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.

A Population-Based Analysis of Long-Term Costs and Adverse Events after Pneumatic Retinopexy and Pars Plana Vitrectomy.

PURPOSE: To comprehensively examine the cost effectiveness, reattachment rate, and complications of pneumatic retinopexy (PnR) compared with pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD) within a universal health care system. DESIGN: Population-based, multicenter, consecutive, retrospective longitudinal cohort analysis. SUBJECTS: We identified consecutive adults aged ≥ 50 years requiring surgery for primary RRD over a 20-year interval between April 1, 2002, and March 31, 2022. Initial surgery was considered the index date for analyses. INTERVENTION: Pneumatic retinopexy was compared with PPV in all analyses. MAIN OUTCOME MEASURES: The primary analysis investigated the mean annualized health care costs comparing PnR to PPV over the 2 years after initial surgery. Secondary analyses examined the primary reattachment rate and complications. RESULTS: In total, 25 665 eligible patients were identified, with 8794 undergoing PnR and 16 871 undergoing PPV. The mean patient age was 65 years and 39% were women. The mean annualized cost after PnR was $8924 and $11 937 after PPV (mean difference, $3013; 95% confidence interval, $2533-$3493; P < 0.001). The primary reattachment rate at 90 days after PnR was 83% and after PPV was 93% (P < 0.001). The risk of cataract or glaucoma surgery was lower after PnR, and the frequency of ophthalmology clinic visits, intravitreal injections, and anxiety was higher after PnR. Hospitalizations and long-term disability were less frequent after PnR. CONCLUSIONS: Pneumatic retinopexy, when compared with PPV, was associated with lower long-term health care costs. Pneumatic retinopexy appeared to be effective, safe, and inexpensive, thus offering a viable option for improving access to RRD repair in appropriately selected cases. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Assessment of the Efficacy of Cryolipolysis on Abdominal Fat Deposits: A Prospective Study.

BACKGROUND: Cryolipolysis is a non-invasive and efficacious procedure for body contouring. The effectiveness of cryolipolysis has been demonstrated on multiple areas of the body, but on a limited number of subjects. The aim of this study is to demonstrate the effectiveness and the safety of cryolipolysis in the lower abdomen adipose tissue thickness reduction. METHODS: A prospective study on 60 healthy women was carried out using CryoSlim Hybrid device. Each patient underwent two cryolipolysis sessions centered on the abdominal area. The primary endpoint was to decrease the thickness of the abdominal fat deposits. The change in the abdominal circumference and the thickness of the subcutaneous fat layer were assessed. Patient satisfaction and tolerance of the procedure were also taken into account. RESULTS: A significant reduction of the abdominal circumference and subcutaneous fat layer thickness was observed. The mean decrease in abdominal circumference was 2.10 cm (3.1%) 3 months after the procedure and 4.03 cm (5.8%) 6 months after the procedure. The mean decrease in fat layer thickness was 1.25 cm (43.81%) 3 months after the procedure and 1.61 cm (41.73%) 6 months after the procedure. No major adverse events were noted. All patients were very satisfied, and minimal pain was reported. CONCLUSIONS: Cryolipolysis is an effective technique to treat abdominal localized fat deposits. No major adverse events have been described for this procedure. Our promising results should encourage further studies aimed at optimizing the efficacy of the procedure without a considerable increase in the risks. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Cryothérapie et prévention des neuropathies périphériques induites par l'administration des taxanes / Cryotherapy for the prevention of taxane-induced peripheral neuropathy

INTRODUCTION: Plusieurs tumeurs solides sont traitées par des molécules de chimiothérapie, y compris celles appartenant à la famille des taxanes. Ces molécules peuvent provoquer des effets secondaires non négligeables, particulièrement des symptômes de neuropathie des nerfs périphériques induits par la chimiothérapie (NPIC). Ces symptômes se traduisent par des troubles de la sensibilité et des troubles moteurs ainsi que des douleurs aux membres supérieurs et inférieurs. L'impact est important sur la qualité de vie des patients. L'incidence des symptômes de neuropathie des nerfs périphériques se situe entre 30 et 70 % selon la molécule de chimiothérapie administrée, et aucun traitement médical préventif n'a montré d'efficacité à les prévenir ou à les traiter. Certaines équipes de soins en oncologie recourent à des interventions non pharmacologiques pour prévenir les effets neurotoxiques de la chimiothérapie. La cryothérapie, l'une des méthodes employées, consiste à refroidir les mains et les pieds par l'entremise de mitaines refroidies durant les perfusions de chimiothérapie, notamment de taxanes. Le but de cette intervention est de réduire la quantité du flux sanguin aux extrémités et ainsi de prévenir la neurotoxicité. La Direction adjointe du Programme québécois de cancérologie (PQC) et la Direction générale des affaires universitaires, médicales, infirmières et pharmaceutiques (DGAUMIP) du ministère de la Santé et des Services sociaux (MSSS) ont demandé à l'Institut national d'excellence en santé et en services sociaux (INESSS) de produire un état des connaissances et d'indiquer la position respective des sociétés savantes sur l'efficacité et l'innocuité de la cryothérapie pour prévenir les neuropathies périphériques induites par les taxanes. MÉTHODOLOGIE: Afin de répondre à ce mandat, une recherche de la littérature scientifique et grise a été effectuée en ciblant les revues systématiques, avec ou sans méta-analyse, les études primaires (essais cliniques à répartition aléatoire ou non), les études de cohortes ainsi que les guides de pratique clinique. Les résumés de conférences ainsi que les études narratives ont été exclus. Les constats retenus ont été présentés et discutés avec le Comité d'évolution des pratiques en oncologie (CEPO) du ministère de la Santé et des Services sociaux et ont ensuite été révisés par des lecteurs externes. PRINCIPAUX CONSTATS: En se basant sur la documentation scientifique disponible au moment de la rédaction et sur les consultations menées, les constats suivants sont formulés. Contexte et besoin de santé: La toxicité des nerfs périphériques induite par la chimiothérapie est un phénomène fréquent qui touche de 30 à 70 % des patients qui reçoivent une chimiothérapie. Elle se traduit par des paresthésies et parfois des troubles moteurs (troubles de la dextérité, crampes, faiblesse musculaire) qui peuvent être majeurs chez quelques patients. Certains d'entre eux peuvent avoir des séquelles à long terme. La sévérité de ces symptômes a un impact considérable sur la qualité de vie des personnes traitées par la chimiothérapie, y compris par les taxanes. Elle peut même conduire à la réduction des doses de chimiothérapie requises, au retard ou à l'arrêt du traitement oncologique. Neurotoxicité et cryothérapie: Le paclitaxel et le docétaxel sont deux molécules appartenant à la famille des taxanes qui ont un potentiel neurotoxique élevé. Elles sont fréquemment administrées pour traiter de nombreux types de tumeurs solides. L'utilisation de la cryothérapie pour prévenir la neurotoxicité s'inspire des résultats positifs obtenus par l'usage de casques réfrigérants en prévention de l'alopécie durant l'administration de certaines chimiothérapies et par l'utilisation du froid (mitaines et chaussettes réfrigérantes) pour réduire la toxicité unguéale. Sur ce même principe, des équipes de cliniciens de plusieurs pays utilisent des dispositifs, notamment des gants et des chaussettes réfrigérés, appliqués aux extrémités durant les cycles de traitement oncologique dans le but de prévenir les effets toxiques de la chimiothérapie au niveau des nerfs périphériques. Appréciation du niveau de la preuve Scientifique: Les publications de bonne qualité méthodologique sur le sujet sont peu nombreuses. Onze ont été retenues, dont cinq sont à répartition aléatoire, sans insu et portant sur un faible nombre de patients. Les objectifs visés par la cryothérapie ont été faiblement atteints dans les études recensées, et la significativité clinique de la preuve scientifique est incertaine. Les études rapportées sont entachées de nombreuses limites méthodologiques pouvant mener à un risque de biais très élevé, ce qui rend difficile l'interprétation des résultats : manque de cohérence, de crédibilité et de fiabilité. Efficacité et innocuité: Les données disponibles, provenant d'études de qualité méthodologique faible, ne permettent pas de conclure à propos de: -l'efficacité de la cryothérapie pour prévenir les neuropathies périphériques induites par la chimiothérapie; - l'innocuité de la cryothérapie ainsi que la tolérance des patients à l'égard de ce traitement préventif, lequel exige d'être exposé au froid parfois pendant la durée de l'administration. Par contre, les effets secondaires associés à la cryothérapie semblent peu fréquents et de faible intensité dans les quelques études qui les ont évalués. Bien qu'aucune étude n'ait rapporté de cas d'engelure, l'intolérance au froid a été signalée dans six études sur onze et a causé plusieurs cas d'attrition. Il n'a pas été observé d'arrêt de la cryothérapie dans les autres études. La plupart des auteurs mentionnent qu'il serait important de faire des études méthodologiquement plus robustes pour bien évaluer l'efficacité et l'innocuité de la cryothérapie pour la prévention des neuropathies périphériques (NP) induites par les taxanes. Lignes directrices et études en cours: Le seul guide de pratique clinique repéré indique qu'aucune recommandation ne peut être formulée quant à l'usage de diverses options pharmacologiques et non pharmacologiques de prévention des neuropathies des nerfs périphériques, y compris la cryothérapie, en raison de la faible qualité méthodologique des études retenues. Les auteurs de ce guide ajoutent toutefois que, même si la preuve n'est pas faite, les données disponibles suggèrent que la cryothérapie pourrait en partie prévenir les symptômes de neuropathie et que son usage paraît raisonnablement sécuritaire. Perspective des cliniciens et experts: Les cliniciens et les experts consultés reconnaissent : ­ l'important besoin de prévenir les symptômes de neuropathie induite par les taxanes; ­ l'absence de preuves scientifiques concluantes quant à l'efficacité de la cryothérapie en raison du nombre limité d'études disponibles et de la faible qualité méthodologique de celles-ci; ­ la nécessité de disposer d'études de meilleure qualité avant de pouvoir prendre position sur la question. Bien que les résultats observés soient mitigés, certains experts estiment que la cryothérapie représente tout de même un traitement préventif prometteur, puisqu'elle n'induit que peu ou pas d'effets secondaires et que son arrêt à tout moment est possible sans compromettre l'efficacité du traitement oncologique. MISE À JOUR DE L'ÉTAT DES CONNAISSANCES: La pertinence de mettre à jour le présent état des connaissances sera évaluée et déterminée en fonction des résultats de certains essais cliniques en cours à ce sujet. Les résultats de ces derniers devront paraître à partir de 2023-2024. Une mise à jour pourrait être requise advenant un apport significatif de nouvelles données disponibles à l'une ou l'autre des dimensions examinées dans cet état des connaissances.

INTRODUCTION: Many solid tumours are treated with chemotherapy drugs, including those in the taxane family. These drugs can have significant adverse effects, especially symptoms of chemotherapy-induced peripheral neuropathy (CIPN). These symptoms manifest as sensory and motor disorders and as pain in the upper and lower limbs. The symptoms are associated with poorer quality of life. The incidence of peripheral neuropathy symptoms ranges from 30% to 70%, depending on the chemotherapy drug administered, and no prophylactic medical treatment has been shown to be effective in preventing or treating them. Some cancer care teams use non-pharmacological measures to prevent the neurotoxic effects of chemotherapy. One of the methods used, cryotherapy, involves cooling the hands and feet with frozen gloves and socks during chemotherapy infusions, particularly taxanes. The goal of this measure is to reduce the amount of blood flow to the extremities and thus prevent neurotoxicity. The assistant director of the Québec Cancer Program (PQC) and the Direction générale des affaires universitaires, médicales, infirmières et pharmaceutiques (DGAUMIP) of the Ministère de la Santé et des Services sociaux (MSSS) asked the Institut national d'excellence en santé et en services sociaux (INESSS) to produce a state-of-knowledge report and to indicate the learned societies' respective positions regarding the efficacy and safety of cryotherapy for the prevention of taxane-induced peripheral neuropathy. METHODOLOGY: For the purpose of this mandate, a search of the scientific and grey literature was conducted, targeting systematic reviews, with or without meta-analysis, primary studies (randomized or non-randomized clinical trials), cohort studies, and clinical practice guidelines. Conference abstracts and narrative studies were excluded. The selected findings were presented and discussed with the Comité d'évolution des pratiques en oncologie (CEPO) and were then reviewed by external reviewers. MAIN FINDINGS: Based on the scientific literature available at the time of writing and on the consultations conducted, the following findings are noted: Context and health need: Chemotherapy-induced peripheral neurotoxicity is a common phenomenon affecting 30% to 70% of patients receiving chemotherapy. It manifests as paresthesia and sometimes motor disorders (manipulative dexterity problems, cramps and muscle weakness), which can be significant. Some patients can experience long-term sequelae. The severity of these symptoms can have a considerable impact on the quality of life of patients receiving chemotherapy, including taxanes. It can even lead to a reduction in the required chemotherapy doses or to a delay in or the discontinuation of cancer treatment. Neurotoxicity and cryotherapy: Paclitaxel and docetaxel are two drugs in the taxane family with a high neurotoxic potential. They are often administered to treat many types of solid tumours. The use of cryotherapy to prevent neurotoxicity is inspired by the positive results obtained with the use of cold caps to prevent alopecia after chemotherapies treatment and with the use of cold (frozen gloves and socks) to reduce nail toxicity. Based on this same principle, teams of clinicians in several countries are using devices, such as frozen gloves and socks, placed on the extremities during cancer treatment cycles to prevent the toxic effects of chemotherapy on the peripheral nerves. Assessment of the level of scientific evidence: There are few publications of good methodological quality on the subject. Eleven were selected, five of which were randomized and unblinded and involved small numbers of patients. The objectives of cryotherapy were poorly achieved in the studies identified, and the clinical significance of the scientific evidence is uncertain. The reported studies have numerous methodological limitations that can lead to a very high risk of bias, which makes it difficult to interpret the results: a lack of consistency, credibility and reliability. Efficacy and safety: The available data, which are from studies of low methodological quality, do not permit any conclusions regarding: The efficacy of cryotherapy in preventing chemotherapy-induced peripheral neuropathy; ­ The safety of cryotherapy or patients' tolerance of this preventive treatment, which requires exposure to cold, sometimes for the entire duration of administration. Otherwise, the adverse effects associated with cryotherapy appear to be infrequent and mild in the few studies that have assessed them. Although no studies reported any cases of frostbite, cold intolerance was reported in six of eleven studies and caused several cases of attrition. No cases of cryotherapy discontinuation were observed in the other studies. Most authors mention that more methodologically robust studies are needed to properly evaluate the efficacy and safety of cryotherapy for the prevention of taxane-induced peripheral neuropathy (PN). Guidelines and ongoing studies: The only clinical practice guideline found states that no recommendation can be made regarding the use of various pharmacological and non-pharmacological options for preventing peripheral neuropathy, including cryotherapy, because of the low methodological quality of the selected studies. However, the authors of the guideline add that, while this has not been proven, the available data do suggest that cryotherapy may partially prevent neuropathy symptoms and that its use appears to be reasonably safe. Perspective of clinicians and experts: The clinicians and experts consulted recognize: The important need to prevent symptoms of taxane-induced neuropathy; The lack of conclusive scientific evidence for the efficacy of cryotherapy due to the limited number of studies available and their low methodological quality; Although the results observed are mixed, some experts feel that cryotherapy is a promising preventive treatment, since it has few or no major adverse effects and can be stopped at any time without compromising the effectiveness of the cancer treatment. The need for better-quality studies before a position can be taken on the matter. UPDATE OF THIS STATE-OF-KNOWLEDGE REPORT: The advisability of updating this state-of-knowledge report will be assessed and determined on the basis of the results of certain ongoing clinical trials on this topic. The results of these trials are expected to be published starting in 2023-2024. An update may be necessary if there is a significant amount of new available data for any of the aspects examined in this state-of-knowledge report.

Cost-utility study of home-based cryotherapy device for wart treatment: a randomized, controlled, and investigator-blinded trial.

BACKGROUND: Cryotherapy is typically performed by physicians. No cost-utility studies of home-based cryotherapy have been reported. OBJECTIVES: To study the cost utility of home-based cryotherapy devices and in-hospital liquid nitrogen therapy for cutaneous warts. MATERIALS AND METHODS: This randomized, controlled, investigator-blinded trial was carried out on patients with cutaneous warts. Participants were randomly assigned to two groups: home-based cryotherapy and in-hospital liquid nitrogen therapy. Clinical examinations were conducted at baseline and monthly until cure, and outcomes (cure rate, side effects, total costs, and quality of life) were compared. A cost-utility analysis was performed. RESULTS: Nineteen of 22 patients completed the treatment and were analyzed. The efficacy of home-based cryotherapy and in-hospital therapy was 72.8% and 64.3%, respectively. Side effects (pain, redness, and burning) were observed. The mean numbers of medical visits were 2.83 for home-based therapy and 3.30 for in-hospital therapy. The total costs for home-based therapy and the in-hospital therapy were US $76.03 and $100.45, respectively. The home-based therapy had 0.2297 quality-adjusted life years, slightly higher than the corresponding value of 0.2254 for in-hospital therapy. CONCLUSIONS: Home-based cryotherapy devices are a cost-saving strategy with similar efficacy to in-hospital liquid nitrogen therapy.

Assessment of sinecatechins 10% ointment used as proactive sequential therapy in recurrence rate of genital warts lesions after cryotherapy. The PACT-II Trial (postablation immunomodulator treatment of condylomata with sinecatechins): a prospective assessor-blinded, multicenter, pilot trial.

BACKGROUND: Cryotherapy is commonly used as ablative treatment of external genital warts (EGW). However, after cryotherapy recurrence of lesions affects on average 45% (42-70%) of subjects in the 6 months after the treatment. Sinecatechins 10% are an effective topical treatment of EGW. A low recurrence rate (<6%) was observed in pivotal phase 3 trials conducted with this product. Topical sinecatechins have demonstrated to significantly reduce the recurrence rate of EGW in subjects treated with laser therapy (The PACT-I trial). So far, no prospective data are available regarding the efficacy of sinecathechins as immunomodulator sequential therapy after cryotherapy in EGW subjects. The purpose of this study was to assess the rate of recurrence lesions after the use of topical sinecatechins 10%, as sequential proactive immunomodulation treatment after cryotherapy in subjects with EGW (The PACT-II Trial: the postablation immunomodulator treatment of condylomata with sinecatechins trial) (Trial Registration number: ISRCTN44037479). METHODS: In a prospective, assessor-blinded, multicenter trial a total of 55 subjects with a diagnosis of multiple EGW (36 men and 19 women, mean age 47±10 years) and a mean lesion number of 9±7, after their informed consent, were enrolled in the study. All subjects were treated with cryotherapy (an average of 2 sessions). After the ablative treatment, all subjects were instructed to apply sinecatechin 10% ointment 3 times daily for 4 consecutive months. The primary study endpoint was the evaluation (assessor-blinded) of recurrent lesions after 6 months (2 month of follow-up after the conclusion of topical treatment). The secondary study endpoints were the appearance of new EGW lesions (lesions affecting area not treated by cryotherapy) and the local tolerability. RESULTS: At baseline, the mean number of EGW lesions were 9±7. After cryotherapy, the mean lesions number were reduced to 1.6±1.8. At month 4, EGW mean lesion number were 0.2±0.4 (P=0.0001 vs. after cryotherapy). At month 6, recurrence of lesions was detected in 10 subjects (18%; 95% CI: 9-30%) with an average of 1.4 lesions. Of these recurrent lesions, 6 occurred in completely healed lesions site after cryotherapy and 8 in partially healed ones. New lesions (outside the cryotherapy treated area) were observed in 10 subjects. The product was very well tolerated. No serious side effects were reported. Three subjects reported moderate skin irritation on the application site. CONCLUSIONS: The PACT-II Trial has shown that the recurrence rate of EGW lesions after successful cryotherapy using sinecatechins as immunomodulator sequential therapy is lower in comparison with the percentage documented in the literature without sequential therapy (20 vs. 45%). These results are in line with already published data evaluating the role of sinecatechins after laser therapy (PACT-I trial). Future comparative, double-blind controlled trials assessing the efficacy of different proactive strategies are warranted.

Shall we use cryotherapy in the treatment in surgical procedures, in acute pain or injury, or in long term pain or dysfunction? - A systematic review.

PURPOSE: This review aimed to evaluate the certainty of evidence for the use of cryotherapy in patients with musculoskeletal disorders. METHODS: PubMed, Embase, Cochrane Library and AMED were searched from January 2000 to January 2018 (update June 2019) for systematic reviews (SRs) and randomized controlled trials (RCTs) reporting outcomes on pain, swelling, range of motion (ROM), function, blood loss, analgesic use, patient satisfaction and adverse advents. The papers were categorised into: surgical procedures, acute pain or injury and long-term pain or dysfunction. Methodological quality and risk of bias were assessed using the AMSTAR and the Swedish Health Technology Assessment instruments. Level of certainty of evidence was synthesized using GRADE. STUDY SELECTION: Eight SRs and 50 RCTs from a total of 6027 (+839) were included. In total 34 studies evaluated cryotherapy in surgical procedures, twelve evaluated cryotherapy use in acute pain or injury and twelve studies evaluated cryotherapy in long-term pain and dysfunction. RESULTS: The certainty of evidence is moderate (GRADE III) after surgical procedures to reduce pain, improve ROM, for patient satisfaction and few adverse events are reported. Cryotherapy in acute pain and injury or long-term pain and dysfunction show positive effects but have a higher number of outcomes with low certainty of evidence (GRADE II). CONCLUSION: Cryotherapy may safely be used in musculoskeletal injuries and dysfunctions. It is well tolerated by patients. More advanced forms of cryotherapy may accentuate the effect. Future research is needed where timing, temperature for cooling, dose (time) and frequency are evaluated.

Assessment of the Dynamics of Temperature Changes in the Knee Joint Area in Response to Selected Cooling Agents in Thermographic Tests.

Although local cryotherapy (LC) is performed with various cooling agents (CAg) such as ice, water, and gasses, in clinical practice, it is mostly performed with cooling gasses. Presently, LC with cooling gasses is very popular but the inference about the thermal (stimulus) effect on the tissues is mainly based on research carried out using ice packs. The proposed objective of the study was to evaluate the dynamics of temperature changes in the knee joint area in response to a 3-min exposure to liquid nitrogen vapors (LNVs), cold air (CA) and ice bag (IB). The study group included 23 healthy volunteers with an average age of 26.67 ± 4.56. The exposed (ROIE) and contralateral (ROINE) areas of the knee joint after exposure to CAg were observed. Immediately after 3 min of LC, the ROIE temperature dropped by 10.11 ± 0.91 °C after LNV, 7.59 ± 0.14 °C after IB and 6.76 ± 1.3 °C after CA. Significant tissue cooling was maintained up to 15 min after LNV (p < 0.01), 10 min after IB (p < 0.05) and 5 min after CA (p < 0.05). LC causes significant temperature changes both in ROIE and ROINE. The greatest cooling potential was demonstrated for LNV and the lowest for CA.

Comparative assessment of interventions for treating cutaneous leishmaniasis: A network meta-analysis of randomized clinical trials.

INTRODUCTION: Various interventions including laser therapy, heat therapy, and several drugs have been trialed in patients with cutaneous leishmaniasis. Due to the lack of an evidence-based comparison of all these interventions, we carried out the present network meta-analysis. METHODS: Electronic databases were searched for randomized clinical trials evaluating the efficacy and safety of any interventions in patients with cutaneous leishmaniasis. The proportion of patients with complete cure was the primary outcome. The proportion of lesions cured at the end of treatment, the proportion of lesions with minimal/no response to treatment, and proportion of wounds with minimal/no change were the secondary outcomes. Random-effects modeling was used for generating pooled estimates. Rankogram plot was used for identifying the 'best intervention'. For interventions containing a combination of treatments, backslash (/) has been used for depicting the same. RESULTS: One-hundred and thirty-one studies were included. Intralesional meglumine, topical paromomycin/gentamicin, topical paromomycin, parenteral sodium stibogluconate, topical honey/intralesional meglumine, topical liposomal amphotericin B, oral zinc sulphate, oral miltefosine, parenteral meglumine, heat therapy, topical liposomal azithromycin, intralesional meglumine/silver dressing, intralesional sodium stibogluconate, parenteral meglumine/intralesional meglumine, oral allopurinol/parenteral meglumine, topical trichloroacetic acid/heat therapy, oral zinc sulphate/oral ketoconazole, topical imiquimod/cryotherapy, intralesional meglumine/cryotherapy, topical herbal extract of Z-HE, parenteral pentamidine, topical trichloroacetic acid/intralesional meglumine, carbon-dioxide laser, topical recombinant granulocyte-macrophage colony-stimulating factor/parenteral meglumine, intralesional dapsone, carbon-dioxide laser/intralesional meglumine, moist wet dressing with sodium hypochlorite, parenteral sodium stibogluconate/intralesional recombinant granulocyte-macrophage colony-stimulating factor, oral dapsone, intralesional sodium stibogluconate/oral ketoconazole, intralesional sodium stibogluconate/parenteral sodium stibogluconate and electrocautery/moist wet dressing with sodium hypochlorite were observed with significantly greater proportion of patients with complete cure compared to placebo/untreated controls. Rankogram analysis revealed that parenteral pentamidine has the highest statistical probability of being the best in the pool. CONCLUSION: We observed several interventions to be effective for treating cutaneous leishmaniasis. However, greater caution is required in interpreting the results as the estimates are likely to change with the advent of results from future studies.

A Non-Surgical and Cost-Effective Treatment Approach Employing Topical Imiquimod, 5-Fluorouracil, and Tretinoin for Primary Non-Melanoma Skin Cancers.

BACKGROUND: Minimally invasive alternative approaches to treat non-melanoma skin cancers remain limited and unproven. OBJECTIVE: We aim to assess the efficacy of varying combinations of anti-tumor agents—imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream—with brief cryotherapy in treating non-melanoma skin cancers. METHODS: This retrospective study included 690 cases of non-melanoma skin cancers in 480 patients who received a diagnosis of a basal cell carcinoma or squamous cell carcinoma during a ten-year period. During treatment period, patients applied 30 applications of one of three combinations (imiquimod/tretinoin, 5-fluorouracil/tretinoin, or imiquimod/5-fluorouracil/tretinoin) and had cryotherapy every 2 weeks. Each patient had a clinical examination at least three years post-treatment or documented treatment failure. Clearance was defined by a lack of persistence or recurrence for 3 years following the completion of treatment. The likelihood of lesion clearance was evaluated using multivariable logistic regression analysis. RESULTS: A total of 186 cases (97; basal cell carcinoma and 89; squamous cell carcinoma) in 133 patients [37% women and 63% men; median (interquartile range) age, 77 (69, 83) years] met the inclusion criteria. Multivariable logistic regression analysis adjusting for clinical and lesion variables demonstrated that, relative to the imiquimod/5-fluorouracil/tretinoin treatment approach, imiquimod/ tretinoin (odds ratio, 0.05; 95% confidence interval, 0.00-0.99) and 5-fluorouracil/tretinoin (0.02; 0.00–0.45) were associated with lower likelihoods of lesion clearance. Likewise, morpheaform basal cell carcinoma had a lower probability of clearance (0.05; 0.00–0.72). CONCLUSIONS: The combination of imiquimod/5-fluorouracil/tretinoin with cryotherapy had high clearance rates and was the most effective treatment regimen. J Drugs Dermatol. 2021;20(3):260-267. doi:10.36849/JDD.5427.

Quantifiable Contrast-Enhanced Ultrasound Explores the Role of Protection, Rest, Ice (Cryotherapy), Compression and Elevation (PRICE) Therapy on Microvascular Blood Flow.

The aim of this randomized controlled laboratory study was to evaluate the role of standardized protection, rest, ice (cryotherapy), compression and elevation (PRICE) therapy on microvascular blood flow in human skeletal muscle. Quantifiable contrast-enhanced ultrasound was used to analyze intramuscular tissue perfusion (ITP) of the rectus femoris (RF) and vastus intermedius (VI) muscles in 20 healthy athletes who were randomly assigned to PRICE or control groups. Baseline perfusion measurements (resting conditions, T0) were compared with cycling exercise (T1), intervention (PRICE or control, T2) and follow-up at 60 min post-intervention (T3). The 20 min PRICE intervention included rest, cryotherapy (3°C), compression (35 mm Hg) and elevation. After intervention, PRICE demonstrated a decrease of ITP in VI (-47%, p = 0.01) and RF (-50%, p = 0.037) muscles. At T3, an ongoing decreased ITP for the RF (p = 0.003) and no significant changes for the VI were observed. In contrast, the control group showed an increased ITP at T2 and no significant differences at T3. PRICE applied after exercise led to a down-regulation of ITP, and the termination of PRICE does not appear to be associated with a reactive hyperemia for at least 60 min after treatment.

Assessment of Return to Baseline Urinary and Sexual Function Following Primary Focal Cryotherapy for Nonmetastatic Prostate Cancer.

BACKGROUND: The oncological outcomes in men with clinically significant prostate cancer following focal cryotherapy are promising, although functional outcomes are under-reported. OBJECTIVE: To determine the impact of focal cryotherapy on urinary and sexual function, specifically assessing return to baseline function. DESIGN, SETTING, AND PARTICIPANTS: Between October 2013 and November 2016, 58 of 122 men who underwent focal cryotherapy for predominantly anterior clinically significant localised prostate cancer within a prospective registry returned patient-reported outcome measure questionnaires, which included International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-15) questionnaires. INTERVENTION: Standard cryotherapy procedure using either the SeedNet or the Visual-ICE cryotherapy system. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome was return to baseline function of IPSS score and IIEF erectile function (EF) subdomain. Cumulative incidence and Cox-regression analyses were performed. RESULTS AND LIMITATIONS: Probability of returning to baseline IPSS function was 78% at 12 mo and 87% at both 18 and 24 mo, with recovery seen up to 18 mo. For IIEF (EF domain), the probability of returning to baseline function was 85% at 12 mo and 89% at both 18 and 24 mo, with recovery seen up to 18 mo. Only the preoperative IIEF-EF score was associated with a poor outcome (hazard ratio 0.96, 95% confidence interval 0.93-0.999, p = 0.04). The main limitation was that only half of the patients returned their questionnaires. CONCLUSIONS: In men undergoing primary focal cryotherapy, there is a high degree of preservation of urinary and erectile function with return to baseline function occurring from 3 mo and continuing up to 18 mo after focal cryotherapy. PATIENT SUMMARY: In men who underwent focal cryotherapy for prostate cancer, approximately nine in 10 returned to their baseline urinary and sexual function. Keeping in mind that level 1 evidence and long-term data are still needed, in men who wish to preserve urinary and sexual function, focal cryotherapy may be considered an alternative treatment option to radical therapy.

Energy Expenditure and Macronutrient Oxidation in Response to an Individualized Nonshivering Cooling Protocol.

OBJECTIVE: This study aimed to describe the energy expenditure (EE) and macronutrient oxidation response to an individualized nonshivering cold exposure in young healthy adults. METHODS: Two different groups of 44 (study 1: 22.1 [SD 2.1] years old, 25.6 [SD 5.2] kg/m2 , 34% men) and 13 young healthy adults (study 2: 25.6 [SD 3.0] years old, 23.6 [SD 2.4] kg/m2 , 54% men) participated in this study. Resting metabolic rate (RMR) and macronutrient oxidation rates were measured by indirect calorimetry under fasting conditions in a warm environment (for 30 minutes) and in mild cold conditions (for 65 minutes, with the individual wearing a water-perfused cooling vest set at an individualized temperature adjusted to the individual's shivering threshold). RESULTS: In study 1, EE increased in the initial stage of cold exposure and remained stable for the whole cold exposure (P < 0.001). Mean cold-induced thermogenesis (9.56 ± 7.9 kcal/h) was 13.9% ± 11.6% of the RMR (range: -14.8% to 39.9% of the RMR). Carbohydrate oxidation decreased during the first 30 minutes of the cold exposure and later recovered up to the baseline values (P < 0.01) in parallel to opposite changes in fat oxidation (P < 0.01). Results were replicated in study 2. CONCLUSIONS: A 1-hour mild cold exposure individually adjusted to elicit maximum nonshivering thermogenesis induces a very modest increase in EE and a shift of macronutrient oxidation that may underlie a shift in thermogenic tissue activity.

Assessment of the Influence Systemic Cryotherapy Exerts on Chosen Skin Scores of Patients with Atopic Dermatitis: Pilot Study.

BACKGROUND: One of the most important tasks in the treatment of atopic dermatitis (AD) is alleviation of racking skin dryness and persistent pruritus, because these factors exert a significant influence on worsening patients' quality of life. Cryotherapy being a new form of rehabilitation in AD may supplement and support a long-term process of AD treatment, because it has anti-inflammatory and antipruritic effects and exerts a positive influence on the nervous system. METHODS: 14 adults (mean age 32 ± 10.8) with mild to moderate AD were enrolled. WBC (15 treatments in total) took place in winter 2018/2019. Patient skin parameters (hydration of the epidermis, sebum level, and skin pH level) were measured with probes produced by Courage + Khazaka Electronic GmbH. RESULTS: Changes were observed in the hydration level of the epidermis. The SCORAD index evaluating the AD intensity level also changed (decreased). CONCLUSION: Due to these properties, hypothesis has been put forward that WBC can be an effective, supporting method in the treatment of AD.

Systems-level barriers to treatment in a cervical cancer prevention program in Kenya: Several observational studies.

OBJECTIVE: To identify health systems-level barriers to treatment for women who screened positive for high-risk human papillomavirus (hrHPV) in a cervical cancer prevention program in Kenya. METHODS: In a trial of implementation strategies for hrHPV-based cervical cancer screening in western Kenya in 2018-2019, women underwent hrHPV testing offered through community health campaigns, and women who tested positive were referred to government health facilities for cryotherapy. The current analysis draws on treatment data from this trial, as well as two observational studies that were conducted: 1) periodic assessments of the treatment sites to ascertain availability of resources for treatment and 2) surveys with treatment providers to elicit their views on barriers to care. Bivariate analyses were performed for the site assessment data, and the provider survey data were analyzed descriptively. RESULTS: Seventeen site assessments were performed across three treatment sites. All three sites reported instances of supply stockouts, two sites reported treatment delays due to lack of supplies, and two sites reported treatment delays due to provider factors. Of the 16 providers surveyed, ten (67%) perceived lack of knowledge of HPV and cervical cancer as the main barrier in women's decision to get treated, and seven (47%) perceived financial barriers for transportation and childcare as the main barrier to accessing treatment. Eight (50%) endorsed that providing treatment free of cost was the greatest facilitator of treatment. CONCLUSION: Patient education and financial support to reach treatment are potential areas for intervention to increase rates of hrHPV+ women presenting for treatment. It is also essential to eliminate barriers that prevent treatment of women who present, including ensuring adequate supplies and staff for treatment.

Simulated accuracy assessment of small footprint body-mounted probe alignment device for MRI-guided cryotherapy of abdominal lesions.

PURPOSE: Magnetic resonance imaging (MRI)-guided percutaneous cryotherapy of abdominal lesions, an established procedure, uses MRI to guide and monitor the cryoablation of lesions. Methods to precisely guide cryotherapy probes with a minimum amount of trial-and-error are yet to be established. To aid physicians in attaining precise probe alignment without trial-and-error, a body-mounted motorized cryotherapy-probe alignment device (BMCPAD) with motion compensation was clinically tested in this study. The study also compared the contribution of body motion and organ motion compensation to the guidance accuracy of a body-mounted probe alignment device. METHODS: The accuracy of guidance using the BMCPAD was prospectively measured during MRI-guided percutaneous cryotherapies before insertion of the probes. Clinical parameters including patient age, types of anesthesia, depths of the target, and organ sites of target were collected. By using MR images of the target organs and fiducial markers embedded in the BMCPAD, we retrospectively simulated the guidance accuracy with body motion compensation, organ motion compensation, and no compensation. The collected data were analyzed to test the impact of motion compensation on the guidance accuracy. RESULTS: Thirty-seven physical guidance of probes were prospectively recorded for sixteen completed cases. The accuracy of physical guidance using the BMCPAD was 13.4 ± 11.1 mm. The simulated accuracy of guidance with body motion compensation, organ motion compensation, and no compensation was 2.4 ± 2.9 mm, 2.2 ± 1.6 mm, and 3.5 ± 2.9 mm, respectively. Data analysis revealed that the body motion compensation and organ motion compensation individually impacted the improvement in the accuracy of simulated guidance. Moreover, the difference in the accuracy of guidance either by body motion compensation or organ motion compensation was not statistically significant. The major clinical parameters impacting the accuracy of guidance were the body and organ motions. Patient age, types of anesthesia, depths of the target, and organ sites of target did not influence the accuracy of guidance using BMCPAD. The magnitude of body surface movement and organ movement exhibited mutual statistical correlation. CONCLUSIONS: The BMCPAD demonstrated guidance accuracy comparable to that of previously reported devices for CT-guided procedures. The analysis using simulated motion compensation revealed that body motion compensation and organ motion compensation individually impact the improvement in the accuracy of device-guided cryotherapy probe alignment. Considering the correlation between body and organ movements, we also determined that body motion compensation using the ring fiducial markers in the BMCPAD can be solely used to address both body and organ motions in MRI-guided cryotherapy.

Intralesional immunotherapy with purified protein derivative (PPD) for cryotherapy-resistant warts.

BACKGROUND: Cryotherapy and immunotherapeutic modalities elicit nonspecific immune response against the human papillomavirus. There is a paucity of literature on the effects of a sequential shift to immunotherapy in cryotherapy-resistant warts. AIM: To study the efficacy of intralesional purified protein derivative (PPD) immunotherapy in cryotherapy-resistant warts. METHODS: Patients with cryotherapy-recalcitrant cutaneous warts were given intralesional injections of PPD into the index warts (oldest or largest) at 2-week intervals until complete clearance or up to a maximum of six injections. The response in the treated index and distant warts was defined as complete, partial, and no response (<25%). Complete responders were followed up for another 3 months to check for recurrence. RESULTS: Twenty-eight patients completed the study protocol. Of the eight patients with single warts, four (50%), one (12.5%), and three (37.5%) patients had complete, partial, and no response, respectively. Of the 20 patients with multiple warts, nine (45%) had complete clearance of all warts, two (10%) each had complete and partial response in the index wart, respectively, with no response of the distant warts, and seven (35%) had no response in all warts. Complete response was seen in an average of 3.1 injections (range 1-5). There was no recurrence at the follow-up visit. CONCLUSION: Immunotherapy with PPD has potential in producing regional and remote wart regression even in cryotherapy-resistant warts. It is a safe and economical modality in children, multiple warts, and difficult-to-treat warts.