous nickel titanium alloy (nitinol or NiTi) obtained by self-propagating high temperature synthesis were used in this experiment. The porous structure of the cryotweezers allows them to hold up to 10 g of liquid nitrogen after being immersed for 2 min, which completely evaporates after 160 s. To study the effects of liquid nitrogen evaporation on osteogenesis, a rabbit femur was perforated. The formed holes were subjected to cryotherapy with varying exposure times. It was found that a 3 s exposure time stimulates osteogenesis, which was manifested in a greater number of osteoblasts in the regenerate compared to the control sample without liquid nitrogen. It was observed that increasing the exposure to 6, 9 or 12 s had a destructive effect, to varying degrees. The most severe damage was exerted by a 12 s exposure, which resulted in the formation of osteonecrosis areas. In the samples exposed to 6 and 9 s of cryotherapy, destruction of the cytoplasm of osteocytes and osteoclasts was observed.

Comparing the efficacy of fluconazole and cryotherapy Versus cryotherapy alone on treating cutaneous leishmaniasis: a triple-blind randomized clinical trial.

OBJECTIVE: Cutaneous Leishmaniasis (CL) is one of the highly prevalent endemic diseases in the Middle East. The disease is a complex skin infection imposing a heavy burden on many developing countries. This study aimed to evaluate the impact of adding oral fluconazole to topical cryotherapy on the treatment efficacy and time to achieve complete recovery of CL lesions. METHOD: This triple-blind randomized clinical trial included 52 participants with CL. Participants were allocated to receive either weekly cryotherapy with liquid nitrogen and oral fluconazole at a dose of 6 mg/kg daily at a maximum of 400 mg for 6 weeks as the interventional arm or weekly cryotherapy with liquid nitrogen plus the placebo for the same period of 6 weeks as the control arm. RESULTS: Fifty-two eligible participants enrolled the study, with a CL lesion count of 1 to 8 (mean 1.96), and served as the interventional (n = 28) and control (n = 24) arms. The trend of the mean surface area of the lesions was significantly decreasing in both arms (P < 0.001), with no statistically significant difference between arms (P = 0.133) or all assessed time point pairwise comparisons (P > 0.05). There was no significant difference between the treatment arms in terms of the end-point recovery status (P = 0.491) or the frequency of post-treatment secretion (P = 0.437). No adverse effect was observed. CONCLUSION: Despite a slightly higher reduction in the lesion surface in the cryotherapy and fluconazole treatment arm, the addition of fluconazole did not provide statistically significant therapeutic value to cryotherapy in the treatment of CL. However, with adjustment for the initial lesion size, the efficacy of the regimen in the interventional arm was more pronounced, though it was still insignificant.

Cold-Responsive Hyaluronated Upconversion Nanoplatform for Transdermal Cryo-Photodynamic Cancer Therapy.

Cryotherapy leverages controlled freezing temperature interventions to engender a cascade of tumor-suppressing effects. However, its bottleneck lies in the standalone ineffectiveness. A promising strategy is using nanoparticle therapeutics to augment the efficacy of cryotherapy. Here, a cold-responsive nanoplatform composed of upconversion nanoparticles coated with silica - chlorin e6 - hyaluronic acid (UCNPs@SiO2 -Ce6-HA) is designed. This nanoplatform is employed to integrate cryotherapy with photodynamic therapy (PDT) in order to improve skin cancer treatment efficacy in a synergistic manner. The cryotherapy appeared to enhance the upconversion brightness by suppressing the thermal quenching. The low-temperature treatment afforded a 2.45-fold enhancement in the luminescence of UCNPs and a 3.15-fold increase in the photodynamic efficacy of UCNPs@SiO2 -Ce6-HA nanoplatforms. Ex vivo tests with porcine skins and the subsequent validation in mouse tumor tissues revealed the effective HA-mediated transdermal delivery of designed nanoplatforms to deep tumor tissues. After transdermal delivery, in vivo photodynamic therapy using the UCNPs@SiO2 -Ce6-HA nanoplatforms resulted in the optimized efficacy of 79% in combination with cryotherapy. These findings underscore the Cryo-PDT as a truly promising integrated treatment paradigm and warrant further exploring the synergistic interplay between cryotherapy and PDT with bright upconversion to unlock their full potential in cancer therapy.

Effects of an ice roller on chronic kidney disease-associated pruritus in patients receiving haemodialysis.

BACKGROUND: Chronic kidney disease-associated pruritus is a distressing symptom and has a far-reaching impact on patients' sleep and quality of life for most patients receiving haemodialysis. Traditional therapies have limited effectiveness. OBJECTIVES: This study aimed to invent a self-operated ice roller and evaluate its efficacy in relieving pruritus, sleep quality, and quality of life. DESIGN: This study was experimental with a two-arm parallel group design. PARTICIPANTS: A convenient sampling method was used to recruit 60 patients receiving haemodialysis who reported pruritus (5D-Itch Scale score >5) lasting over 4 weeks in Taiwan. The participants were randomly assigned to one of two groups: the intervention group used an ice roller for 7 days, while the control group received no anti-pruritus treatment. MEASUREMENTS: This study was experimental with a two-arm parallel group design. The measurement instruments included the 5D-Itch Scale, Pittsburgh Sleep Quality Index and WHOQOL-BREF-Taiwan Version. The analysis of covariance, chi-square, Independent t tests, and partial Eta2 (η2 p) were used to analyse the data. RESULTS: The participants' mean age was 62.77 years. Application of the ice roller significantly decreased overall pruritus (p < .05; η2 p = .09) and distribution of pruritus-associated bodily parts (p = .03; η2 p = .08). There were no statistically significant differences in sleep quality and related indicators between the experimental and control groups at the study endpoint. Regarding quality of life, only the social relationship domain significantly differed between the two groups (p = .02; η2 p = .08). CONCLUSIONS: The ice roller can decrease pruritus and its distribution in patients receiving haemodialysis, serving as an adjunct therapy alongside conventional anti-pruritus treatments.

The Transatlantic Recommendations for Prostate Gland Evaluation with Magnetic Resonance Imaging After Focal Therapy (TARGET): A Systematic Review and International Consensus Recommendations.

BACKGROUND AND OBJECTIVE: Magnetic resonance imaging (MRI) can detect recurrences after focal therapy for prostate cancer but there is no robust guidance regarding its use. Our objective was to produce consensus recommendations on MRI acquisition, interpretation, and reporting after focal therapy. METHODS: A systematic review was performed in July 2022 to develop consensus statements. A two-round consensus exercise was then performed, with a consensus meeting in January 2023, during which 329 statements were scored by 23 panellists from Europe and North America spanning urology, radiology, and pathology with experience across eight focal therapy modalities. Using RAND Corporation/University of California-Los Angeles methodology, the Transatlantic Recommendations for Prostate Gland Evaluation with MRI after Focal Therapy (TARGET) were based on consensus for statements scored with agreement or disagreement. KEY FINDINGS AND LIMITATIONS: In total, 73 studies were included in the review. All 20 studies (100%) reporting suspicious imaging features cited focal contrast enhancement as suspicious for cancer recurrence. Of 31 studies reporting MRI assessment criteria, the Prostate Imaging-Reporting and Data System (PI-RADS) score was the scheme used most often (20 studies; 65%), followed by a 5-point Likert score (six studies; 19%). For the consensus exercise, consensus for statements scored with agreement or disagreement increased from 227 of 295 statements (76.9%) in round one to 270 of 329 statements (82.1%) in round two. Key recommendations include performing routine MRI at 12 mo using a multiparametric protocol compliant with PI-RADS version 2.1 standards. PI-RADS category scores for assessing recurrence within the ablation zone should be avoided. An alternative 5-point scoring system is presented that includes a major dynamic contrast enhancement (DCE) sequence and joint minor diffusion-weighted imaging and T2-weighted sequences. For the DCE sequence, focal nodular strong early enhancement was the most suspicious imaging finding. A structured minimum reporting data set and minimum reporting standards for studies detailing MRI data after focal therapy are presented. CONCLUSIONS AND CLINICAL IMPLICATIONS: The TARGET consensus recommendations may improve MRI acquisition, interpretation, and reporting after focal therapy for prostate cancer and provide minimum standards for study reporting. PATIENT SUMMARY: Magnetic resonance imaging (MRI) scans can detect recurrent of prostate cancer after focal treatments, but there is a lack of guidance on MRI use for this purpose. We report new expert recommendations that may improve practice.

Effects of post-exercise cold-water immersion on performance and perceptive outcomes of competitive adolescent swimmers.

PURPOSE: To evaluate the effects of repeated use of cold-water immersion (CWI) during a training week on performance and perceptive outcomes in competitive adolescent swimmers. METHODS: This randomized-crossover study included 20 athletes, who received each intervention [CWI (14 ± 1 °C), thermoneutral water immersion (TWI) (27 ± 1 °C) as placebo, and passive recovery (PAS)] three times a week between the land-based resistance training and swim training. The interventions were performed in a randomized order with a 1-week wash-out period. We tested athletes before and after each intervention week regarding swim (100 m freestyle sprints) and functional performance (flexibility, upper and lower body power, and shoulder proprioception). We monitored athlete's perceptions (well-being, heaviness, tiredness, discomfort and pain) during testing sessions using a 5-item questionnaire. Athlete preferences regarding the interventions were assessed at the end of the study. We used generalized linear mixed models and generalized estimating equations for continuous and categorical variables, respectively (intervention x time). RESULTS: We found a time effect for swim performance (p = .01) in which, regardless the intervention, all athletes improved sprint time at post-intervention compared to baseline. There was an intervention effect for pain (p = .04) and tiredness (p = .04), but with no significant post-hoc comparisons. We found no significant effects for other outcomes. All athletes reported a preference for CWI or TWI in relation to PAS. CONCLUSION: The repeated use of CWI throughout a training week did not impact functional or swim performance outcomes of competitive adolescent swimmers. Perceptive outcomes were also similar across interventions; however, athletes indicated a preference for both CWI and TWI.

Could tranexamic acid be a suitable alternative to cryotherapy for symptomatic cervical ectopy? Results from a randomized clinical trial.

OBJECTIVE: Cervical ectropion occurs due to the eversion of the endocervix that exposes glandular cells to the vaginal milieu. The aim of the present study was to evaluate and compare the clinical efficacy of effervescent vaginal tablets of tranexamic acid and cryotherapy in women with symptomatic cervical ectopy. METHODS: The current randomized clinical trial was conducted on 92 samples of women with cervical erosive ectropion from March 20, 2022 to August 27, 2022. Participants were divided into two groups; the intervention group (n = 46) was treated with a 400 mg effervescent vaginal tablet of tranexamic acid and the control group (n = 46) underwent cryotherapy. All the patients were requested to visit weekly in the first month and then monthly for the next 3 months, and the outcomes encompass improvement of symptoms (leukorrhea, dyspareunia, pelvic pain, post-coital bleeding, and suprapubic pain) and cervical erosive ectropion view were monitored based on repeated examinations. RESULTS: In this study, no statistically significant difference was observed in cure rate of symptoms between study groups (P value > 0.05). Women in both the tranexamic acid and cryotherapy groups reported significant improvements in dyspareunia (34 [75%] vs 31 [67%]), pelvic pain (34 [75%] vs 34 [74%]), post-coital bleeding (37 [81%] vs 31 [67%]), leukorrhea (36 [78%] vs 36 [78%]), suprapubic pain (32 [71%] vs 33 [73%]) disappearance of cervical ectropion tranexamic acid (40 [86%], vs 39 [84%]). CONCLUSION: Our findings highlighted the equal effect of tranexamic acid and cryotherapy for treating cervical ectropion. Due to the ease of use, availability, and fewer side effects of tranexamic acid, it can be a suitable alternative to cryotherapy. TRIAL REGISTRATION: IRCT20220115053719N1. The name of the registry: Iranian Registry of Clinical Trials. URL of registration: https://en.irct.ir/trial/61483.

The Healthspan Project: A Retrospective Pilot of Biomarkers and Biometric Outcomes after a 6-Month Multi-Modal Wellness Intervention.

Wellness-centric proactive healthcare is increasingly sought after, with individuals frequently embracing complementary modalities to achieve this goal. In this six-month study, healthy adult participants (n = 25) received specific therapies, including whole-body cryotherapy, infrared sauna, and photobiomodulation, along with guidance on physical activity, diet, and alcohol intake. Serum biomarkers were measured for all participants, while a subset also received biometric assessments for body composition (n = 10) and heart rate variability (n = 7). Over the course of the study (mean (SD) follow-up days = 174 (130)), participants exhibited significant improvements in health. LDL cholesterol (-9.77 (15.43) md/dL) and hsCRP (-1.75 (2.66) mg/L) decreased significantly (p < 0.05). HbA1c increased slightly (p < 0.05), but the effect size was small (0.12 (0.13)%). The body composition subset lost overall body weight (-3.29 (3.75) kg), primarily body fat, while preserving lean muscle mass (p < 0.05). Heart rate variability increased for those with existing cardiovascular risk factors (p < 0.05). In conclusion, participation in the multimodal Healthspan protocol is associated with substantial improvements in health-related biomarkers and biometrics.

Nadir prostate-specific antigen after salvage cryotherapy as a potential prognostic factor for oncologic outcomes.

PURPOSE: To report oncologic outcomes of patients undergoing salvage cryotherapy (SCT) for local recurrence of prostate cancer (PCa) and to establish a nadir PSA (nPSA) value that best defines long-term oncologic success. METHODS: Retrospective study of men who underwent SCT for local recurrence of PCa between 2008 and 2020. SCT was performed in men with biochemical recurrence (BCR), after primary treatment and with biopsy-proven PCa local recurrence. Survival analysis with Kaplan-Meier and Cox models was performed. We determined the optimal cutoff nPSA value after SCT that best classifies patients depending on prognosis. RESULTS: Seventy-seven men who underwent SCT were included. Survival analysis showed a 5-year biochemical recurrence-free survival (BRFS), androgen deprivation therapy-free survival (AFS), and metastasis-free survival (MFS) after SCT of 48.4%, 62% and 81.3% respectively. On multivariable analysis for perioperative variables associated with BCR, initial ISUP, pre-SCT PSA, pre-SCT prostate volume and post-SCT nPSA emerged as variables associated with BCR. The cutoff analysis revealed an nPSA < 0.5 ng/ml to be the optimal threshold that best defines success after SCT. 5-year BRFS for patients achieving an nPSA < 0.5 vs nPSA ≥ 0.5 was 64% and 9.5% respectively (p < 0.001). 5-year AFS for men with nPSA < 0.5 vs ≥ 0.5 was 81.2% and 12.2% (p < 0.001). Improved 5-year MFS for patients who achieved nPSA < 0.5 was also obtained (89.6% vs 60%, p = 0.003). CONCLUSION: SCT is a feasible rescue alternative for the local recurrence of PCa. Achieving an nPSA < 0.5 ng/ml after SCT is associated with higher long-term BRFS, AFS and MFS rates.

Bronchoscopy-guided Cryotherapy for Airway Obstruction from Bronchial Cast.

The application of cryotherapy in the extraction of airway blood clots has gained increased precedence over Fogarty catheter and biopsy forceps. The cryoprobe, passed through a flexible bronchoscope, adheres and aids in the removal of foreign body through cryoadhesion within minutes. Besides blood clots, this method was found to be extremely efficient in removing different kinds of foreign bodies including food particles like peanuts, pills, and inspissated mucus.

Whole Body Cryostimulation: A New Adjuvant Treatment in Central Sensitization Syndromes? An Expert Opinion.

Central sensitisation is defined as a multifactorial etiopathogenetic condition involving an increase in the reactivity of nociceptive neurons and alterations in pain transmission and perception in the central nervous system. Patients may present with widespread chronic pain, fatigue, sleep disturbance, dizziness, psychological (e.g., depression, anxiety, and anger) and social impairment. Pain can be spontaneous in onset and persistence, characterised by an exaggerated response and spread beyond the site of origin, and sometimes triggered by a non-painful stimulus. Whole-body cryostimulation (WBC) could be an adjuvant therapy in the management of this type of pain because of its global anti-inflammatory effect, changes in cytokines and hormone secretion, reduction in nerve conduction velocity, autonomic modulation, and release of neurotransmitters involved in the pain pathway. In several conditions (e.g., fibromyalgia, rheumatoid arthritis, and chronic musculoskeletal pain), WBC affects physical performance, pain perception, and psychological aspects. Given its multiple targets and effects at different organs and levels, WBC appears to be a versatile adjuvant treatment for a wide range of conditions of rehabilitation interest. Further research is needed to fully understand the mechanisms of analgesic effect and potential actions on pain pathways, as well as to study long-term effects and potential uses in other chronic pain conditions.

Modified technique improves efficacy for in-office posterior nasal nerve ablation.

Objectives: Posterior nasal nerve (PNN) ablation is a minimally invasive treatment option for patients with chronic rhinitis. Recent evidence shows that parasympathetic innervation of the nasal cavity is more extensive and there are many fibers posterior to the lateral attachment of the middle turbinate. We describe a modified ablative technique that targets the extensive innervation of the posterior nasal nerves. Methods: Description of the technique and retrospective cohort analysis. In addition to the traditional radiofrequency and cryoablation targets, three additional treatment sites posterior to the middle turbinate were targeted using radiofrequency ablation, as well as one focused treatment posteroinferior to the middle turbinate attachment using cryotherapy ablation. The primary outcome collected was a 30% improvement in overall rhinitis symptoms. Results: Forty-five patients received treatment and completed 3-month follow-up using the modified technique for radiofrequency and cryotherapy PNN ablation. Previously, our institution documented a 64.5% responder rate at 3 months. After introducing the modified technique, the response rate at 3 months significantly improved (64.5% vs. 91.1%, p = .004). Conclusions: This report suggests improved efficacy with implementation of the modified technique for in-office PNN ablation. Given the extensive nature of the post-ganglionic parasympathetic fibers of the nasal cavity which often emerge posterior to the middle turbinate attachment, a modified technique to target these branches should be considered. Prospective randomized studies comparing this modified technique to the traditional technique are needed. Level of Evidence: III.