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.

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.

The Effect of a Combination of Vibration and External Cold on Pain Caused during Vaccine Injection in Infants: A Randomized Clinical Trial.

Aim: This study was conducted to determine the effect of combining vibration and external cold on pain caused by vaccine injection among six-month-old infants. Design: Randomized controlled trial. Methods: In this clinical trial, 80 eligible infants were selected from the infants referred to a health center as per the inclusion criteria. The infants were assigned to either a control group or an intervention group by block randomization. In the intervention group, a vibrating and cold device was placed above the injection site from one minute before to 15 seconds after the pentavalent vaccine injection. In the control group, no intervention was performed, and they were vaccinated according to the routine procedure. The pain status in the two groups was measured using the Modified Behavioral Pain Scale (MBPS) 15 seconds after the injection, and the crying duration was assessed from the injection of the vaccine till the end of it. Data were analyzed in SPSS 23 software using Mann-Whitney, t, Spearman, and chi-square tests. The level of significance was set to p < 0.05. Results: Most participants in the control (55%) and intervention (55%) groups were girls. Statistical data analysis of 80 infants showed that the mean pain intensity (p = 0.032) and duration of crying (p = 0.0001) in the intervention group (6.1 ± 1.8, 32.47 ± 16.78) were lower than those of the control group (7.2 ± 0.1, 51.02 ± 25.9), respectively. Conclusion: Because the intensity of pain, especially the duration of crying, was lower in the intervention group than in the control group, we may suggest that nurses use simple pain relief solutions in vaccination centers, such as a combination of vibration and cold. This trial is registered with IRCT201207157130N2.

ONYCHOLYSIS AS A COMPLICATION OF TAXANE-BASED CHEMOTHERAPY WITH CONCOMITANT CRYOTHERAPY IN BREAST CANCER PATIENTS: TWO CASE REPORTS.

Nail changes are a common side effect of taxane chemotherapy, although onycholysis is quite a rare complication the correct management of which is poorly standardized. These case reports provide a description and analysis of onycholysis, a rare but noteworthy complication observed during taxane-based chemotherapy with concomitant cryotherapy in two patients with breast cancer. Despite prophylactic measures, both cases experienced nail complications during Paclitaxel treatment, underlining the complex nature of onycholysis during taxane therapy and highlighting the critical role of nail assessment and infection screening.

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.

Assessment of Ingrown Toenails Treated with Nail Fold Cryotherapy in Adolescent Patients: An Observational Pilot Study.

BACKGROUND: Cryotherapy reduces pain by making some reversible functional changes in peripheral nerves. It has also been reported to have a positive effect on the regression of inflammation and granulation tissue. Few studies have evaluated the efficacy and safety of nail fold cryotherapy in ingrown toenails (IGTN) in adults, and there are no studies in the pediatric population. We aimed to evaluate the clinical efficacy of cryotherapy applied to the nail fold in juvenile IGTN. METHODS: This study was conducted in adolescent patients aged 12 to 16 years with unilateral juvenile IGTN. Liquid nitrogen was sprayed into the nail fold for 10 to 15 seconds with a double freeze-thaw cycle. The effectiveness of cryotherapy was interpreted by the clinician's decision, the improvement in visual analogue scale score, Children's Dermatology Life Quality Index score, and granulation tissue. RESULTS: According to the physician, good efficacy was achieved in 91.7% of patients (n = 22 of 24). We found that 54.5% of them (n = 12 of 22) were still in remission after 6 months. Rates of complete regression in granulation tissue were pronouncedly less in sizes larger than 5 mm (≤5 mm, 55.6%; >5 mm, 16.7%). However, adequate symptomatic relief was observed in 83.3% of stage 3 patients, even if complete granulation tissue response was not achieved yet. Significant improvements in visual analogue scale and the Children's Dermatology Life Quality Index scores were observed after cryotherapy (P < .05). CONCLUSIONS: Nail fold cryotherapy is a useful alternative among conservative methods because of its rapid and high efficiency (91.7%), especially in mild to moderate cases, despite the high recurrence rates (45.5%) in juvenile IGTN.

[Cryotherapy combined with local spraying of isoniazid for the treatment of nasopharyngeal tuberculosis: a case report].

Nasopharyngeal tuberculosis refers to the tuberculosis in the nasopharynx, which is mainly treated with systemic chemotherapy with anti-tuberculosis drugs. Here, we reported a case of nasopharyngeal tuberculosis treated by cryosurgery combined with local spraying of isoniazid on the basis of systemic chemotherapy with anti-tuberculosis drugs. By reviewing the case data and relevant literature, we understood the clinical manifestations, diagnosis and differential diagnosis of the disease, improved everyone's understanding of the disease, and proposed a new method of cryosurgery combined with local spraying of isoniazid for the treatment of nasopharyngeal tuberculosis for clinical discussion.

Pre-emptive ice pack cryotherapy for reducing pain caused by long-acting deltoid injectable antipsychotic treatment: A single-center open-label study.

PURPOSE: This empirical study aims to investigate the efficacy of pre-emptive cryotherapy in reducing pain that is caused by the deltoid intramuscular (IM) injection of long-acting injectable (LAI) antipsychotics in clinical settings. PATIENTS AND METHODS: This study included 29 outpatients receiving LAI antipsychotic treatment. The evaluations of pain during (1) the usual procedure (control), (2) pre-emptive use of ice pack cryotherapy (pre-cooling), and (3) pre-emptive use of a room-temperature ice pack (pre-touching) were conducted using a numerical rating scale (NRS) for comparison. All patients were administered with LAI antipsychotics via deltoid IM. Furthermore, the results of the Positive and Negative Symptom Scale (PANSS), clinical global impressions (CGI) scale, and Global Assessment of Functioning (GAF) scale that were administered during the control procedure were evaluated. RESULTS: The median NRS pain scores during the IM injection of LAI antipsychotics were 4.0 (3.0-5.0), 2.0 (1.0-3.0), and 3.0 (2.5-6.0) for the control, pre-cooling, and pre-touching conditions, indicating a significant difference (p = 6.0 × 10-6). The NRS pain scores for the pre-cooling condition were significantly lower than those for the control and pre-touching conditions (p = 2.5 × 10-5 and 6.7 × 10-5, respectively). No significant correlation was observed between the NRS pain scores for the control condition and the PANSS, CGI scale, or GAF scale scores. Furthermore, no adverse events were recorded during the study period. CONCLUSION: Pain during the deltoid IM injection of LAI antipsychotics was found to be reduced by pre-emptive skin cooling. To date, this is the first study to confirm the effectiveness of pre-emptive cryotherapy for relieving such pain in clinical situations.

Randomized controlled trial of compressive cryotherapy versus standard cryotherapy after total knee arthroplasty: pain, swelling, range of motion and functional recovery.

BACKGROUND: After total knee arthroplasty (TKA), patients have limited knee range of motion (ROM), trophic changes and pain. Cryotherapy and compression are recommended in the literature, but no study has shown that cryotherapy and compression combined leads to better results than cryotherapy alone. The primary objective was to compare knee ROM after 21 days of rehabilitation post-TKA between patients who underwent rehabilitation with compressive cryotherapy with those who had cryotherapy alone. The secondary objectives were to compare other trophic, pain and functional outcomes. METHODS: Forty patients were randomized into two groups: Standard Cryotherapy (SC = 20, median age 77 years), which applied cold packs along with their rehabilitation; and Compressive Cryotherapy (CC = 20, median age 76 years), which received cold compression. Knee joint's passive and active ROM (primary outcome) were measured with a goniometer. Knee's circumference, fluctuation test, pain at rest and during activity, 6-minute walking test (6MWT) and KOOS questionnaire were secondary outcomes. The groups were compared on D1 (baseline) and D21 of rehabilitation. A survival analysis has compared the groups on D1, D8, D15, D21. RESULTS: All subjects had a significant improvement in all the parameters on D21 relative to D1 (p < .05), except for pain at rest (p = .065 for CC and p = .052 for SC). On D21, the CC group had a significantly larger improvement in the joint effusion (p = .002), pain during activity (p = .005), 6MWT (p = .018) and KOOS (p = .004) than the SC group. Based on the survival analysis, the CC group had significantly faster improvement in the joint ROM (p = .011 for flexion and p = .038 for extension) and knee circumference (p = .013) than the SC group. CONCLUSIONS: Both cryotherapy methods improved joint ROM, trophic changes, pain and function. Adding dynamic compression to a cryotherapy protocol provided further benefits: a significantly faster improvement in passive knee flexion ROM, a greater reduction of swelling, and pain during activity. Similarly, walking distance and KOOS questionnaire were significantly better for CC. TRIALS REGISTRATION: The study was registered in the ClinicalTrials.gov database on 14/09/2023 (identifier: NCT06037824).

Cold urticaria as a complication of cryotherapy in the treatment of viral warts.

Cryotherapy with liquid nitrogen has been established as the first-line treatment for pediatric patients with viral warts. Cold-induced urticaria (CU) is a rare skin reaction triggered by cold stimuli. We present the case of a pediatric patient with viral warts who developed CU after receiving cryotherapy.

Effects of Two Different Cold Application Methods After Rhinoplasty: A Randomized Clinical Trial.

The aim of this prospective, randomized controlled clinical trial was to evaluate the effects of two methods of cold application on eye ecchymosis, periorbital edema, pain around the eyes and face, and patient comfort in postoperative rhinoplasty patients. Patients were randomly divided and evaluated in two groups: an ice in disposable latex gloves (IDLG) group and a cooling gel eye mask (CGEM) group. We used the CONSORT checklist to report the study. There were no significant differences between the groups in terms of age, gender, preoperative blood pressure, respiration, fever status, oxygen saturation, or postoperative vital signs. Patients in the IDLG group had significantly higher scores for pain around the eyes, facial pain, and periorbital edema on the first postoperative day, and significantly higher facial edema scores during the first postoperative hour (p ≤ .05). Patients in the CGEM group reported that they slept more comfortably (p ≤ .05). The results of our study showed that CGEMs reduce pain, periorbital edema, and facial edema after rhinoplasty.

The impact of text message reminders on cryotherapy uptake among women testing positive for HPV in western Kenya: a prospective cohort study.

BACKGROUND: Mobile health (mHealth) has become an increasingly popular strategy to improve healthcare delivery and health outcomes. Communicating results and health education via text may facilitate program planning and promote better engagement in care for women undergoing human papillomavirus (HPV) screening. We sought to develop and evaluate an mHealth strategy with enhanced text messaging to improve follow-up throughout the cervical cancer screening cascade. METHODS: Women aged 25-65 participated in HPV testing in six community health campaigns (CHCs) in western Kenya as part of a single arm of a cluster-randomized trial. Women received their HPV results via text message, phone call, or home visit. Those who opted for text in the first four communities received "standard" texts. After completing the fourth CHC, we conducted two semi-structured focus group discussions with women to develop an "enhanced" text strategy, including modifying the content, number, and timing of texts, for the subsequent two communities. We compared the overall receipt of results and follow-up for treatment evaluation among women in standard and enhanced text groups. RESULTS: Among 2368 women who were screened in the first four communities, 566 (23.9%) received results via text, 1170 (49.4%) via phone call, and 632 (26.7%) via home visit. In the communities where enhanced text notification was offered, 264 of the 935 screened women (28.2%) opted for text, 474 (51.2%) opted for phone call, and 192 (20.5%) for home visit. Among 555 women (16.8%) who tested HPV-positive, 257 (46.3%) accessed treatment, with no difference in treatment uptake between the standard text group (48/90, 53.3%) and the enhanced text group (22/41, 53.7%). More women in the enhanced text group had prior cervical cancer screening (25.8% vs. 18.4%; p < 0.05) and reported living with HIV (32.6% vs. 20.2%; p < 0.001) than those in the standard text group. CONCLUSIONS: Modifying the content and number of texts as an enhanced text messaging strategy was not sufficient to increase follow-up in an HPV-based cervical cancer screening program in western Kenya. A one-size approach to mHealth delivery does not meet the needs of all women in this region. More comprehensive programs are needed to improve linkage to care to further reduce structural and logistical barriers to cervical cancer treatment.

Effects of 6 weeks of cryotherapy plus compression therapy after total or unicompartmental knee arthroplasty: protocol for a single-centre, single-blind randomised controlled trial.

INTRODUCTION: Effective rehabilitation after total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA) is often impeded by pain and swelling. Beneficial short-term effects in terms of pain and opioid use after a short period of cryotherapy (±compression therapy) have been demonstrated. The effectiveness of a longer intervention period on longer-term postoperative outcomes is unclear. This study aims to assess the effects of 6 weeks of cryotherapy plus compression therapy on pain, functioning and patient satisfaction after TKA or UKA. METHODS AND ANALYSIS: A single-centre, single-blind randomised controlled trial will be conducted at a teaching hospital in the Netherlands. Patients over age 18 with end-stage osteoarthritis planned for a TKA or UKA are eligible; 104 UKA and 104 TKA patients will be included. Both groups will be randomly allocated (1:1) into an intervention group receiving 6 weeks of cryotherapy plus compression therapy (commencing after discharge from hospital) or a control group (usual care). The primary endpoint is perceived pain at rest at 6 weeks postoperatively. Secondary outcomes include compliance with cold protocol, pain at rest during the first six postoperative weeks and at 6 and 12 months postoperatively, pain on weight bearing, opioid use, functioning, patient satisfaction and complications. ETHICS AND DISSEMINATION: The local medical ethics committee MEC-U approved the study protocol (R22.095/NL-number NL81956.100.22). The study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice regulations, and personal data will be handled in agreement with the Dutch Personal Data Protection Act (AGV). Written informed consent will be obtained prior to performing any of the study procedures. We will disseminate study results through multiple peer-reviewed publications and through conference presentations. TRIAL REGISTRATION NUMBER: NCT05572359.

Salvage cryotherapy for prostate cancer.

BACKGROUND: Most men diagnosed with prostate cancer will be candidates for active treatment and 20 to 50% of patients treated with organ preserving strategies recur within the prostate. Optimal treatment of recurrence is controversial. Prostate cryosurgery has been increasingly used as primary, recurrence and focal treatment for prostate cancer. METHODS: We analysed 55 patients submitted to cryotherapy as salvage treatment after recurrence. RESULTS: Study population presented with a mean age of 70.9 ± 6.2 years, mean initial PSA of 7.6 ng/ml and average prostate volume by ultrasound of 43.2 ± 14.7 grams. Mean follow-up was of 18.0 months. Biochemical free survival at one year of follow-up was of 85%. CONCLUSIONS: Cryotherapy can be an effective and safe treatment for recurrence after primary curative treatment failure.

Autoinoculation Therapy for the Treatment of Widespread Cutaneous Warts.

BACKGROUND: Cutaneous warts are common lesions that are often unresponsive to various therapeutic modalities. OBJECTIVE: To assess the role of autoinoculation therapy in the treatment of widespread cutaneous warts. MATERIALS AND METHODS: This interventional study included patients with widespread skin warts who did not respond to conventional treatments. Two methods were used to perform the autoinoculation therapy. The first procedure was performed by obtaining a small piece of the wart and inoculating it into a subcutaneous pocket. The second method was developed by the investigator and was performed by inserting a needle into the center of the wart toward the nearby subcutaneous tissue, with multiple forward and backward movements in several directions around the lesion. RESULTS: The prospective study included 23 patients. The illness duration ranged from 3 months to 5 years. Autoinoculation interventions revealed full recovery of all warts in 20 cases (87%) within 20 to 90 days (mean: 40.7 days). CONCLUSION: Autoinoculation procedures demonstrated effectiveness, less cost, lesser pain, less invasiveness, without leaving skin scars in comparison with other conventional therapies.

A randomised crossover trial of five cryocompression devices' ability to reduce skin temperature of the knee.

BACKGROUND: The application of cold and pressure to the knee is a common part of post-operative rehabilitation. Skin temperature should be reduced to within 10-15 °C to optimise the therapeutic benefits of cryocompression. The purpose of this study was to investigate the ability of five different cryocompression devices to reduce skin temperature to within this therapeutic range. MATERIALS AND METHODS: 32 healthy adult participants (mean (SD): age 26.3 (7.9) years; BMI 24.8 (2.7) kg/m2; 20 males) were recruited for this randomised crossover study. Skin temperature was measured 20 mm distal to the patella using a k-type thermocouple every five minutes during a 30-minute treatment with one of five different cryocompression devices (Physiolab S1, GameReady, Cryo/Cuff, VPulse, and a Gel Wrap). Changes in skin temperature over time were compared to baseline within and between conditions. A subjective rating of comfort was also recorded for each device. RESULTS: The Physiolab S1 and GameReady devices caused significantly lower skin temperatures compared to the VPulse, Gel Wrap, and Cryo/Cuff after 30 minutes (p<0.05). 87-96% reported a positive comfort rating for the Physiolab S1, VPulse, Cryo/Cuff and Gel Wrap, whereas 53% of participants reported a positive comfort rating for the GameReady. CONCLUSIONS: Only the Physiolab S1 and GameReady devices reduced skin temperature of the knee to within the target range of 10-15 °C. The Physiolab S1 was reportedly more comfortable than the GameReady. Clinicians should be aware of the performance differences of different cryocompression devices to understand which is most likely to provide an effective dose of cold therapy to a joint.

Spray Cryotherapy for Benign Large Airway Stenosis: A Multicenter Retrospective Cohort Study of Safety and Practice Patterns.

BACKGROUND: Benign airway stenosis (BAS) represents a significant burden on patients, providers, and healthcare systems. Spray cryotherapy (SCT) has been proposed as an adjunctive treatment to reduce BAS recurrence. We sought to examine safety and practice variations of the latest SCT system when used for BAS. METHODS: We conducted a retrospective multicenter cohort study in seven academic institutions within the Interventional Pulmonary Outcomes Group. All patients who underwent at least one SCT session with a diagnosis of BAS at the time of procedure at these institutions were included. Demographics, procedure characteristics, and adverse events were captured through each center's procedural database and electronic health record. RESULTS: A total of 102 patients underwent 165 procedures involving SCT from 2013 to 2022. The most frequent etiology of BAS was iatrogenic (n = 36, 35%). In most cases, SCT was used prior to other standard BAS interventions (n = 125; 75%). The most frequent SCT actuation time per cycle was five seconds. Pneumothorax complicated four procedures, requiring tube thoracostomy in two. Significant post-SCT hypoxemia was noted in one case, with recovery by case conclusion and no long-term effects. There were no instances of air embolism, hemodynamic compromise, or procedural or in-hospital mortality. CONCLUSION: SCT as an adjunctive treatment for BAS was associated with a low rate of complications in this retrospective multicenter cohort study. SCT-related procedural aspects varied widely in examined cases, including actuation duration, number of actuations, and timing of actuations relative to other interventions.