IFNγ at the early stage induced after cryo-thermal therapy maintains CD4+ Th1-prone differentiation, leading to long-term antitumor immunity.

Introduction: Recently, more and more research illustrated the importance of inducing CD4+ T helper type (Th)-1 dominant immunity for the success of tumor immunotherapy. Our prior studies revealed the crucial role of CD4+ Th1 cells in orchestrating systemic and durable antitumor immunity, which contributes to the satisfactory outcomes of the novel cryo-thermal therapy in the B16F10 tumor model. However, the mechanism for maintaining the cryo-thermal therapy-mediated durable CD4+ Th1-dominant response remains uncovered. Additionally, cryo-thermal-induced early-stage CD4+ Th1-dominant T cell response showed a correlation with the favorable prognosis in patients with colorectal cancer liver metastasis (CRCLM). We hypothesized that CD4+ Th1-dominant differentiation induced during the early stage post cryo-thermal therapy would affect the balance of CD4+ subsets at the late phase. Methods: To understand the role of interferon (IFN)-γ, the major effector of Th1 subsets, in maintaining long-term CD4+ Th1-prone polarization, B16F10 melanoma model was established in this study and a monoclonal antibody was used at the early stage post cryo-thermal therapy for interferon (IFN)-γ signaling blockade, and the influence on the phenotypic and functional change of immune cells was evaluated. Results: IFNγ at the early stage after cryo-thermal therapy maintained long-lasting CD4+ Th1-prone immunity by directly controlling Th17, Tfh, and Tregs polarization, leading to the hyperactivation of Myeloid-derived suppressor cells (MDSCs) represented by abundant interleukin (IL)-1ß generation, and thereby further amplifying Th1 response. Discussion: Our finding emphasized the key role of early-phase IFNγ abundance post cryo-thermal therapy, which could be a biomarker for better prognosis after cryo-thermal therapy.

Eyebrow and Eyelash Loss in Patients With Cancer.

Though it is widely acknowledged that cancer treatments cause hair loss on the scalp, there are limited data on how they affect eyebrow and eyelash hairs. Patients with eyebrow and eyelash loss, or madarosis, seek various treatment options ranging from camouflage techniques with makeup, permanent tattoos, and prescription medications. Though not yet studied in patients with cancer-induced madarosis, techniques such as scalp cooling, cryotherapy, and topical vasoconstrictors are promising preventative options. More robust research is needed to improve both the quality and quantity of available treatment and preventative options. There is a clear need for dermatologists to play a role in supportive oncodermatology for patients who experience eyebrow and eyelash loss secondary to chemotherapy, endocrine therapies, and radiation therapy. J Drugs Dermatol. 2024;23(5):327-331. doi:10.36849/JDD.8003.

Every Picture Tells A Story: Managing Exertional Heatstroke with Rotating Ice Water Towels.

ABSTRACT: A 23-year-old woman completing her first marathon collapsed near the finish line at 4 hours 6 min with a rectal temperature of 41.8°C. She was in good health before the race with no recent illness, had completed a full training program, and was taking no medications or supplements. On the initial exam, she was unconscious with a response to painful stimulus, spontaneous breathing, rapid pulse, eyes closed, fully dilated pupils, poor muscle tone, and pale skin that was warm to touch. The medical team initiated whole-body cooling using rapidly rotating ice water towels and ice packs placed in the neck, axilla, and groin. She developed echolalia during active cooling. About 20 minutes into the cooling procedure, she "woke up," was able to answer questions coherently, and her pupils were normal size and reactive. She was discharged home with instructions to follow-up in 2 d for evaluation and blood chemistry testing.

Characterization of the role of Facebook groups for patients who use scalp cooling therapy: a survey study.

Since the emergence of scalp cooling therapy (SCT) for the prevention of chemotherapy-induced alopecia (CIA), support groups on social media platforms for interested patients have surfaced. Though there are over 20,000 active members across SCT Facebook groups, little is known about how members use this platform. A 23-question survey was posted in five scalp cooling Facebook groups, reaching 219 women. Results indicated that these Facebook groups play clear roles in providing the following: (1) a supportive community for patients, (2) instructions for SCT use, (3) advice regarding insurance coverage and reimbursement, and (4) recommendations for over-the-counter products for hair loss. Despite reported interest in hair loss products, only 5% of patients sought medical treatment from dermatologists. Due to group-specific access restrictions, private Facebook groups provide patients with a protected platform to learn more about SCT from both those with personal experience and SCT company specialists. Providers may consider recommending these online groups to interested patients during the scalp cooling counseling process. As patients with CIA express a growing interest in over-the-counter hair, eyebrow, and eyelash products, it is important for dermatologists to be aware of where their patients obtain recommendations, and further, if these recommendations have clinical evidence of efficacy.

Effect of submucosal cryotherapy compared with steroids and NSAIDs injections on Substance P and Interleukin 6 pulpal release in experimentally induced pulpal inflammation in rabbits.

OBJECTIVE: To compare the effect of submucosal cryotherapy using cold saline to dexamethasone sodium phosphate and diclofenac sodium injections on substance P and interleukin 6 release in experimentally induced pulpal inflammation in rabbits' molar teeth. METHODOLOGY: Fifteen rabbits were randomly classified into 3 groups according to the submucosal injection given: cold saline, dexamethasone sodium phosphate, and diclofenac sodium. A split-mouth design was adopted, the right mandibular molars were experimental, and the left molars served as the control without injections. Intentional pulp exposures were created and left for 6 hours to induce pulpitis. Pulpal tissue was extracted and examined for SP and IL-6 levels using ELISA. Within each group, the level of cytokines released was measured for both control and experimental groups for intragroup comparison to determine the effect of injection. The percentage reduction of each mediator was calculated compared with the control side for intergroup comparison then the correlation between SP and IL-6 levels was analyzed using Spearman's rank order correlation coefficient. Statistical analysis was performed, and the significance level was set at p<0.05. RESULTS: Submucosal cryotherapy, dexamethasone sodium phosphate, and diclofenac sodium significantly reduced SP and IL-6 pulpal release. Submucosal cryotherapy significantly reduced SP more than and IL-6 more than dexamethasone sodium phosphate and diclofenac sodium. Pulpal reduction of SP and IL-6 showed a strong positive significant correlation. CONCLUSIONS: Submucosal cryotherapy reduces the pulpal release of SP and IL-6 and could be tested as an alternative to premedication to potentiate the effect of anesthesia and control postoperative endodontic pain.

[Treatment of acute ankle distortion in footballers : Are we doing it particularly right or particularly wrong?] / Die Behandlung der akuten oberen Sprunggelenksdistorsion beim Fußballer : Machen wir es beim Profi besonders richtig oder besonders falsch?

BACKGROUND: Despite the high incidence of ankle sprains, the ideal treatment is controversial and a significant percentage of patients who have suffered an ankle sprain never fully recover. Even professional athletes are affected by this post-traumatic complication. There is strong evidence that permanent impairment after an ankle injury is often due to an inadequate rehabilitation and training program and too early return to sport. THERAPY AND REHABILITATION: Therefore, athletes should start a criteria-based rehabilitation after ankle sprain and gradually progress through the programmed activities, including e.g. cryotherapy, edema reduction, optimal load management, range of motion exercises to improve ankle dorsiflexion and digital guidance, stretching of the triceps surae with isometric exercises and strengthening of the peroneus muscles, balance and proprioception training, and bracing/taping. The fact that this is professional sport does not exempt it from consistent, stage-appropriate treatment and a cautious increase in load. However, there are a number of measures and tools that can be used in the intensive care of athletes to improve treatment and results.

Salvage prostate intensity modulated radiation therapy after cryotherapy failure.

Cryotherapy is an ablative therapy that can be used to treat localized prostate cancer. In case of recurrence, treatment options are not well-defined, and their outcomes are unknown. We therefore collected all patients treated with radiotherapy after cryotherapy for prostate cancer recurrence in Nantes (France) between 2012 and 2019. We identified ten patients. After a median follow-up of 5 years, two patients presented late grade 3 toxicities; one patient presented a grade 3 rectal hemorrhage, and one had a grade 3 hematuria. Two patients relapsed at 61 and 62 months, and three patients died of other causes. Radiotherapy to treat local prostate cancer recurrence after cryotherapy seems feasible and effective in local control. These results do not allow us to recommend this technique in current practice but are encouraging for the conduct of prospective trials.

The effect of cryotherapy on pain in patients with total knee replacement surgery: a meta-analysis.

Cryotherapy is used to reduce edema and pain after total knee replacement surgery. This study was conducted as a meta-analysis study to determine the effect of cryotherapy on pain in patients undergoing total knee arthroplasty. The words 'total knee prosthesis,' 'pain,' 'cryotherapy,' 'cold application,' and 'orthopedic surgery' were searched in Turkish and English in scientific articles in the last 20 years from Scopus, Science Direct, Google Scholar, Pubmed databases. As a result of the research, a total of 8.406 studies were identified. Funnel Plot, Rosenthal's Secure N, and Orwin's Secure N methods were used to demonstrate that the meta-analysis study was reliable and valid and to determine publication bias. The sample size of the studies included in the analysis was 1462. The total effect size was 2.929, with a lower bound of 1.641 and an upper bound of 5.223 at a 95% confidence interval. The study determined that patients who underwent cryotherapy in total knee replacement surgery had 2.9 times less pain than patients who did not undergo cryotherapy.

Age group-specific changes in keratinocyte cancer treatment rates in Australia, 2012-2021: a retrospective cohort study based on MBS claims data.

OBJECTIVES: To examine recent changes in the numbers of Medicare-subsidised keratinocyte cancer excisions, particularly for younger people exposed to primary prevention campaigns since the early 1980s. STUDY DESIGN: Retrospective cohort study; analysis of administrative data. SETTING, PARTICIPANTS: Analysis of Medicare Benefits Schedule (MBS) claims data for procedures related to the diagnosis and treatment of keratinocyte cancer in Australia, 2012-2021. MAIN OUTCOME MEASURES: Age-standardised rates for MBS-subsidised claims for first surgical squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) excisions, Mohs surgery, surgical excisions of benign lesions, skin biopsies, and cryotherapy or serial curettage of premalignant and malignant lesions, overall, and by sex, state/territory, and age group; average annual percentage change in rate for time intervals determined by joinpoint regression. RESULTS: In men, the age-standardised rate of BCC/SCC excisions increased by 1.9% (95% confidence interval [CI], 1.4-2.4%) per year during 2012-2019 (from 2931 to 3371 per 100 000 men) and then declined by 3.8% (95% CI, 0.5-7.0%) per year during 2019-2021 (to 3152 per 100 000). In women, the age-standardised rate increased by 2.2% (95% CI, 1.7-2.8%) per year during 2012-2019 (from 1798 to 2093 per 100 000 women); the decline to 1967 excisions per 100 000 women in 2021 was not statistically significant. BCC/SCC excision rates declined for men under 55 years of age (by 1.0-3.4% per year) and women under 45 years of age (by 1.7-2.3% per year). Age-standardised biopsy rates increased during 2012-2021 in all age groups (by 2.8-6.9% per year). CONCLUSIONS: Rates of MBS-subsidised treatment for keratinocyte cancers increased during 2012-2019, but BCC/SCC treatment rates declined among younger Australians, who have probably been exposed to less sunlight than earlier generations because of public health interventions and population-wide lifestyle changes related to technology use.

The effects of cold exposure (cold water immersion, whole- and partial- body cryostimulation) on cardiovascular and cardiac autonomic control responses in healthy individuals: A systematic review, meta-analysis and meta-regression.

BACKGROUND: Cryostimulation and cold-water immersion (CWI) have recently gained widespread attention due to their association with changes in cardiovascular and cardiac autonomic control responses. Therefore, the aim of the present systematic review and meta-analysis was to identify the global impact of such cold exposures on cardiovascular and cardiac autonomic activity. METHODS: Three databases (PubMed, Embase, Web-of-Science) were used. Studies were eligible for inclusion if they were conducted on healthy participants using cryostimulation and/or CWI. The outcomes included measurements of blood pressure (BP), heart rate (HR), and heart rate variability (HRV) indices: RR interval (RR), Root mean square of successive RR interval differences (RMSSD), low frequency band (LF), high frequency band (HF), and LF/HF ratio. RESULTS: Among the 27 articles included in our systematic literature review, only 24 were incorporated into the meta-analysis. Our results reveal a significant increase in HRV indices: RMSSD (Standardized mean difference (SMD) = 0.61, p < 0.001), RR (SMD = 0.77, p < 0.001), and HF (SMD = 0.46, p < 0.001), as well as significantly reduced LF (SMD = -0.41, p < 0.001) and LF/HF ratio (SMD = -0.25, p < 0.01), which persisted up to 15 min following cold exposure. Significantly decreased heart rate (SMD = -0.16, p < 0.05), accompanied by slightly increased mean BP (SMD = 0.28, p < 0.001), was also observed. These results seem to depend on individual characteristics and the cooling techniques. CONCLUSION: Our meta-analysis suggests that cryostimulation and/or CWI exposure enhance parasympathetic nervous activity. There is scarce scientific literature regarding the effect of individual characteristics on cold-induced physiological responses.

Novel cryotherapy technique for pulpotomy in mature permanent teeth with symptomatic irreversible pulpitis- a randomized controlled trial.

OBJECTIVES: To assess the effect of cryotherapy on haemostasis, post-operative pain, and the outcome of full pulpotomy performed in mature permanent teeth with symptomatic irreversible pulpitis. MATERIALS AND METHODS: The study included sixty mature permanent mandibular molar teeth with symptomatic irreversible pulpitis and no periapical rarefaction. After coronal pulp tissue amputation, teeth were randomly allocated to one of two groups (n = 30 each). In group I (conventional pulpotomy), a sterile cotton pellet moistened with 2.5% NaOCl was used for haemostasis. In group II (cryotherapy), the pulp chamber was continuously lavaged with 2.50C normal saline solution for haemostasis using an indigenous portable cryotherapy irrigation unit. Following haemostasis, the pulp was capped with mineral trioxide aggregate and the tooth was restored with resin composite. The time taken to achieve haemostasis was recorded. Preoperative and 24, 48 and 72 h postoperative pain was measured using the Numerical Rating Scale. The pulpotomy outcome was assessed at the 12-month follow-up. Data were analyzed using Fischer's exact test, two-sample t-test, two-sample Wilcoxon rank-sum test, Friedman Test, and Wilcoxon Signed Rank Test. RESULTS: The cryotherapy group achieved haemostasis in less time (p < 0.05). There was a significant pain reduction at 24 and 48 h in the cryotherapy group when compared with the conventional pulpotomy group (P < 0.005). The overall success rate of pulpotomy after 12 months was 88% (n = 22) in both study groups(p < 0.05). CONCLUSIONS: Cryotherapy application reduces postoperative pain and has no adverse effect on the outcome of pulpotomy in permanent teeth with symptomatic irreversible pulpitis. CLINICAL RELEVANCE: The cryotherapy can be incorporated in pulpotomy protocol as an adjunct to minimize post-operative pain.

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.

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.

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.

Successful treatment of Bowen's Disease in the nipple-areola complex with a combination of photodynamic therapy and cryotherapy-A case report.

Photodynamic therapy (PDT) is a non-invasive, effective treatment for superficial skin conditions, offering superior cosmetic outcomes compared with traditional therapies. Bowen's disease (BD) of the nipple-areola complex (NAC) is rare and thus, lacks a standardized treatment approach. This report details the case of a 48-year-old woman who was successfully treated for BD of the NAC using PDT. Over a follow-up period of 30 months, there was no evidence of disease recurrence, underscoring the potential of PDT as a viable treatment option for this rare manifestation of BD.

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.

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.