Focal therapy versus radical prostatectomy and external beam radiotherapy as primary treatment options for non-metastatic prostate cancer: results of a cost-effectiveness analysis.

AIMS: Focal therapy treats individual areas of tumour in non-metastatic prostate cancer in patients unsuitable for active surveillance. The aim of this work was to evaluate the cost-effectiveness of focal therapy versus prostatectomy and external beam radiotherapy (EBRT). MATERIALS AND METHODS: A Markov cohort health state transition model with four health states (stable disease, local recurrence, metastatic disease and death) was created, evaluating costs and utilities over a 10-year time horizon for patients diagnosed with non-metastatic prostate cancer. National Health Service (NHS) for England perspective was used, based on direct healthcare costs. Clinical transition probabilities were derived from prostate cancer registries in patients undergoing radical prostatectomy, EBRT and focal therapy using cryotherapy (Boston Scientific) or high-intensity focused ultrasound (HIFU) (Sonablate). Propensity score matching was used to ensure that at-risk populations were comparable. Variables included age, prostate-specific antigen (PSA), International Society of Urological Pathology (ISUP) grade group, maximum cancer core length (mm), T-stage and year of treatment. RESULTS: Focal therapy was associated with a lower overall cost and higher quality-adjusted life year (QALY) gains than either prostatectomy or EBRT, dominating both treatment strategies. Positive incremental net monetary benefit (NMB) values confirm focal therapy as cost-effective versus the alternatives at a willingness to pay (WTP) threshold of £30,000/QALY. One-way deterministic sensitivity analyses revealed consistent results. LIMITATIONS: Data used to calculate the transition probabilities were derived from a limited number of hospitals meaning that other potential treatment options were excluded. Limited data were available on later outcomes and none on quality of life data, therefore, literature-based estimates were used. CONCLUSIONS: Cost-effectiveness modelling demonstrates use of focal therapy (cryotherapy or HIFU) is associated with greater QALY gains at a lower overall cost than either radical prostatectomy or EBRT, representing good value for money in the NHS.

Focal therapy can be used for the primary treatment of individual areas of cancer in those patients with prostate cancer whose disease has not spread (localized or non-metastatic prostate cancer) and whose disease is unsuitable for active monitoring. Focal therapy in these patients results in similar control of the cancer to more invasive therapies, such as surgical removal of the prostate and radiotherapy, with the benefit of fewer sexual, urinary and rectal side effects. This work considered whether using focal therapy (either freezing the cancer cells using cryotherapy or using high-intensity focused ultrasound [HIFU] to destroy cancer cells) was good value for money in the National Health Service (NHS) compared with surgery or radiotherapy. An economic model was developed which considered the relative impact of treatment with focal therapies, surgery or radiotherapy within the NHS in England. Previously collected information from people undergoing treatment for their prostate cancer, together with published literature and clinical opinion, was used within the model to predict the treatment pathway, costs incurred and the results of treatment in terms of patient benefits (effectiveness and quality of life). The model showed that focal therapy using either cryotherapy or HIFU was associated with a lower overall cost and higher patient benefit than either surgery or radiotherapy, indicating that focal therapy represents good value for money in the NHS.

Nephron Sparing Treatment (NEST) for Small Renal Masses: A Feasibility Cohort-embedded Randomised Controlled Trial Comparing Percutaneous Cryoablation and Robot-assisted Partial Nephrectomy.

There is a paucity of high-level evidence on small renal mass (SRM) management, as previous classical randomised controlled trials (RCTs) failed to meet accrual targets. Our objective was to assess the feasibility of recruitment to a cohort-embedded RCT comparing cryoablation (CRA) to robotic partial nephrectomy (RPN). A total of 200 participants were recruited to the cohort, of whom 50 were enrolled in the RCT. In the RCA intervention arm, 84% consented (95% confidence interval [CI] 64-95%) and 76% (95% CI 55-91%) received CRA; 100% (95% CI 86-100%) of the control arm underwent RPN. The retention rate was 90% (95% CI 79-96%) at 6 mo. In the RPN group 2/25 (8%) were converted intra-operative to radical nephrectomy. Postoperative complications (Clavien-Dindo grade 1-2) occurred in 12% of the CRA group and 29% of the RPN group. The median length of hospital stay was shorter for CRA (1 vs 2 d; p = 0.019). At 6 mo, the mean change in renal function was -5.0 ml/min/1.73 m2 after CRA and -5.8 ml/min/1.73 m2 after RPN. This study demonstrates the feasibility of a cohort-embedded RCT comparing CRA and RPN. These data can be used to inform multicentre trials on SRM management. PATIENT SUMMARY: We assessed whether patients with a small kidney tumour would consent to a trial comparing two different treatments: cryoablation (passing small needles through the skin to freeze the kidney tumour) and surgery to remove part of the kidney. We found that most patients agreed and a full trial would therefore be feasible.

The Safety and Efficacy of Cryotherapy in the Prevention of Paclitaxel-Induced Neuropathy: A Systematic Review.

The chemotherapeutic agent paclitaxel has significantly enhanced the treatment of various types of cancer. However, the quality of life of cancer patients is often impacted by the painful and dose-restrictive paclitaxel side effect known as paclitaxel-induced peripheral neuropathy (PIPN). A non-pharmacological method called cryotherapy has shown promise in alleviating PIPN-related symptoms. In this systematic review, we aimed to evaluate the safety and effectiveness of cryotherapy in preventing PIPN. The review analyzed four randomized controlled trials (RCTs) involving individuals treated with paclitaxel for breast and gynecological cancer. Cryotherapy showed success in lowering PIPN symptoms in several studies, as judged by various outcome measures, although the findings varied. The safety profile of cryotherapy was typically good, with minimal side effects. However, methodological variations and small sample sizes in the studies analyzed limit drawing definitive conclusions from them. To obtain conclusive evidence, studies with standardized techniques and larger sample sizes are required. Further research is necessary to understand cryotherapy's potential mechanisms and long-term effects. This review highlights the potential of cryotherapy in the management of PIPN, explains how it works, and suggests future research topics to improve its application.

An extraoral approach to intraoral cooling-a feasibility study in non-cancer patients.

BACKGROUND: Cryotherapy, using ice chips (IC) is an effective strategy to prevent chemotherapy-induced oral mucositis (OM) in selected cancer patient cohorts. However, although effective, use of IC may cause adverse reactions, e.g., nausea, numbness, and shooting pain in the teeth, which could have an adverse impact on the medical treatment. Furthermore, IC requires water of good quality to minimize risk of serious systemic infections. To eliminate these disadvantages, novel cooling devices have emerged as alternative cooling modalities. Thus, the aim was to evaluate the efficacy and tolerability profile of extraoral cooling for intraoral temperature reduction. SUBJECTS AND METHODS: This experimental pilot study was conducted at the Institute of Odontology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. In total, six healthy volunteers were enrolled in this study. At baseline and following 30-, and 60 min of cooling with the extraoral cooling device, intraoral mucosal temperatures were measured using a thermographic camera, and a questionnaire related to tolerability was completed. RESULTS: Following 30-, and 60 min of cooling, the intraoral temperature decreased with 2.0 °C and 2.3 °C, respectively. Extraoral cooling was well tolerated, and all subjects endured the entire cooling session of 60 min. CONCLUSION: Extraoral cooling reduces intraoral mucosal temperatures and is a well-tolerated cooling modality.

Effects of 3-week repeated cold water immersion on leukocyte counts and cardiovascular factors: an exploratory study.

Aim: This exploratory study aimed to investigate the effects of a 3-week repeated cold water immersion (CWI) intervention on leukocyte counts and cardiovascular factors (mean arterial pressure [MAP], heart rate [HR]) in healthy men. Methods: A total of n = 12, non-cold-adapted men (age: 25.2 ± 4.0 years; height: 177.8 ± 5.6 cm; weight: 73.8 ± 6.5 kg) were randomly allocated to the CWI or control (CON) group. The CWI group underwent a 3-week repeated CWI intervention (12min at 7°C, 4x/week). The CON group did not receive any cold exposure or therapy. Total leukocyte numbers and proportions (neutrophils, basophils, eosinophils, monocytes, lymphocytes) and cardiovascular factors (MAP, HR) were assessed at baseline and after the 3-week intervention period. Results: Total leukocyte count decreased in CWI (p = 0.027, 95% CI -2.35 to -0.20 × 103/µL) and CON (p = 0.043, 95% CI -2.75 to -0.50 × 103/µL). CWI showed a decrease in neutrophil number (p = 0.028, 95% CI -1.55 to -0.25 × 103/µL) and proportion (p = 0.046, 95% CI -6.42 to 0.56%). In contrast, CON showed no significant change (p > 0.05). No differences were found for other leukocyte subtypes in CWI or CON (all p > 0.05). MAP (p = 0.028, 95% CI -17 to -8 mmHg) and HR (p = 0.027, 95% CI -7 to -2 bpm) were reduced in CWI, whereas CON showed no change (p > 0.05). Conclusion: The results suggest no relevant effects of 3-week repeated CWI on leukocyte counts in healthy men. Due to methodological limitations, the effects on the investigated cardiovascular factors remain unclear. Further studies with larger sample sizes are needed to examine the effects on immune function and cardiovascular health.

Cryoablation and immunity in non-small cell lung cancer: a new era of cryo-immunotherapy.

Despite remarkable advances in tumor response and patient survival in the past decade, systemic immunotherapies for lung cancer result in an objective response in only around half of patients treated. On the basis of this limitation, combination strategies are being investigated to improve response rates. Cryoablation has been proposed as one such technique to induce immunogenic cell death and synergize with systemic immunotherapies, including immune checkpoint inhibitors. Cryoablation has been traditionally delivered percutaneously with imaging guidance although recent technological advances allow for bronchoscopic delivery. Herein, we review the pre-clinical and clinical evidence for the use of cryoablation in non-small cell lung cancer and potential induction of anti-tumor immunity. We highlight ongoing studies involving this approach and propose areas of future investigation.

Active recovery vs hot- or cold-water immersion for repeated sprint ability after a strenuous exercise training session in elite skaters.

This study compared the acute effects of three recovery methods: active recovery (AR), hot- and cold-water immersion (HWI and CWI, respectively), used between two training sessions in elite athletes. Twelve national-team skaters (7 males, 5 females) completed three trials according to a randomized cross-over study. Fifteen minutes after an exhaustive ice-skating training session, participants underwent 20 min of HWI (41.1 ± 0.5°C), 15 min of CWI (12.1 ± 0.7°C) or 15 min of active recovery (AR). After 1 h 30 min of the first exercise, they performed a repeated-sprint cycling session. Average power output was slightly but significantly higher for AR (767 ± 179 W) and HWI (766 ± 170 W) compared to CWI (738 ± 156 W) (p = 0.026, d = 0.18). No statistical difference was observed between the conditions for both lactatemia and rating of perceived exertion. Furthermore, no significant effect of recovery was observed on the fatigue index calculated from the repeated sprint cycling exercises (p > 0.05). Finally, a positive correlation was found between the average muscle temperature measured during the recoveries and the maximal power output obtained during cycling exercises. In conclusion, the use of CWI in between high-intensity training sessions could slightly impair the performance outcomes compared to AR and HWI. However, studies with larger samples are needed to confirm these results, especially in less trained athletes.

Effect of Cryotherapy on Fracture Resistance of Neoniti Rotary Instruments.

Objectives: Nickel-titanium (NiTi) rotary files were introduced to optimize root canal instrumentation in endodontic treatment. However, despite the numerous advantages of NiTi instruments, they may unexpectedly break during clinical use, resulting in obstruction of the root canal system. This investigation aimed to assess the effect of cryotherapy on fracture resistance of Neoniti rotary files. Materials and Methods: This in vitro, study was conducted on 20 Neoniti rotary files with #35 tip size and 6% taper in two groups with and without cryogenic treatment (N=10). For cryogenic treatment, the files were immersed in liquid nitrogen at -196°C for 24 hours. Next, the Neoniti files in both groups were subjected to cyclic fatigue testing in a hand-piece operating at 500 rpm with 20 N/cm torque. The files were rotated until fracture and the fracture time as well as the number of cycles to fracture were recorded for each file. The two groups were compared by independent t-test at 0.05 level of significance. Results: The number of cycles to fracture was 235700±50649.22 in the control and 280600±22979.21 in the cryotherapy group. The mean fracture time was 471.40±101.29 and 561.20±45.958 seconds in the control and cryotherapy groups, respectively. Significant differences in both variables were noted between the two groups (P<0.05). Conclusion: Based on our findings, utilizing cryogenic treatment may enhance the fracture resistance of rotary instruments, making it a beneficial practice for dental clinicians to adopt. By using cryogenically treated rotary instruments, clinicians can potentially reduce the risk of file fracture during dental procedures.

Effect of cryotherapy duration on experimentally induced connective tissue inflammation in vivo.

Objectives: This study tested the hypothesis that cryotherapy duration influences lipopolysaccharide (LPS)-induced inflammation in a rat model. Materials and Methods: Six Wistar rats (Rattus norvegicus albinus) were used. Five sites were selected per animal and divided into 5 groups: a negative control group (NC), 2 positive control groups (PC1 and PC2), and 2 experimental groups (E1 and E2). Cryotherapy was applied for 1 minute (E1) or 5 minutes (E2). An acute inflammatory response was induced in the PC and E groups via subcutaneous administration of 0.5 mL/kg. In the PC2 group, a catheter was inserted without additional treatment. For the E1 and E2 groups, 2.5°C saline solution was administered through the implanted catheters for 1 and 5 minutes, respectively. The rats were sacrificed, and samples were obtained and processed for histological analysis, specifically examining the presence of polymorphonuclear neutrophils and hemorrhage. The χ2 test was used to compare the presence of acute inflammation across groups. Dependent variables were compared using the linear-by-linear association test. Results: Inflammation and hemorrhage varied significantly among the groups (p = 0.001). A significantly higher degree of acute inflammation was detected (p = 0.0002) in the PC and E1 samples than in the E2 group, in which cryotherapy was administered for 5 minutes. The PC and E1 groups also exhibited significantly greater numbers of neutrophils (p = 0.007), which were essentially absent in both the NC and E2 groups. Conclusions: Cryotherapy administration for 5 minutes reduced the acute inflammation associated with LPS and catheter implantation.

Outcomes of Holmium Laser, Cryoablation, and Budesonide Inhalation for Treating Severe Central Airway Stenosis in Infants.

BACKGROUND: Central airway stenosis (CAS) in infants is characterized by dysphonia, dyspnea, cyanosis, repeated apnea, and infection. This case series study aimed to evaluate the safety and efficacy of holmium laser, cryoablation and budesonide inhalation in treating infants with severe CAS. METHODS: This retrospective study reviewed medical records data of 28 infants with severe CAS who underwent holmium laser treatment with cryoablation and/or balloon dilatation and budesonide inhalation therapy at Shanghai Children's Medical Center between June 2014 and May 2020. Outcomes were defined as treatment success when the stenotic area was <25% for the normal age group with stable reopening diameter at one-year follow-up. RESULTS: Patients' mean age was 12.8 ± 8.8 months and 17 (60%) were male. Sixteen cases had web-like stenosis and 12 had scar contracture stenosis. Among 16 patients with web-like stenosis, 8 (50%) underwent balloon dilation with cryotherapy and 8 (50%) underwent balloon dilation only; treatment success was achieved in 10 (62.5%) cases and after revised treatments in 5 (31.25%) cases. Among 12 patients with scar contracture stenosis, 6 (50%) underwent balloon dilation with cryotherapy, 4 (33.3%) underwent cryotherapy and 2 (16.7%) underwent balloon dilation only; treatment success was achieved in 3 (23.1%) cases and after 1-4 revised treatments in 8 (61.5%) cases. Symptoms of the 2 unsuccessful (7.1%) cases were relieved after tracheal stent insertion. Neither severe adverse events nor complications were observed during follow-up. CONCLUSION: Holmium laser with cryoablation followed by budesonide inhalation therapy safely and effectively cleans stenotic tissues and maintains airway reopening. Balloon dilation after holmium laser is recommended for treating web-like stenosis.

Effects of spray cryotherapy on cough receptors and airway microenvironment in a canine model of chronic bronchitis.

The aim of this study was to explore the effects of spray cryotherapy (SCT) on cough receptors and airway microenvironment in a canine model of chronic bronchitis. We examined the expression of transient receptor potential vanilloid 1/4 (TRPV1/4) and the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) at the gene and protein levels before and after SCT. In addition, we explored whether TRPV1/4 could regulate inflammatory factors via mediator adenosine triphosphate (ATP). The levels of ATP and cytokines in alveolar lavage fluid and cell supernatant were measured using ELISA. SCT effectively downregulated the expression of TRPV1/4 and SP/CGRP in canine airway tissues with chronic bronchitis and reduced the levels of inflammatory mediators and cytokines that affect cough receptor sensitivity, achieving cough relief. TRPV1/4 - ATP - inflammatory cytokines axis has been demonstrated at the cellular level, which in turn modulate the milieu of the airways and promote the formation of a cough feedback loop. Our study has fully revealed the specific mechanism of SCT in treating cough in a canine model of chronic bronchitis, providing a solid theoretical basis for future clinical treatment.

Clinical Outcomes of Bronchoscopic Cryotherapy for Central Airway Obstruction in Adults: An 11-Years' Experience of a Single Center.

BACKGROUND: Although bronchoscopic cryotherapy (BC) is a pragmatic modality for recanalization of central airway obstruction (CAO), the risk of complications, such as bleeding, remains a concern. This study aimed to present the clinical outcomes of BC and evaluate the factors associated with its complications. METHODS: In this retrospective study, we reviewed the medical records of patients who underwent BC for CAO at the Asan Medical Center, South Korea. Most sessions were conducted via flexible bronchoscopy under moderate sedation. A multivariate logistic regression analysis was used to identify the factors associated with the success rate and complications. RESULTS: BC was performed in 262 sessions in 208 patients between January 2009 and December 2020. The most common cause of cryotherapy was recanalization of the endobronchial tumor related CAO (233/262, 88.9%). More than partial re-establishment of airway patency was achieved in 211 of 233 (90.6%) sessions. The success rate did not differ significantly in the multivariate logistic regression analysis. The most common complication was intrabronchial bleeding (78/233, 35.5%); however, severe bleeding occurred only in one case (0.4%). Univariate and multivariate logistic regression analyses revealed that diabetes mellitus (odds ratio [OR] = 2.820, P = 0.011), respiratory failure before BC (OR = 3.546, P = 0.028), and presence of distal airway atelectasis (OR = 0.417, P = 0.021) were independently associated with moderate to severe intrabronchial bleeding, while the histologic type of tumor was not related to bleeding. BC for CAO caused by blood clot or foreign body was successful in most cases, and there were no complications. CONCLUSION: BC is an efficient and relatively safe intervention for patients with CAO. Our findings suggest that diabetes, respiratory failure before BC, and the absence of distal airway atelectasis may be risk factors of moderate to severe intrabronchial bleeding.

Cryotherapy Attenuates Inflammation via the lncRNA SNHG1/miR-9-5p/NFKB1 Regulatory Axis in Periodontal Ligament Cells.

Cryotherapy is a common non-pharmacological method to relieve pain and inflammation. Clinical studies have shown that cryotherapy can reduce postoperative pain after root canal therapy, but the mechanism remains unclear. In this study, we aimed to investigate the underlying molecular mechanisms by which cryotherapy reduces inflammation in lipopolysaccharide (LPS)-stimulated periodontal ligament cells through transcriptome sequencing analysis. We found that cryotherapy significantly reduced the expression of multiple proinflammatory cytokines and chemokines, and NFKB1 was the key regulator down-regulated by cryotherapy. Importantly, we discovered that lncRNA SNHG1 expression level significantly decreased after cold treatment. SNHG1 expression was positively related to NFKB1 while negatively correlated with miR-9-5p, which formed a novel ceRNA regulatory pathway. Knockdown of SNHG1 significantly reduced the expression of NFKB1, IL1B, and IL6, while overexpression of SNHG1 significantly increased the expression of these genes. In conclusion, our study demonstrated that cryotherapy can effectively reduce inflammation in LPS-induced periodontal ligament cells by suppressing the lncRNA SNHG1/miR-9-5p/NFKB1 axis.

Ablation as First-line Therapy for Atrial Fibrillation.

AF is a chronic and progressive heart rhythm disorder characterised by exacerbations and remissions. Contemporary guidelines recommend antiarrhythmic drugs (AADs) as the initial therapy for the maintenance of sinus rhythm. However, these medications have modest efficacy and are associated with significant adverse effects. Several recent trials have evaluated catheter ablation as an initial therapy for AF, demonstrating that cryoballoon catheter ablation significantly improves arrhythmia outcomes (e.g. atrial tachyarrhythmia recurrence and arrhythmia burden), produces clinically meaningful improvements in patient-reported outcomes (e.g. symptoms and quality of life), and significantly decreases healthcare resource usage (e.g. hospitalisation), without increasing the risk of serious adverse events. Moreover, in contrast to antiarrhythmic drugs, catheter ablation appears to be disease-modifying, significantly reducing the progression of disease. These findings are relevant to patients, providers, and healthcare systems, helping inform the initial choice of rhythm-control therapy in patients with treatment-naïve AF.

Primary Total Prostate Cryoablation for Localized High-Risk Prostate Cancer: 10-Year Outcomes and Nomograms.

The role of prostate cryoablation was still uncertain for patients with high-risk prostate cancer (PC). This study was designed to investigate 10-year disease-free survival and establish a nomogram in localized high-risk PC patients. Between October 2008 and December 2020, 191 patients with high-risk PC who received primary total prostate cryoablation (PTPC) were enrolled. The primary endpoint was biochemical recurrence (BCR), defined using Phoenix criteria. The performance of pre-operative and peri-operative nomograms was determined using the Harrell concordance index (C-index). Among the cohort, the median age and PSA levels at diagnosis were 71 years and 12.3 ng/mL, respectively. Gleason sum 8-10, stage ≥ T3a, and PSA > 20 ng/mL were noted in 27.2%, 74.4%, and 26.2% of patients, respectively. During the median follow-up duration of 120.4 months, BCR-free rates at 1, 3, 5, and 10 years were 92.6%, 76.6%, 66.7%, and 50.8%, respectively. The metastasis-free, cancer-specific, and overall survival rates were 89.5%, 97.4%, and 90.5% at 10 years, respectively. The variables in the pre-operative nomogram for BCR contained PSA at diagnosis, clinical stage, and Gleason score (C-index: 0.73, 95% CI, 0.67-0.79). The variables in the peri-operative nomogram for BCR included PSA at diagnosis, Gleason score, number of cryoprobes used, and PSA nadir (C-index: 0.83, 95% CI, 0.78-0.88). In conclusion, total prostate cryoablation appears to be an effective treatment option for selected men with high-risk PC. A pre-operative nomogram can help select patients suitable for cryoablation. A peri-operative nomogram signifies the importance of the ample use of cryoprobes and helps identify patients who may need early salvage treatment.

Anesthetic Efficacy of Endo-Ice and Intrapulpal Ice Sticks After Inferior Alveolar Nerve Block in Symptomatic Irreversible Pulpitis: A Randomized Controlled Study.

BACKGROUND: There is a dearth of studies to assess the effectiveness of cryotherapy as a possible adjuvant in anesthesia. Therefore, this study aimed to compare the impact of pretreatment intraoral ice packs, application of Endo-ice, and a combination of Endo-ice and intrapulpal ice sticks use on the effectiveness of pulpal anesthesia as an adjunct in the management of pain and dental anxiety in mandibular second molars with symptomatic irreversible pulpitis (SIP) against traditional inferior alveolar nerve block (IANB) technique. MATERIALS AND METHODS: The randomized controlled double-blind clinical study comprised of 200 subjects within the age group of 20-45 years with SIP involving mandibular second molars and divided into four groups of 50 each. Conventional IANB was administered in group 1. Intraoral compact ice packs, Endo-ice, and combined use of Endo-ice and intrapulpal ice sticks were employed following conventional IANB in groups 2, 3, and 4, respectively. The intensity of pain and anxiety before and after the intervention was documented using Heft-Parker visual analog scale (HP-VAS) and Corah's Dental Anxiety Scale-Revised (DAS-R). RESULTS: The average age of the overall study sample was 30.8±2.08 years, and the differences in age and gender distribution were found to be statistically insignificant. The mean HP-VAS scores on access opening and pulpectomy, using ANOVA paired with Tukey's post hoc multiple comparison tests were evaluated to be statistically highly significant (p<0.001). The greatest reduction in HP-VAS score was observed in group 4 receiving combined use of both Endo-ice and intrapulpal ice sticks. While the pretreatment DAS-R score was determined to be statistically insignificant between groups, group 1 subjects had the highest DAS-R score postoperatively (p<0.001). The effectiveness of pulpal anesthesia was found to be 84%, 96%, 92%, and 98% for groups 1 through 4, respectively, and demonstrated a statistically significant difference. CONCLUSION: The combined use of Endo-ice and intrapulpal ice sticks used as an adjuvant to local anesthesia (LA) was found to be significantly effective in lowering pain compared to the control groups in molars with SIP. Cold administration before and during the procedure was more effective than conventional LA in lowering intraoperative anxiety. Furthermore, the use of Endo-ice and intrapulpal cold after IANB significantly improves the effectiveness of pulpal anesthesia in mandibular second molars with SIP.

Whole-Body Cryotherapy Alters Circulating MicroRNA Profile in Postmenopausal Women.

The incidence of metabolic syndrome (MetS) increases with age, especially in women. The role of microRNAs (miRs) in the regulation of metabolism is postulated. The aim of the study is to identify miRs that may be markers of MetS and to assess changes in miRs expression as a result of 10 and 20 whole-body cryotherapy treatments (WBC; 3 min, -120 °C) in postmenopausal women with MetS (M-60, BMI 30.56 ± 5.38 kg/m2), compared to healthy postmenopausal (H-60, BMI 25.57 ± 2.46 kg/m2) and healthy young women (H-20, BMI 22.90 ± 3.19 kg/m2). In a fasting state, before 1 WBC and after 10 WBCs, as well as 20 WBCs, the expression of miR-15a-5p, miR-21-5p, miR-23a-3p, miR-146a-5p, miR-197-3p, miR-223-3p, fasting blood glucose (FBG) and blood lipid profile were determined. miR-15a-5p and miR-21-5p were down-regulated in M-60, while miR-23a-3p and miR-197-3p were up-regulated, and miR-223-3p down-regulated in M-60 and H-60, compared to H-20. Significant positive correlations between up-regulated (mostly for miR-23-3p and miR-197-3p) and significant negative correlations between down-regulated (mostly for miR-15a-5p) miRs and markers of body composition as well as metabolic disorders were observed. After 20 WBCs, miR-15a-5p expression was up-regulated in all groups. In H-60, down-regulation of miR-197-3p expression occurred after 10 WBCs and 20 WBCs. Following 10 WBCs, FBG decreased in all groups, which intensified in M-60 post-20 WBCs. In our research, it has been shown that miR-23a-3p and miR-197-3p are accurate markers of MetS and MetS risk factors, while miR-15a-5p and miR-23a-3p are precise markers of body composition disorders. WBC is an effective treatment for up-regulating miR-15a-5p and lowering glucose levels in young and postmenopausal women and down-regulating miR-197-3p expression in postmenopausal women. It may be an adjunctive effective treatment method in MetS and hyperglycemia.

External Root Surface Temperature Control with 1,1,1,2-Tetrafluoroethane Intracanal Cryotherapy during Thermoplastic Obturation: An In Vitro Study.

AIM: The aim of this in vitro study was to determine the effectiveness of 1,1,1,2-tetrafluoroethane (TFE) intracanal cryotherapy for external root surface temperature control during thermoplastic obturation. MATERIALS AND METHODS: Thirty extracted adult single-rooted mandibular incisors were selected for this study. Endodontic shaping was performed until size X3 Protaper Next Rotary endodontic file. The teeth were divided into three groups: Group I-Control group wherein conventional irrigation was done using physiologic saline stored at room temperature, Group II-Irrigational Cryotherapy group using physiologic saline at 2.5°C, and Group III-Intracanal TFE cryotherapy group with intracanal refrigerant TFE application. Temperatures were recorded in the apical 3 mm before and after completion of each intervention and post thermoplastic obturation using a noncontact digital laser infrared thermometer. RESULTS: Intracanal cryotherapy with TFE resulted in a mean decrease of 9.27°C compared with conventional irrigation that exhibited in a mean decrease of 2.13°C. Also, in intracanal cryotherapy group with TFE application, compared with the baseline (24.50°C), no significant differences were observed post obturation (24.61°C) with high-temperature-injectable gutta percha technique indicating good control of temperature rise on the external root surface. CONCLUSION: Intracanal cryotherapy with refrigerant TFE was highly effective in controlling temperature rise on the external root surface during injectable thermoplastic obturation technique. CLINICAL SIGNIFICANCE: Minimizing deleterious effects due to high temperatures generated during the thermoplastic obturation is critical. Clinically feasible measures to reduce the transmission of heat generated during thermoplastic obturation have been searched since long. In this regard, intracanal cryotherapy with TFE can be effectively used to control the rise of temperature on the external root surface when employing thermoplastic obturation technique.

Protective effect of cryotherapy against oral mucositis among allogeneic hematopoietic stem cell transplant recipients using melphalan-based conditioning.

PURPOSE: Oral cryotherapy is an effective method to prevent oral mucositis (OM) induced by chemotherapeutic agents, such as melphalan (Mel). However, there is limited data about cryotherapy in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients; thus, the current study aimed to examine the efficacy of cryotherapy among allo-HSCT recipients treated with Mel-containing regimens. METHODS: Medical records of 78 consecutive allo-HSCT recipients were retrospectively analyzed. Baseline characteristics and clinical courses between the patients who received cryotherapy (cryotherapy group, n = 42) and those who did not (control group, n = 36) were compared, especially focusing on methotrexate (MTX) use as a part of graft-versus-host disease (GVHD) prophylaxis. RESULTS: Binary logistic regression analysis revealed that a higher dose of Mel (OR, 3.82; 95%CI, 1.085-13.46; P = 0.037) or MTX use (OR, 7.61; 95% CI, 2.41-23.97; P < 0.001) was associated with the incidence of OM. MTX use was also significantly associated with the duration of OM (ß = 0.515; 95% CI, 9.712-21.636; P < 0.001). Among 31 patients without MTX use, cryotherapy was associated with a significant reduction of OM development (0% in the cryotherapy group vs 35% in the control group, P = 0.021). We did not find such an association in 47 patients with MTX use. CONCLUSION: Cryotherapy was useful to prevent the incidence of OM in allo-HSCT recipients in the cases without MTX for GVHD prophylaxis.

Successful Treatment of Cutaneous Leishmaniasis With Cryotherapy.

Leishmaniasis, a protozoal infection, is a growing health concern with 1.5 million new cases reported annually resulting in a wide spectrum of disease and clinical presentations. The disease is endemic in 98 countries with increasing prevalence in non-endemic areas. There are various treatment approaches that are often individualized based on host and parasite factors. Current treatment guidelines and data are variable and provide limited direction for specific treatment plans. Additionally, current recommended therapies are not benign, and are expensive and unavailable to most patients, especially in low-resource areas where leishmaniasis is most prevalent. Here, we report the diagnosis and successful treatment of cutaneous leishmaniasis in a 65-year-old male, who recently traveled to Mexico. Initial treatment with topical antifungals and oral antibiotics was ineffective. After successive treatment with local liquid nitrogen, the lesions completely resolved with no adverse effects or recurrence. Given there is limited evidence-based data supporting cryotherapy treatment as a first-line treatment, this report supports the efficacy of cryotherapy as a safe, cost-effective, and accessible treatment for cutaneous leishmaniasis.