Exercise training during evening may disturb sleep patterns and hinder recovery process. The present study aimed to examine the effect of whole body cryotherapy (WBC) exposure after training in the evening on sleep quality and night heart rate variability (HRV). A total of 22 physically active men were randomized to undergo either WBC (3-min at -40°C, wind speed of 2.3 m s) or passive recovery (control) following an evening training consisting of 25 min of continuous running at 65% of the maximal aerobic speed (MAS) followed by intermittent running at 85% of the MAS. Each night following the training, the number of movements and HRV during sleeping time were recorded. The next morning, subjective sleep quality and perceived pain were assessed using Spiegel questionnaire and a visual analogue scale, respectively. The number of movements during the night following WBC was significantly reduced ( < 0.05) compared with the control condition. Subjective sleep quality following WBC was significantly better than the control group ( < 0.05). During the estimated slow-wave sleep (SWS), the high frequency power (HF) was higher in the WBC group than the control group ( < 0.05), and the low frequency power (LF) and the LF/HF ratio were lower than the control group ( < 0.05). Pain was significantly reduced following WBC compared to the control ( < 0.01). In conclusion, the use of 3-min WBC after training in the evening improves subjective and objective sleep quality in physically active subjects, which may be due to greater pain relief and improved parasympathetic nervous activity during the SWS period.

BACKGROUND:Monotherapy with immune checkpoint inhibitors has generally been unsuccessful in men with advanced prostate cancer. Preclinical data support the notion that cryotherapy may improve immune-mediated and anti-tumor responses. The objective of this study was to assess the safety and feasibility of whole-prostate gland cryotherapy combined with pembrolizumab and androgen deprivation in men with oligometastatic hormone-sensitive prostate cancer.

METHODS:This single-institution, pilot trial recruited 12 patients with newly diagnosed oligometastatic prostate cancer between 2015 and 2016. Patients underwent whole-prostate cryoablation combined with short-term androgen deprivation (eight months) and pembrolizumab (6 doses). The primary clinical endpoints were the number of patients with a PSA level of<0.6 ng/mL at one year and the frequency of adverse events. Other outcome measures included progression-free survival and systemic therapy-free survival. Exploratory analyses included PD-L1 protein expression.

RESULTS:Forty two percent (5/12) of patients had a PSAs of<0.6 ng/mL at one year though only 2 of these patients had recovered their testosterone at this time point. Median progression-free survival was 14 months, and median systemic therapy-free survival was 17.5 months. PD-L1 expression was not detectable by IHC in patients with evaluable tissue. All adverse events were grade ≤2, and there were no apparent complications from cryotherapy.

CONCLUSIONS:Whole-prostate cryoablation combined with short-term androgen deprivation and pembrolizumab treatment was well tolerated and no safety concerns were observed in men with oligometastatic prostate cancer. Though local disease appeared effectively treated in the majority of men, the regimen only infrequency led to sustained disease control following testosterone recovery.

BACKGROUND:Cryotherapy is a commonly discussed method for treatment of basal cell carcinoma skin cancer. Some uncertainty remains about its efficacy relative to other modalities.

OBJECTIVE:To determine the efficacy and adverse events profile of cryotherapy for the treatment of basal cell carcinoma compared to other therapeutic options or non-intervention.

METHODS:We systematically searched PubMed, OVID, Cochrane Library, EMBASE, CINHAL, and CANCERLIT databases for the following terms:"cryotherapy", AND"basal cell carcinoma", OR"cryosurgery"OR"cryoablation"up to April 2018. Two independent reviewers screened the results and extracted the data. Study endpoints included basal cell carcinoma recurrence, cosmetic outcome, and healing time. Study quality was assessed using the Jadad scale.

RESULTS:Six clinical studies met our inclusion criteria. The efficacy and safety of cryotherapy alone or with curettage in the treatment of primary superficial and nodular basal cell carcinoma was comparable to photodynamic therapy and surgery, respectively. Cryotherapy was inferior to radiation in terms of recurrence rate. Most patients had better cosmetic outcomes with photodynamic therapy and surgery compared to cryotherapy alone, and cryotherapy with curettage.

CONCLUSION:Current available data suggests equivalent efficacy of cryotherapy alone compared to photodynamic therapy or surgery, but inferior to radiotherapy. More studies are necessary to draw definitive conclusions.

INTRODUCTION:The neuroprotective effects of hypothermia in acute ischemic stroke are well documented. However, the mechanisms involved in the effects remain to be clearly elucidated and the role of hypothermia on long-term white matter integrity after acute ischemic stroke has yet to be investigated.

AIMS:To investigate the role of mild focal hypothermia on long-term white matter (WM) integrity after transient cerebral ischemia.

RESULTS:Mild focal hypothermia treatment immediately after ischemic stroke significantly promotes WM integrity 28 days after the occlusion of the middle cerebral artery (MCAO) in mice. Higher integrity of white matter, lower activation of total microglia, less infarct volume, and better neurobehavioral function were detected in hypothermia-treated mice compared to normothermia-treated mice. Furthermore, we found that hypothermia could decrease detrimental M1 phenotype microglia and promote healthy M2 phenotype microglia. In vitro, results also indicated that hypothermia promoted oligodendrocytes differentiation and maturation after oxygen glucose deprivation.

CONCLUSION:Hypothermia promotes long-term WM integrity and inhibits neuroinflammation in a mouse model of ischemic brain injury.

PURPOSE:The aim of this study is to compare cryotherapy made only with water and cryotherapy made with chamomile infusion for prevention and reduction of intensity of oral mucositis in patients with cancer receiving 5-fluorouracil and leucovorin.

METHOD:This is a randomized pilot study with two groups: cryotherapy made only with water (control group, n = 18) and cryotherapy made with chamomile infusion (chamomile group, n = 20). Both groups were instructed to swish the ice around in their oral cavity for at least 30 min during chemotherapy. Assessment of oral mucosa occurred on days 8, 15, and 22 after the first day of chemotherapy.

RESULTS:Fifty percent of the patients in the control and 30 % in the chamomile group developed oral mucositis. Mouth pain score was higher in patients in the control group on all evaluations (p = 0.02 for day 8, p = 0.09 for day 15, and p = 0.14 for day 22). Patients in the chamomile group never developed mucositis with grade 2 or higher. Presence of ulceration was statistically significant on day 8 (16 % in the control vs. 0 % in the chamomile group, p = 0.10), but not in days 15 and 22, although 11 % still had ulcerations in the control group and none in the chamomile group.

CONCLUSION:The occurrence of oral mucositis was lower in patients in the chamomile group than in the control group. When compared to the controls, the chamomile group presented less mouth pain and had no ulcerations. Cryotherapy was well tolerated by both groups, and no toxicity related to chamomile was identified.

The red cell glutathione levels of 10 healthy volunteers who are accustomed to winter-swimming were measured before and after this short-term whole body exposition to hypothermic environment. From the increases of the erythrocytic level of oxidized glutathione (GSSG) and of GSSG: total glutathione ratio an extensive formation of oxygen free radicals during and following the exposition to the intensive cold stimulus was concluded. That is in accordance with the finding on the drastic decrease of the concentration of uric acid as an important radical scavenger of the human blood plasma. Furthermore, the initial erythrocytic concentrations of reduced glutathione (GSH) and GSSG of subjects accustomed to winter-swimming were compared with those of healthy control persons who are not accustomed to regular winter-swimming. The markedly increased concentration of GSH and the reduced GSSG:total glutathione ratio in the erythrocytes of winter-swimmers reflect the adaptation to a regular oxidative stress. This antioxidative adaptation is postulated as a new basic mechanism of the hardening by exposition to an intensive short-term cold stimulus often applied within the hydrotherapy.

Apple stem grooving virus (ASGV), a difficult-to-eradicate virus from apple propagative materials, causes serious damage to apple production. The use of virus-free plants has been and is an effective strategy for control of plant viral diseases. This study aimed to eradicate ASGV from virus-infected in-vitro-cultured shoots of four apple cultivars and one rootstock by combining thermotherapy with cryotherapy. In vitro stock shoots infected with ASGV were thermo-treated using an alternating temperature of 36°C (day) and 32°C (night). Shoot tips were excised from the treated stock shoots and subjected to cryotherapy. Results showed that, although thermotherapy did not influence shoot survival rates, it reduced shoot growth and proliferation of in vitro shoots. Shoot regrowth rates decreased while virus eradication frequencies increased in cryo-treated shoot tips as time durations of thermotherapy increased from 0 to 6 weeks. Shoot regrowth and frequency of virus eradication were positively and negatively correlated, respectively, with the size of shoot tips. The protocol established here yieldedshoot regrowth rates and virus eradication frequencies of 33 to 76% and 30 to 100%, respectively, in the four apple cultivars and one rootstock. Thermotherapy altered virus distribution patterns, subsequently resulting in production of a larger virus-free area in the thermo-treated shoot tips. Manycells in the top layers of apical dome and some cells in the youngest leaf primordia survived in cryo-treated shoot tips; these cells were most likely free of virus infection. Thus, plants regenerated from the procedure of combining thermotherapy with cryotherapy were free of ASGV, as judged by reverse-transcription polymerase chain reaction. To the best of our knowledge, this is the widest-spectrum technique reported thus far for the production of ASGV-free plants and provides a novel biotechnology for the production of virus-free plants in Malus spp.

BACKGROUND:Our previous study showed that cotton-swab cryotherapy is an alternative treatment modality for oral leukoplakia.

METHODS:This study used liquid nitrogen spray with a cryogun (cryogun cryotherapy) to treat 60 oral leukoplakia lesions.

RESULTS:Complete regression was achieved in all 60 oral leukoplakia lesions after cryogun cryotherapy. We found that 60 oral leukoplakia lesions treated with cryogen cryotherapy needed significantly fewer mean treatments (3.1± 1.3) to achieve complete regression than 60 previously reported oral leukoplakia lesions treated with cotton-swab cryotherapy (mean, 6.3 ± 3.8 treatments). Oral leukoplakia lesions on oral mucosal sites other than the tongue,<2 cm(2) , with epithelial dysplasia, or with a surface keratin thickness<55μm required significantly fewer cryogun cryotherapy treatments to achieve complete regression.

CONCLUSIONS:For treatment of oral leukoplakia, the cryogun cryotherapy needed fewer mean treatments to achieve complete regression of the lesions than the cotton-swab cryotherapy.

Novel approaches with checkpoint inhibitors in immunotherapy continue to be essential in the treatment of non-small cell lung cancer (NSCLC). However, the low rate of primary response and the development of acquired resistance during the immunotherapy limit their long-term effectiveness. The underlying cause of acquired resistance is poorly understood; potential management strategies for patients with acquired resistance are even less clear. Here, we report the case of a 75-year-old female smoker with cough, fatigue, and weight loss that was found to have an 8.6 cm right upper lobe lung lesion with local invasion, adenopathy, and a malignant pericardial effusion. This lesion was biopsied and identified to be cT3N3M1b squamous cell cancer of the lung without any recognizable PD-L1 expression on tumor cells. For her metastatic NSCLC, the patient underwenttwo lines of conventional chemotherapy before initiation of combination immunotherapy with an anti-PD-L1 and anti-CTLA-4 antibody. Though she initially achieved a response, she thereafter progressed and developed immunotherapy resistant lymph nodal metastasis. While cervical lymph nodes could be surgically removed, another metastasis in an aortocaval area required a more sensitive therapy like thermal ablation. The aortocaval node was partially treated with a single treatment of cryotherapy and demonstrated durable complete response. Cryotherapy for checkpoint immunotherapy resistant metastasis appears to be a safe and feasible treatment for treating metastatic disease in non-small cell lung cancer. The prospect of cryotherapy adjuvancy may enable local control of metastatic disease after initial response to immune checkpoint immunotherapy and may impact on overall outcomes.

PURPOSE:This randomized phase II study was conducted to investigate the efficacy of cryotherapy in preventing peripheral neuropathy and dermatological adverse events in breast cancer patients treated with weekly paclitaxel.

METHODS:Patients treated with 12 weekly doses of paclitaxel for breast cancer were randomized (1:1) into a cryotherapy or control group. The primary endpoint was the percentage of patients with a marked decrease in the Functional Assessment of Cancer Therapy-Neurotoxicity (FACT-NTX) score. The secondary endpoints were Patient Neurotoxicity Questionnaire (PNQ), Common Terminology Criteria for Adverse Event (CTCAE) for peripheral neuropathy, and FACT-Taxane score.

RESULTS:Forty-four patients were randomly assigned to the cryotherapy (n = 22) or control groups (n = 22). The percentage of patients with a marked decrease in FACT-NTX scores was significantly lower in the cryotherapy group than in the control group (41 vs. 73%, p = 0.03). The incidence of CTCAE grade ≥ 2 sensory (p = 0.001) and motor peripheral neuropathy (p = 0.01), and PNQ grade D or higher for sensory peripheral neuropathy (p = 0.02), and decrease in the FACT-Taxane score (p = 0.02) were also significantly lower in the cryotherapy group than in the control group. There were no serious side effects associated with cryotherapy.

CONCLUSION:Cryotherapy is an effective approach for prevention of peripheral neuropathy and dermatological adverse events in breast cancer patients treated with weekly paclitaxel.

BACKGROUND:Chronic rhinitis impacts 60 million Americans and is associated with significant costs for patients. Although medical treatments are first line, some patients require surgical intervention such as vidian or posterial nasal neurectomy. Previous reviews have investigated the role of surgical management in chronic rhinitis, but none have investigated a longstanding treatment with recent interest: cryotherapy.

OBJECTIVE:To identify the safety, efficacy, and durability of treatment response of cryotherapy in treating chronic rhinitis.

METHODS:A systematic literature review was performed to identify studies that investigated the utility of cryotherapy in chronic rhinitis. Only studies with the primary objective of assessing the efficacy of cryotherapy on chronic rhinitis were included. Patients were classified as allergic rhinitis, nonallergic rhinitis (vasomotor rhinitis), or mixed rhinitis using the original author's criteria. Data were extracted regarding reported complications, treatment efficacy, and length of follow-up.

RESULTS:A total of 110 abstracts were identified, of which 15 were included in this review. Epistaxis and nasal obstruction were commonly reported complications. No serious adverse events were reported. For obstructive symptoms,"reduced"symptoms were reported in 63.4% to 100% of patients. In regard to rhinorrhea, reports of reduced symptoms were experienced from 77% to 100% of patients. Seven studies used only patient-reported improvements without stratifying results based on symptom type; general improvements ranged from 67% to 100%. Nine studies noted symptom improvement in nonallergic cohorts ranging from 67% to 97.5% of patients. Four studies noted improvement in allergic cohorts ranging from 63.4% to 80% of patients. Two studies noted improvement in patients with mixed pictures ranging from 92.5% to 100%.

CONCLUSIONS:Although cryotherapy appears safe and efficacious, heterogeneous past investigations with low-quality evidence make strong, evidence-based recommendations difficult to make. Further study with validated metrics and controlled populations is certainly warranted and should be encouraged.

The aim of this article was to review current evidence about cryotherapy in inflammatory rheumatic diseases (therapeutic and biological effects). For therapeutic effects, we performed a systematic review (PubMed, EMBASE, Cochrane Library, LILACS databases, unpublished data) and selected studies including non-operated and non-infected arthritic patients treated with local cryotherapy or whole-body cryotherapy. By pooling 6 studies including 257 rheumatoid arthritis (RA) patients, we showed a significant decrease in pain visual analogic scale (mm) and 28-joint disease activity score after chronic cryotherapy in RA patients. For molecular pathways, local cryotherapy induces an intrajoint temperature decrease, which might downregulate several mediators involved in joint inflammation and destruction (cytokines, cartilage-degrading enzymes, proangiogenic factors), but studies in RA are rare. Cryotherapy should be included in RA therapeutic strategies as an adjunct therapy, with potential corticosteroid and nonsteroidal anti-inflammatory drug dose-sparing effects. However, techniques and protocols should be more precisely defined in randomized controlled trials with stronger methodology.

Endoscopic cryotherapy is a relatively new thermal ablative modality used for the treatment of neoplastic lesions of the esophagus. It relies on cycles of rapid cooling and thawing to induce tissue destruction with a cryogen (liquid nitrogen or carbon dioxide) leading to intra and extra-cellular damage. Surgical treatment was once considered the standard therapeutic intervention for neoplastic diseases of the esophagus and is associated with considerable rates of morbidity and mortality. Several trials that evaluated cryotherapy in Barrett's esophagus (BE) associated neoplasia showed reasonable efficacy rates and safety profile. Cryotherapy has also found applications in the treatment of esophageal cancer, both for curative and palliative intent. Cryotherapy has also shown promising results as salvage therapy in cases refractory to radiofrequency ablation treatment. Cryoballoon focal ablation using liquid nitrogen is a novel mode of cryogen delivery which has been used for the treatment of BE with dysplasia and squamous cell carcinoma. Most common side effects of cryotherapy reported in the literature include mild chest discomfort, esophageal strictures and bleeding. In conclusion, cryotherapy is an effective and safe method for the treatment of esophageal neoplastic processes, ranging from early stages of low grade dysplasia to esophageal cancer.

Introduction:Genital warts are a frequent form of sexually transmitted disease. Cryotherapy represents the first line of therapy. Healing occurs in 94%, and recurrence in 10% . Side effects are common during the treatment.

Aim:The aim of this study is to determine the successfulness of cryotherapy of genital warts, frequency of recurrence, and side effects.

Patients and methods:In a retrospective study, data from 50 women with genital warts who were treated in the Gynecological Centre"Dr Mahira Jahić"in Tuzla in a period from 2012-2018 were analyzed. Every woman was treated with cryotherapy. Treatments were repeated every 7 days, maximal number of treatments being 7. In processing of data, X2statistical method was used.

Results:50% (N-25) of genital warts eliminated after 3 treatments with cryotherapy . Genital warts are eliminated in 78% (N-39) of women, while this treatment was unsuccessful in 18% (N-9). Recurrence after 3 months in 4% (N-2). Most common side effect was exudation in 78% (N-39), swelling in 72% (N-36) and pain in 66% (N-33). PAP smears in women with genital warts in 64% (N-34) of cases were inflammatory benign changes, while in 36% (N-18) mild abnormal changes in cells ASCUS and LSIL were found. LSIL lesions of cervix are more common (p<0,01) in women with genital warts of vulva.

Conclusion:Cryotherapy is a method with a high success rate in healing of genital warts, and it decreases the concentration of HPV virus and removes the trigger that allows the development of cancer.

Our objective was to examine cryotherapy experiences among women who received treatment for cervical intraepithelial neoplasia in a cervical cancer prevention project in rural Peru. The sample consisted of all women receiving cryotherapy during a 4-month period (July through October 2001). Structured interviews were conducted to collect information about the adequacy of information provision, women's satisfaction with cryotherapy, their ability to comply with postcryotherapy recommendations and condom use, their experience with cryotherapy side effects, and their satisfaction with cryotherapy follow-up. Of the 224 women who were interviewed, user satisfaction with cryotherapy treatment was generally good. A few women engaged in sex earlier than 30 days after treatment, primarily due to partner pressure to resume sex and the women's inability to successfully negotiate abstention from sex. These couples were not always able to use condoms. The percentage of women reporting vaginal discharge was within the range of responses reported in other studies. Cryotherapy appears to be acceptable to women in low-resource settings such as Peru.

INTRODUCTION:Common warts are hyperkeratotic, benign cutaneous growths caused by types 1, 2, and 7 Human papilloma viruses. Different modalities are available to treat warts. Cryotherapy is one of the most common and effective treatments for common warts. Trichloroacetic acid (TCA), in high concentrations, can be used as a therapeutic modality.

OBJECTIVES:The aim of this study is to compare the efficacy and safety of cryotherapy using liquid nitrogen (spray method) versus trichloroacetic acid 90% in treatment of common warts.

PATIENTS AND METHODS:Thirty-five patients with 414 common warts, from the Dermatology outpatient clinic, Assiut University Hospital, were enrolled in this study. We used two techniques for the treatment of common warts. The lesions in each patient were divided into two groups (A and B), group A treated by cryotherapy while group B treated by trichloroacetic acid (TCA) 90%.

RESULTS:There was significant decrease in the size of the warts in both groups. There were statistically significant better results among group A than group B regarding the mean percentage of improvement (90.11 ± 27.92 vs 26.19 ± 42.93, respectively; P < 0.001) and grade of improvement, where good response was obtained in 89.2% in group A compared with 26.2% in group B (P < 0.001). Complete cure was significantly higher in group A (83.1%) than group B (21.3%; P < 0.001). However, side effects were significantly higher among group A than group B.

CONCLUSION:Cryotherapy is more effective than TCA 90% in treatment of common wart. TCA 90% has lesser complications than cryotherapy.

When exercises are done in intense or exhaustive modes, several acute biochemical mechanisms are triggered. The use of cryotherapy as cold-water immersion is largely used to accelerate the process of muscular recovery based on its anti-inflammatory and analgesic properties. The present study aimed to study the biochemical effects of cold-water immersion treatment in mice submitted to exercise-induced exhaustion. Swiss albino mice were divided into 4 treatment groups: control, cold-water immersion (CWI), swimming exhaustive protocol (SEP), and SEP+CWI. Treatment groups were subdivided into times of analysis: 0, 1, 3, and 5 days. Exhaustion groups were submitted to one SEP session, and the CWI groups submitted to one immersion session (12 min at 12°C) every 24 h. Reactive species production, inflammatory, cell viability, and antioxidant status were assessed. The SEP+CWI group showed a decrease in inflammatory damage biomarkers, and reactive species production, and presented increased cell viability compared to the SEP group. Furthermore, CWIincreased acetylcholinesterase activity in the first two sessions. The present study showed that CWI was an effective treatment after exercise-induced muscle damage. It enhanced anti-inflammatory response, decreased reactive species production, increased cell viability, and promoted redox balance,which could decrease the time for the recovery process.

Objective:The aim of the study was to estimate the impact of whole-body cryotherapy (WBC) and subsequent kinesiotherapy on oxidative stress and lipid profile when performed in a closed cryochamber on healthy subjects.

Material and Methods:The effect of ten WBC procedures lasting 3 minutes a day followed by a 60-minute session kinesiotherapy on oxidative stress and lipid profile in healthy subjects (WBC group,= 16) was investigated. The WBC group was compared to the kinesiotherapy only (KT;= 16) group. The routine parameters of oxidative stress (antioxidant enzymatic and nonenzymatic antioxidant status, lipid peroxidation products, total oxidative status (TOS), and oxidative stress index (OSI)) and lipid profile were estimated one day before the beginning and one day after the completion of the research program.

Results:After treatment, in the WBC group, a significant decrease of oxidative stress markers (TOS and OSI) and a significant increase of total antioxidant capacity were observed. The activity of plasma SOD-Mn and erythrocyte total SOD increased significantly in the WBC group. In the KT group, the erythrocyte activity of total SOD, CAT, and GR decreased significantly after the treatment. The levels of T-Chol and LDL-Chol decreased significantly after treatment in both groups, but the observed decrease of these lipid parameters in the WBC group was higher in comparison to the KT group. The level of TG decreased significantly after treatment in the WBC group only.

Conclusion:WBC performed in a closed cryochamber followed by kinesiotherapy improves lipid profile and decreases oxidative stress in healthy subjects.