Wounds : a compendium of clinical research and practice最新文献

{"title":"A multicenter hybrid platform trial evaluating amniotic tissue grafts in chronic wounds: a real-world evidence protocol for diabetic foot and venous leg ulcers.","authors":"Windy Cole, Marissa Carter, Caroline Fife, Marissa Docter","doi":"10.25270/wnds/25095","DOIUrl":"10.25270/wnds/25095","url":null,"abstract":"<p><strong>Background: </strong>Traditional randomized controlled trials of efficacy often lack generalizability due to strict inclusion criteria and controlled environments. Real-world evidence trials offer a complementary approach by evaluating the effectiveness of interventions in routine clinical practice.</p><p><strong>Objective: </strong>To prospectively assess the effectiveness of trilayer and single-layer amniotic tissue grafts in treating diabetic foot ulcers and venous leg ulcers using a hybrid platform design compared with historical controls.</p><p><strong>Methods: </strong>This multicenter, umbrella design study includes 2 parallel prospective cohorts with 2 intervention arms each and a shared retrospective standard of care control group. Subjects will be randomized to receive either intervention product 1 or intervention product 2 in addition to standard of care. Retrospective controls will be selected from the US Wound Registry using coarsened exact matching, comparing the primary end point of complete wound closure at 12 weeks and the secondary end point of wound area reduction. Change in quality of life as assessed using a patient-reported outcome measure and pain scores will be evaluated in the subjects in the prospective arm.</p><p><strong>Conclusion: </strong>This protocol outlines a pragmatic, patient-centered approach to evaluating advanced wound care therapies in real-world settings.</p>","PeriodicalId":23752,"journal":{"name":"Wounds : a compendium of clinical research and practice","volume":"37 11","pages":"445-450"},"PeriodicalIF":1.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent Martorell ulcer in a patient with hypertension: a therapeutic success with pentoxifylline.","authors":"Peter A Sorensen, Katherine Palmisano","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Martorell ulcer is a rare skin condition that occurs in individuals with a history of long-standing uncontrolled hypertension. Martorell ulcer is often misdiagnosed on initial evaluation. Treatment primarily consists of tight pharmaceutical control of blood pressure and skin grafting. These treatments have high rates of success and often result in complete healing of the ulcer.</p><p><strong>Case report: </strong>A 68-year-old female with Martorell ulcer on the posterolateral aspect of the left lower limb was unable to undergo either of the aforementioned primary treatments because of a complicated history of cerebral hypoperfusion secondary to multiple strokes that necessitated maintaining her blood pressure at a higher than normal range. After little success with local wound care, the patient was placed on pentoxifylline 400 mg three times a day. Complete healing of the Martorell ulcer was observed, and weaning from pentoxifylline occurred over the course of 28 days. Five months later, the patient presented with recurrence of Martorell ulcer, this time on the contralateral lower limb. Prompt treatment with pentoxifylline was implemented, and the ulcer was completely healed in 29 days.</p><p><strong>Conclusion: </strong>This unique case highlights pentoxifylline as a potentially effective alternative treatment for Martorell ulcer in patients who are unable to undergo first-line treatments. The reproducibility of healing on recurrence in this case further supports consideration of this medication in select patients.</p>","PeriodicalId":23752,"journal":{"name":"Wounds : a compendium of clinical research and practice","volume":"37 10","pages":"393-396"},"PeriodicalIF":1.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topical Products for the Protection of Periwound Skin: A Scoping Review.","authors":"Giovanny Andrés Perez Jaimes, Wilmer Julián Rueda Barrera, Leidy Johanna Rueda Díaz","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>The periwound skin influences the evolution of the wound. Among the mechanisms that affect it are the wound's own exudate and the use of therapeutic support devices.</p><p><strong>Objective: </strong>The objective of this scoping review is to map out topical products that have been implemented and evaluated for either the protection or treatment of injuries caused by exudate or the use of adhesives or therapeutic dressings on the periwound skin of acute or chronic wounds.</p><p><strong>Methods: </strong>The methodology for scoping reviews proposed by the Joanna Briggs Institute was adopted, and a 3-step search strategy was carried out. The first search was limited to MEDLINE and CINAHL. Subsequently, a search was conducted with the identified key words and the terms of the index for the selected databases. Finally, additional studies were sought in the references of all identified publications. Two reviewers conducted the searches independently. Literature in the English, Spanish, and Portuguese languages was included.</p><p><strong>Results: </strong>A total of 1229 studies were identified, 12 of which met the inclusion criteria defined for this review. From the included studies, 12 products were identified for wounds of different etiologies, with the most frequent being the alcohol-free barrier film and zinc oxide.</p><p><strong>Conclusions: </strong>To date, the level of evidence is low. It is necessary to develop more robust research that improves the quality of the literature available for treating people with wounds.</p>","PeriodicalId":23752,"journal":{"name":"Wounds : a compendium of clinical research and practice","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38288368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of Acute and Chronic Wounds Using Negative Pressure Wound Therapy With Instillation and Dwell Time: A Retrospective Review of a 100-Patient Cohort in Padova, Italy.","authors":"Franco Bassetto, Eleonora de Antoni, Sandro Rizzato, Carlotta Scarpa","doi":"10.25270/wnds/081421.01","DOIUrl":"10.25270/wnds/081421.01","url":null,"abstract":"<p><strong>Introduction: </strong>The presence of debris covering a wound surface significantly impedes progression toward closure. Negative pressure wound therapy with instillation and dwell time (NPWTi-d) of topical wound solutions is a versatile tool that can be applied to various wound types to promote wound healing. At the University Hospital of Padova in Padova, Italy, NPWTi-d has been incorporated into wound management plans that include debridement and antibiotic therapy, as necessary, for a diverse population of patients with open wounds, including acute, chronic, and infected wounds.</p><p><strong>Objective: </strong>A retrospective analysis of 100 patients (53 male, 47 female; age range, 22-95 years) who underwent NPWTi-d was performed, and key healing outcomes observed in subgroups differentiated by sex, wound etiology, initial wound size, and topical instillation solution were reported.</p><p><strong>Materials and methods: </strong>Wound types included vascular ulcers, surgical wounds, dehiscences, and trauma; anatomic location of the wounds varied. Negative pressure wound therapy with instillation (0.05% sodium hypochlorite, normal saline, or 0.25% acetic acid) was implemented with a dwell time of 3 minutes to 10 minutes, followed by a negative pressure cycle length of 2 hours to 3.5 hours at -75 mm Hg to -125 mm Hg. Dressings were changed approximately every 3 days.</p><p><strong>Results: </strong>After a median of 11 days (range, 1-35 days), the wound surface area significantly decreased (P <.0001), percentage of infected wounds declined from 72% to 46%, and wound closure was attained in 91% of cases. A significant reduction in wound surface area was detected in both sexes, small- and medium-sized wounds, vascular ulcers, surgical wounds, dehiscences, trauma wounds, and pressure ulcers (P <.05). This effect was detected in wounds regardless of topical instillation solution (P <.0001).</p><p><strong>Conclusions: </strong>This study showed that NPWTi-d is a valuable treatment option in a variety of circumstances and can help the clinician achieve a range of therapy goals based on individual patient needs.</p>","PeriodicalId":23752,"journal":{"name":"Wounds : a compendium of clinical research and practice","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39524229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing chronic wound care with near-infrared spectroscopy imaging: clinical applications, measurement parameters, and insights into healing dynamics.","authors":"Alisha Oropallo, Alex G Ortega-Loayza, Holly Korzendorfer, Francis James, Peggy Dotson, Anna Khimchenko, Vickie R Driver, Sharon Eve Sonenblum","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Chronic wound management is a global health care challenge affecting patient morbidity and quality of life while presenting a substantial economic burden. A critical limitation in effective wound care is the inability to accurately assess microvascular tissue health in real time. This review of near-infrared spectroscopy (NIRS) imaging and its use in wound care emphasizes relevant clinical end points and explores key measurement parameters assessed via NIRS imaging.</p><p><strong>Objective: </strong>To identify, describe, and illustrate NIRS imaging modalities and measurement parameters, and their clinical applications.</p><p><strong>Results: </strong>Clinical studies demonstrated that NIRS imaging can effectively detect poor wound healing early, facilitating timely interventions. Changes in parameters such as oxygenated hemoglobin, deoxygenated hemoglobin, and tissue oxygen saturation have shown strong correlations with wound healing progress, enabling clinicians to make more informed decisions.</p><p><strong>Conclusion: </strong>NIRS imaging advances wound management by providing real-time, noninvasive, and objective data on tissue oxygenation and perfusion. NIRS imaging may objectively complement the standard percentage area reduction assessments during the wound treatment process.</p>","PeriodicalId":23752,"journal":{"name":"Wounds : a compendium of clinical research and practice","volume":"37 10","pages":"384-392"},"PeriodicalIF":1.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of a novel debriding agent based on collagenase and hyaluronate lyase to enhance angiogenesis, stimulate healing, and reduce pain in chronic cutaneous wounds.","authors":"Jorge Adrián Garza-Cerna, Gabriel Ángel Mecott-Rivera, Yanko Castro-Govea, José Juan Pérez-Trujillo, Roberto Montes de Oca-Luna, Daniel Salas-Treviño, Valeria Kopytina, Jorge López Berroa","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Chronic wounds pose a serious health challenge, reducing patient and caregiver quality of life and demanding substantial resources. Debridement is essential for healing, with collagenase being one of the most widely used agents.</p><p><strong>Objective: </strong>To determine the clinical efficacy and safety of a novel bioactive topical formulation combining collagenases G and H, and hyaluronate lyase, for treating chronic ulcers.</p><p><strong>Material and methods: </strong>A prospective 2-arm longitudinal comparative interventional study was conducted. Twenty-five patients were allocated into 2 groups and treated for 21 days with conventional dressing. The intervention group (n = 17) additionally received the novel formulation, whereas the control group (n = 8) did not. Epithelialization, angiogenesis, and wound closure were evaluated, as well as patient satisfaction and product safety in terms of pain and adverse effects.</p><p><strong>Results: </strong>A significantly greater reduction in wound area was observed in the intervention group (baseline median area of 40.0 cm² vs final median area of 16.0 cm²; 60% reduction; P = .0004) compared with controls (baseline median area of 36.0 cm² vs final median area of 24.0 cm²; 33.3% reduction; P = .08). Histological analysis revealed significantly increased angiogenesis in the intervention group (P = .046). The product was rated as highly satisfactory by both physicians and patients in its use and results.</p><p><strong>Conclusion: </strong>The novel formulation demonstrated efficacy in promoting vascularization and reducing the wound area, indicating that it could be a valuable tool for treating chronic ulcers, with significant potential for promoting faster and more effective healing than conventional options.</p>","PeriodicalId":23752,"journal":{"name":"Wounds : a compendium of clinical research and practice","volume":"37 10","pages":"397-408"},"PeriodicalIF":1.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of negative pressure wound therapy with instillation and dwell time on health care utilization and costs in South Africa.","authors":"Maeyane S Moeng, Suleman Vadia, Ashley W Collinsworth, Siobhan Lookess, Paolo Capelli","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Negative pressure wound therapy with instillation and dwell time (NPWTi-d) provides repeated wound cleansing plus the therapeutic benefits of traditional NPWT and has been elevated to a first-line therapy in some regions given evidence of its effectiveness.</p><p><strong>Objective: </strong>To examine the effect of NPWTi-d on health care utilization and costs in South Africa, where NPWTi-d may still be used as a therapy of last resort.</p><p><strong>Methods: </strong>This retrospective study was conducted utilizing a large, South African, private health insurance claims database. A matched cohort of 836 inpatients receiving NPWTi-d or NPWT for various wound types from 2018 through 2022 was created using propensity scoring. Differences in outcomes were compared between groups using t tests.</p><p><strong>Results: </strong>Despite matching, patients who received NPWTi-d were likely more complex than those who received NPWT, as indicated by a longer length of stay (18.5 days and 13.2 days, respectively; P < .001) and higher overall care costs during the index hospital admission. Readmission rates were similar between groups; however, patients who received NPWTi-d were less likely to have visits for wound-related subacute care or rehabilitation (20.1% vs 53.6%). The average cost of this care (in South African rand) was significantly lower for patients receiving NPWTi-d than for those receiving NPWT (R3 231 and R12 317, respectively; P < .001).</p><p><strong>Conclusion: </strong>Although this study had limitations, including a potential selection bias, study data suggest that NPWTi-d may reduce wound-related health care utilization and costs for some patients through decreases in visits for subacute care. More studies are needed to fully assess how NPWTi-d affects wound care pathways, patient outcomes, and costs in South Africa.</p>","PeriodicalId":23752,"journal":{"name":"Wounds : a compendium of clinical research and practice","volume":"37 10","pages":"409-416"},"PeriodicalIF":1.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The use of an acellular wound matrix for Mohs surgical reconstruction: a case series.","authors":"Elizabeth A Ansert, James F Thornton, Amy Du, Alexandra Thornton, Paul J Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Malignancies of the foot are relatively rare and pose a problem for clinicians, with malignant melanoma in this area associated with poor prognosis. The foot has unique anatomy for weight bearing, and preserving this role is imperative; as such, smaller-than-recommended margins are often taken to preserve patient function.</p><p><strong>Objective: </strong>To evaluate the effectiveness of an acellular wound matrix for soft tissue reconstruction after Mohs surgical resection of soft tissue lesions in the foot.</p><p><strong>Materials and methods: </strong>The records of 29 patients who underwent a Mohs surgical procedure from January 2018 to January 2023 were reviewed. The same surgeon performed all these surgeries. The average healing time, wound size, and complication rates were noted.</p><p><strong>Results: </strong>The average patient age was 61.3 years. Twelve of the subjects were male (41.4%) and 17 were female (58.6%). Nineteen (65.5%) of the lesions were diagnosed as melanoma, and 10 lesions (34.5%) were located on the toe. The average wound size after surgical resection was 4.4 cm × 4.0 cm × 0.8 cm. Twenty-two patients healed (75.9%). The average (SD) wound healing time was 139 (90.8) days. Eight patients (27.6%) had postoperative complications.</p><p><strong>Conclusion: </strong>Using an acellular wound matrix after Mohs surgical resection of soft tissue lesions in the foot is a viable option. Patients functioned well after healing. Complication rates are higher in the foot than in other areas of the body using this protocol. Good surgical technique and strong knowledge of the anatomy of the foot and ankle are needed to prevent and manage these complications.</p>","PeriodicalId":23752,"journal":{"name":"Wounds : a compendium of clinical research and practice","volume":"37 10","pages":"378-383"},"PeriodicalIF":1.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The use of near-infrared spectroscopy in assessment of viability and monitoring of healthy trajectories in skin tears.","authors":"Homer-Christian J Reiter, Charles Andersen","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Reliable methods of assessing skin tear flap viability beyond visual inspection would conserve flap tissue and improve outcomes. Near-infrared spectroscopy (NIRS) is a noninvasive, noncontact means of assessing the oxygenation and perfusion status of superficial tissue.</p><p><strong>Objective: </strong>To determine the viable cross-sectional skin flap area in jeopardized skin flaps using NIRS and to determine the average time to heal of conserved skin flaps compared with historical data.</p><p><strong>Methods: </strong>A single-center prospective cohort study was performed at Madigan Army Medical Center between June 2023 and July 2024. Skin flaps were assessed for viability using NIRS. Conservation of skin flaps instead of flap resection leads to a reduction in wound size. Time to heal of the preserved skin flaps was recorded.</p><p><strong>Results: </strong>The median wound cross-sectional area without the preserved skin flap (9.1 cm2 [IQR, 4.2 cm2-11.7 cm2]) was significantly larger than with the preserved skin flap (1.6 cm2 [IQR, 0.9 cm2-2.9 cm2]; P = .0001). The median time to heal with preserved skin flaps was 22 days (IQR, 21 days-41 days) in the present study, compared with 28 days to 42 days in the literature (P = .82).</p><p><strong>Conclusion: </strong>Although this study was underpowered, wound healing times were shorter than historical averages, suggesting that NIRS is a useful tool for assessing tissue viability and conserving skin flaps that have adequate oxygenation.</p>","PeriodicalId":23752,"journal":{"name":"Wounds : a compendium of clinical research and practice","volume":"37 9","pages":"373-377"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145432121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytotherapy for chronic wound management in the era of antibiotic resistance.","authors":"Kajal Rawat, Reema Gabrani","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Chronic wounds, which exhibit prolonged inflammation, impaired healing, and vulnerability to infections, remain a global health challenge, largely driven by the persistence of microbial biofilms and escalating antimicrobial resistance (AMR). Biofilm protects pathogens from the host's immune defenses and conventional antibiotic treatments, sustaining wound chronicity and fostering resistance. Due to the inefficacy of traditional antibiotics in penetrating biofilms and mitigating resistant strains, alternative therapeutic strategies are urgently required.</p><p><strong>Objective: </strong>To review the literature on the use of phytocompounds in chronic wound care.</p><p><strong>Methods: </strong>Various databases such as PubMed, Google Scholar, and Web of Science were thoroughly surveyed by using keywords \"phytocompounds, chronic wounds, wound healing, antimicrobial activity, antibiofilm activity and phytotherapy.\"</p><p><strong>Results: </strong>Findings indicate that the compounds, such as flavonoids, terpenoids, and alkaloids, target various biological pathways, disrupt quorum sensing, and suppress virulence factors, making them valuable for disrupting biofilms and managing AMR. Phytocompounds such as coumarin, tannic acid, resveratrol, and berberine have the potential to enhance wound healing by reducing oxidative stress, promoting clotting, stimulating collagen synthesis, and combating infection. This review highlights complications associated with chronic wounds and explores beneficial phytocompounds for their management.</p><p><strong>Conclusion: </strong>Phytotherapy may play a role in managing wounds by promoting healing, preventing infection, and reducing the need for resistant antibiotics. Combining natural agents with traditional treatments presents a novel and integrative pathway to overcome the limitations posed by antibiotic resistance and biofilm-associated chronicity. While current findings are promising, further validation is needed to fully establish their clinical applications.</p>","PeriodicalId":23752,"journal":{"name":"Wounds : a compendium of clinical research and practice","volume":"37 9","pages":"363-372"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145432143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}