Metabolic dysfunction-associated fatty liver disease in the elderly with diabetic foot ulcers: A longitudinal cohort study.

This study aimed to explore the association between metabolic-associated fatty liver disease (MAFLD) and ulcer recurrence risk in patients with diabetic foot ulcers (DFUs) through an ambispective longitudinal cohort. From December 2013 to December 2022, a total of 482 inpatients with DFUs (PEDIS grade 3 and above with a severe infection) were eligible for inclusion in this study. This was an ambispective longitudinal cohort study. All participants were followed up every 6 months for 9 years with a median of 36 months. According to whether having MAFLD or not, all subjects were placed into two groups: non-MAFLD (n = 351) and MAFLD (n = 131). The association between MAFLD and ulcer recurrence in patients with DFUs was then evaluated through multivariate Cox regression analysis, stratified analyses and Kaplan-Meier survival analysis. Throughout the follow-up period, out of 482 subjects with DFUs, 68 had ulcer recurrence (14.1%). Three Cox regression models were established for data analyses. In the model I (unadjusted), MAFLD was significantly associated with the ulcer recurrence rate in patients with DFUs (HR = 1.79; 95% CI = 1.097-2.92; p = 0.02). Model II (adjusted model I with gender and age) (HR = 1.781; 95% CI = 1.09-2.912; p = 0.021) and model III (adjusted model II with CVD, duration of diabetes and Cr.) (HR = 1.743; 95% CI = 1.065-2.855; p = 0.027) also showed that MAFLD was significantly related to the ulcer recurrence risk in patients with DFUs, respectively. Stratified analysis indicated that subjects aged ≥60 had a greater risk of ulcer recurrence in MAFLD than in non-MAFLD (HR = 2.31; 95% CI = 1.268-4.206; p = 0.006). Kaplan-Meier survival curve analysis showed that ulcer recurrence rate had a significant association with MAFLD (log-rank, p = 0.018). This study indicated a close association between ulcer recurrence risk and MAFLD in patients with DFUs, especially in the elderly (aged ≥60). Therefore, special attention should be paid to the elderly with both DFUs and MAFLD because they have a higher ulcer recurrence rate than other general populations in routine clinical practice.

Endogenous Biological Drivers in Diabetic Lower Limb Wounds Recurrence: Hypothetical Reflections.

An impaired healing response underlies diabetic foot wound chronicity, frequently translating to amputation, disability, and mortality. Diabetics suffer from underappreciated episodes of post-epithelization ulcer recurrence. Recurrence epidemiological data are alarmingly high, so the ulcer is considered in "remission" and not healed from the time it remains epithelialized. Recurrence may result from the combined effects of behavioral and endogenous biological factors. Although the damaging role of behavioral, clinical predisposing factors is undebatable, it still remains elusive in the identification of endogenous biological culprits that may prime the residual scar tissue for recurrence. Furthermore, the event of ulcer recurrence still waits for the identification of a molecular predictor. We propose that ulcer recurrence is deeply impinged by chronic hyperglycemia and its downstream biological effectors, which originate epigenetic drivers that enforce abnormal pathologic phenotypes to dermal fibroblasts and keratinocytes as memory cells. Hyperglycemia-derived cytotoxic reactants accumulate and modify dermal proteins, reduce scar tissue mechanical tolerance, and disrupt fibroblast-secretory activity. Accordingly, the combination of epigenetic and local and systemic cytotoxic signalers induce the onset of "at-risk phenotypes" such as premature skin cell aging, dysmetabolism, inflammatory, pro-degradative, and oxidative programs that may ultimately converge to scar cell demise. Post-epithelialization recurrence rate data are missing in clinical studies of reputed ulcer healing therapies during follow-up periods. Intra-ulcer infiltration of epidermal growth factor exhibits the most consistent remission data with the lowest recurrences during 12-month follow-up. Recurrence data should be regarded as a valuable clinical endpoint during the investigational period for each emergent healing candidate.

Risk factors for foot ulcer recurrence in patients with comorbid diabetic foot osteomyelitis and diabetic nephropathy: A 3-year follow-up study.

This study aimed to explore the risk factors for foot ulcer recurrence in patients with comorbid diabetic foot osteomyelitis (DFO) and diabetic nephropathy (DN). This is a prospective cohort study. Between May 2018 and May 2021, we selected 120 inpatients with comorbid severe diabetic foot infection (PEDIS Grade 3 or above) and DN for inclusion in our study. All cases were followed up for 36 months. The study outcomes were whether foot ulcer recurred and the time to recurrence. The risk factors of ulcer recurrence were analysed by comparing the data of the three groups. According to the recurrence of foot ulcer, the participants were divided into three groups: Group A (no foot ulcer recurrence, n = 89), Group B (foot ulcer recurrence within 12-36 months, n = 19) and Group C (foot ulcer recurrence within 6-12 months, n = 12). The multivariate Cox regression analysis showed that urine albumin-creatinine ratio (UACR) (HR: 1.008, 95% CI: 1.005-1.011, P < .001) and vibration perception threshold (VPT) (HR: 1.064, 95% CI: 1.032-1.096, P < .001) were identified as independent risk factors. Kaplan-Meier curves showed a significant positive association between UACR or VPT and the risk of foot ulcer recurrence (log rank, all P < .05). Areas under the ROC curves for UACR, VPT and the combination of UACR and VPT were 0.802, 0.799 and 0.842, respectively. The best cut-off values of UACR and VPT were 281.51 mg/g and 25.12 V, respectively. In summary, elevated UACR and VPT were independent risk factors. The best clinical cut-off values of UACR and VPT for prediction of foot ulcer recurrence were 281.51 mg/g and 25.12 V, respectively. Besides, our results suggested that microcirculation disorders rather than macrovascular complications play a major role in the recurrence of foot ulcer in patients with comorbid DFO and DN.

Geraniol accelerates the gastric healing, minimizes ulcers recurrence, and reduces anxiolytic-like behavior in ulcerated rodents by oral or inhaled route.

BACKGROUND: Geraniol (GE) is dietary acyclic monoterpene alcohol found in essential oils from aromatic plants with therapeutic value against gastric ulcers already described. HYPOTHESIS/PURPOSE: To assess whether oral GE accelerates gastric healing or prevents ulcer recurrence, and to evaluate the hypothesis that GE promotes antiulcer effects by the inhaled route and that promotes changes in the behavior of ulcerated rodents. METHODS: Gastric healing effects, underlining mechanisms, and behavioral changes were measured in80% acetic acid-induced gastric ulcer model in rats receiving GE by oral (30 mg/kg) or inhaled route (1 mg/L of air/min); whereas the effects of GE to avoid ulcer recurrence was evaluated in mice submitted to 10% acetic acid plus IL-1ß ulcer. RESULTS: GE administered by both routes accelerates gastric healing, increasing mucin and GSH levels, CAT, and GST activities, and reducing MPO activity. Moreover, oral, and inhaled GE minimized ulcer recurrence reducing gastric TNF and IL-6 levels and preserving mucin levels. Interestingly, the inhalation or oral intake of GE promotes anxiolytic-like effects in ulcerated rats. CONCLUSION: Data altogether suggest that the GE accelerates gastric healing through the strengthening of protective factors of the gastric mucosa, promoting a quality healing that reduces the recurrence of the lesion. Besides, the anxiolytic-like effect of GE may also contribute to its gastric healing action since anxiety is recognized as one of the etiologic agents of ulcers.

A multicenter clinical trial evaluating the durability of diabetic foot ulcer healing in ulcers treated with topical oxygen and standard of care versus standard of care alone 1 year post healing.

Multiple clinical trials and real-world studies have demonstrated accelerated healing in diabetic foot ulcers (DFU) treated with advanced modalities, such as topical oxygen therapy (TOT). In addition to healing, the durability of wound closure is a crucial long-term endpoint for DFU clinical trials: an advanced treatment that does not confer a reasonable ulcer-free period will have limited clinical benefit and modest economic value. Preclinical studies suggest that DFUs receiving topical oxygen therapy will experience improved quality of healing: increased collagen deposition and angiogenesis. It is postulated that these changes will translate into a more long-lasting closure for ulcers treated with TOT and SOC compared to ulcers treated with SOC alone. At the conclusion of a recently completed randomised controlled DFU clinical trial evaluating the efficacy of TOT and SOC compared to SOC alone, patients with healed ulcers were asked to enrol in a long-term follow-up study. Healed patients completed four questionnaires through text messages or phone calls within 1-year post completion of the trial. Twenty-nine patients consented to participate in the long-term follow-up trial (17 TOT/SOC and 12 SOC). Only seven subjects were lost to follow up (5 TOT and 2 SOC). This is a surprisingly low number when factoring in the disruption caused by the COVID-19 pandemic that continued throughout the entire follow-up period. In the remaining patients, 85% of the TOT patients and 60% of the SOC remained healed at 1 year. There was one major amputation, which occurred in an SOC-treated patient. The numbers in the long-term follow-up were too small to reach statistical significance; however, there is a strong trend toward more durable closure in ulcers treated with TOT.

Long-term results after internal partial forefoot amputation (resection): a retrospective analysis.

INTRODUCTION: Internal partial forefoot amputation (IPFA) is a treatment option for osteomyelitis and refractory and recurrent chronic ulcers of the forefoot. The aim of our study was to assess the healing rate of chronic ulcers, risk of ulcer recurrence at the same area or re-ulceration at a different area and revision rate in patients treated with IPFA. MATERIALS AND METHODS: All patients who underwent IPFA of a phalanx and/or metatarsal head and/or sesamoids at our institution because of chronic ulceration of the forefoot and/or osteomyelitis from 2004 to 2014 were included. Information about patient characteristics, ulcer healing, new ulcer occurrence, and revision surgery were collected. Kaplan-Meier survival curves were plotted for new ulcer occurrence and revision surgery. RESULTS: A total of 102 patients were included (108 operated feet). 55.6% of our patients had diabetes. In 44 cases, an IPFA of a phalanx was performed, in 60 cases a metatarsal head resection and in 4 cases an isolated resection of sesamoids. The mean follow-up was 40.9 months. 91.2% of ulcers healed after a mean period of 1.3 months. In 56 feet (51.9%), a new ulcer occurred: 11 feet (10.2%) had an ulcer in the same area as initially (= ulcer recurrence), in 45 feet (41.7%) the ulcer was localized elsewhere (= re-ulceration). Revision surgery was necessary in 39 feet (36.1%). Only one major amputation and five complete transmetatarsal forefoot amputations were necessary during the follow-up period. Thus, the major amputation rate was 0.9%, and the minor amputation rate on the same ray was 13.9%. CONCLUSIONS: IPFA is a valuable treatment of chronic ulcers of the forefoot. However, new ulceration is a frequent event following this type of surgery. Our results are consistent with the reported re-ulceration rate after conservative treatment of diabetic foot ulcers. The number of major amputations is low after IPFA. LEVEL OF EVIDENCE: Retrospective Case Series Study (Level IV).

Incidence and Risk Factors Associated With Ulcer Recurrence Among Patients With Diabetic Foot Ulcers Treated in a Multidisciplinary Setting.

BACKGROUND: Recent studies demonstrate favorable diabetic foot ulcer (DFU) healing outcomes with the implementation of a multidisciplinary team. We aimed to describe the incidence of and risk factors associated with ulcer recurrence after initial complete healing among a cohort of patients with DFU treated in a multidisciplinary setting. METHODS: All patients presenting to our multidisciplinary diabetic limb preservation service from 6/2012-04/2018 were enrolled in a prospective database. The incidence of ulcer recurrence after complete wound healing was assessed per limb using the Kaplan-Meier method, and a stepwise multivariable Cox proportional hazards model was created to identify independent predictors of ulcer recurrence. RESULTS: A total of 244 patients with 304 affected limbs were included. Ulcer recurrence rates at one and 3 y after healing were 30.6 ± 3.0% and 64.4 ± 5.2%, respectively. Recurrent ulcers were smaller (4.4 ± 1.1 cm2versus 8.2 ± 1.2 cm2; P = 0.04) and had a lower Wound, Ischemia, and foot Infection stage (stage 4: 7.7% versus 22.4%; P < 0.001) than initial ulcers, and wound healing time was significantly reduced (95.0 ± 9.8 versus 131.8 ± 7.0 d; P = 0.004). Independent predictors of ulcer recurrence included abnormal proprioception (HR, 1.57 [95% CI 1.02-4.43]) and younger age (HR 1.02 per year [95% CI 1.01-1.04]). CONCLUSIONS: In this prospective cohort of patients with DFU, time to diagnosis and healing was significantly lower for recurrent ulcers, and downstaging was common. These data suggest that engaging patients with DFU in a multidisciplinary care model with frequent follow-up and focused patient education may serve to decrease DFU morbidity.

Multidrug resistant organism predicts ulcer recurrence following surgical management of diabetic foot osteomyelitis.

Diabetic foot ulcers commonly precede diabetic foot osteomyelitis (DFO) and once the latter occurs, surgical management is often performed. The presence of osteomyelitis is an independent risk factor for the development of re-ulceration. We investigated the relationship between causative organisms in osteomyelitis and 1-year diabetic foot outcomes (re-ulceration, amputation, and death) following surgical management in an observational cohort of 223 patients. Univariate and multivariate analyses were performed for available demographic, clinical, and laboratory data. In addition, random forest plots were used to identify microbiologic predictors of 1-year outcomes. Patients with osteomyelitis managed surgically were younger and exhibited more painful peripheral neuropathy than outpatients with diabetes alone (both P < .0001). Osteomyelitis proximal margin cultures were diverse, at times polymicrobial, and included multidrug-resistant organisms in 13.9% of the cohort. In patients who underwent surgery, 44.5% experienced a re-ulceration on the same foot within 12 months of surgery. The presence of multidrug-resistant organisms on proximal bone culture was found to be a significant predictor of diabetic foot ulcer recurrence in univariate modelling (P < .001) and importance rankings. This is the first study to use prediction modelling to identify a relationship between multidrug-resistant organisms and diabetic foot ulcer recurrence following DFO.

Editor's Choice - Mid-term Outcomes of Endovenous Laser Ablation in Patients with Active and Healed Venous Ulcers: A Follow-up Study.

OBJECTIVES: The aim of this study was to assess the mid-term ulcer recurrence rate in patients with healed or active venous ulcers treated with endovenous laser ablation (EVLA) for incompetent superficial axial veins and to search for possible risk factors for non-healing and recurrence. METHODS: Consecutive patients treated with EVLA because of a healed or active venous ulcer between 2006 and 2013 were identified in the medical records and quality registry and invited to follow-up, including clinical history, study examination, Duplex ultrasound scanning, ankle brachial pressure, photoplethysmography, venous clinical severity score (VCSS), and health related quality of life (HRQoL) measured with EQ5D. Of 228 patients, 170 (195 legs) fulfilled the inclusion criteria. Twenty patients were interviewed by phone, 27 were unreachable and 11 were excluded. Univariate and multivariate regression analyses were performed to identify possible risk factors for recurrence. RESULTS: The mean follow-up time was 41 months (range 14-89 months). The average age was 66.6 years (range 36-87 years). All 86 legs operated on for an active ulcer had this ulcer healed sometime between the operation and the study examination, but thereafter it recurred in 14 patients (16%). In 109 legs operated on for a healed ulcer, the ulcer recurred in 17 legs (16%). Complications such as permanent sensory loss were seen in 16 legs (8%) and deep venous thrombosis in two legs (1%). Thirty legs (15%) were re-treated for superficial venous incompetence (SVI). Reduced ankle mobility was a risk factor for recurrence in both univariate and multivariate analysis (p=.048). CONCLUSIONS: These midterm results demonstrate that endovenous laser ablation of SVI in patients with healed or active venous ulcers achieves good healing and low ulcer recurrence rates, with a low rate of complications and an acceptable re-intervention rate.

Cost-effectiveness of three adjunct cellular/tissue-derived products used in the management of chronic venous leg ulcers.

OBJECTIVES: Determine the cost-effectiveness of three topically applied cellular/tissue-derived products (CTPs) used as adjunct therapies to standard care in the management of venous leg ulcers (VLUs). METHODS: A three-state Markov model derived from the medical literature was developed to estimate the comparative cost-effectiveness of three CTPs in relation to VLU standard care. CTPs evaluated in the study included extracellular matrix (ECM), human skin equivalent (HSE), and living skin equivalent (LSE). The three Markov states included unhealed, healed, and death. A 1-year time horizon was used to determine the number of ulcer-free weeks and the expected costs of therapies. The payer perspective was taken in the analysis and only the direct costs of care were considered. Sensitivity analyses were performed to gauge model parameter uncertainty. RESULTS: The expected costs for standard care, ECM, HSE, and LSE VLU therapy were $6,132, $6,732, $10,638, and $11,237, while the expected outcomes were 24, 31, 29, and 27 ulcer-free weeks, respectively. ECM was economically dominant among the three CTPs. In the base case of ECM versus standard care, the incremental cost-effectiveness ratio for ECM therapy was $86 per ulcer-free week. Sensitivity analysis did not alter ECM dominance. Clinic visits and home health utilization exhibited the greatest influence on cost. CONCLUSIONS: ECM is the most cost-effective CTP when used in the management of VLUs as an adjunct to standard care. These findings suggest that VLU standard care therapy with ECM can yield potential cost savings and produce better outcomes than do other CTPs.

Prevention of foot ulcers recurrence in patients with diabetes: a systematic review and meta-analysis of randomized controlled trials for the development of the italian guidelines for the treatment of diabetic foot syndrome.

AIM: To compare the effectiveness of preventive interventions in reducing reccurrent diabetic foot ulcers. Meta-analysis (MA) was conducted to address clinical questions on this topic of the Italian guidelines on diabetic foot. METHODS: This MA includes randomized controlled trials evaluating the effectiveness of various preventive interventions, namely: treatment of pre-ulcerative foot lesions, structured educational programs, psychological interventions and the use of therapeutic footwear to relieve plantar pressure in people with diabetes mellitus and a history of previous ulcers. RESULTS: A total of 731 studies were identified and 14 were considered eligible for the analysis. We found that treatments of pre-ulcerative foot lesions did not provide any statistically significant effects (MH-OR: 0.84 [0.31, 2.33], p = 0.74, I2 = 38%). Conversely, structured educational programs were associated with a trend toward reduction of ulcer recurrence risk (MH-OR: 0.13 [0.01, 1.64], p = 0.10, I2 = 88%). No randomized controlled studies assessing the efficacy of psychological interventions have been retrieved. The use of therapeutic footwears can effectively reduce the risk of reulceration in diabetic patients with an history of previous DFU, in particular prefabricated rigid-soled therapeutic footwears showed a significant reduction of the risk of ulcer recurrence in comparison with semirigid soles (MH-OR: 0.17 [0.05, 0.57], p = 0.004). CONCLUSIONS: The study provides low-certainty evidence that, among preventive strategies in patients with previous DFU, rigid-sole therapeutic footwear and structured education programs are capable of reducing the risk of foot re-ulceration.

Plantar pressure measurement in diabetic foot disease: A scoping review.

AIMS/INTRODUCTION: Patients with a healed diabetic foot ulcer (DFU) have a 40% risk of ulcer recurrence within a year. New and effective measures to prevent DFU recurrence are essential. We aimed to highlight emerging trends and future research opportunities in the use of plantar pressure measurement to prevent DFU recurrence. MATERIALS AND METHODS: Our scoping review protocol was drafted using the Preferred Reporting Items for Systematic Reviews and Meta-analysis - Scoping Review protocol. Peer-reviewed, English-language papers were included that addressed both plantar pressure measurement and diabetic foot disease, either as primary studies that have advanced the field or as review papers that provide summaries and/or opinion on the field as a whole, as well as specific papers that provide guidelines for future research and advancement in the field. RESULTS: A total of 24 eligible publications were identified in a literature search using PubMed. A further 36 eligible studies were included after searching the references sections of these publications, leaving a total of 60 publications included in this scoping review. CONCLUSIONS: Plantar pressure measurement can and will play a major role in the prevention of DFU. There is already a strong, albeit limited, evidence base in place to prove its benefit in reducing DFU recurrence. More research is required in larger populations, using remote monitoring in real-world settings, and with improved technology.

Free Flap Limb Salvage and Ulcer Recurrence in Chronic Limb-threatening Ischemia.

Free flap transfer is a well-established treatment for foot reconstruction in patients with chronic limb-threatening ischemia (CLTI) and can achieve prolonged amputation-free survival. However, reports on ulcer recurrence after free flap transfer are scarce, with most focusing on trauma patients. Therefore, we retrospectively reviewed patients with CLTI who underwent free flap reconstruction at our institution over a 17-year period. Patient characteristics, ulcer recurrence rates, activity level, and variables associated with ulcer recurrence were investigated in patients who met the following criteria: successful reconstructive surgery, complete wound healing, and at least 1 year of follow-up. Free flap foot reconstruction was performed in 42 patients (92.9% male, 7.1% female; mean age 57.1 years, range 37-81 years). Among them, 39 patients (92.9%) had diabetes mellitus, 15 (35.7%) had critical limb ischemia, and 15 (35.7%) had end-stage renal disease/hemodialysis. Mean postoperative follow-up was 60.5 (range 12.0-208.0) months. The 5-year primary ulcer recurrence-free survival rate was 48.7%. High activity level and selection of the posterior tibial artery as the recipient artery were significantly associated with ulcer recurrence [hazard ratio, 3.59 and 9.81; P = .046 and P < .001, respectively]. Activity levels were not significantly different before and 1 year after surgery. In conclusion, survival analysis revealed that ulcer recurrence is most likely to occur within the first 2 years after surgery. Although recurrence occurred in approximately half of the patients, most patients maintained activity levels comparable to their preoperative levels.

Cost-effectiveness analysis of intralesional and perilesional recombinant human epidermal growth factor vs hydrocolloid therapy in venous ulcer treatment in the Colombian context.

OBJECTIVE: To perform a comparative analysis of health care expenses and outcomes in response to the question: What is the cost-effectiveness of intralesional and perilesional recombinant human epidermal growth factor (rhEGF) compared with hydrocolloid therapy in patients diagnosed with chronic venous insufficiency without infection in Colombia? METHODS: A Markov model was used to determine cost effectiveness over a 5-year period, considering the perspective of the health system in Colombia. The study included patients aged >18 years diagnosed with chronic venous insufficiency and used clinical studies to calculate the probabilities of epithelialization, infection, recurrence, and mortality. RESULTS: RhEGF is more expensive per unit than hydrocolloids, but it is proven to be effective at healing ulcers in 8 to 12 weeks, even in complex cases. Hydrocolloids, in contrast, typically require 29.5 weeks on average, and ≤46 weeks for complex cases. Despite the cost, rhEGF is more cost effective because it achieves results comparable with hydrocolloid therapy at a lower cost per additional quality-adjusted life-year. CONCLUSIONS: Based on cost-effectiveness analysis, rhEGF is a superior alternative to hydrocolloids for treating venous ulcers in Colombia. Not only is it more affordable, but it also enhances patients' quality of life and streamlines the health care system's resource use.

Risk factors for recurrence of diabetic foot ulcers: prospective follow-up analysis in the Eurodiale subgroup.

Few studies have examined factors associated with diabetic foot ulcer (DFU) recurrence. Using data from patients enrolled in the prospective Eurodiale DFU study, we investigated the frequency of and risk factors for DFU recurrence after healing during a 3-year follow-up period. At our site, 93 Eurodiale-enrolled patients had a healed DFU. Among these, 14 were not alive; of the remaining 79 patients we enrolled 73 in this study. On entry to the Eurodiale study, we assessed demographic factors (age, sex and distance from hospital); diabetes-related factors [duration, and glycated haemoglobin (HbA1c) levels]; comorbidities (obesity, renal failure, smoking and alcohol abuse) and DFU-related factors [peripheral arterial disease, ulcer infection, C-reactive protein (CRP) and; foot deformities]. During the 3-year follow-up period, a DFU had recurred in 42 patients (57.5%). By stepwise logistic regression of findings at initial DFU presentation, the significant independent predictors for recurrence were plantar ulcer location [odds ratio (OR) 8.62, 95% confidence interval (CI) 2.2-33.2]; presence of osteomyelitis (OR 5.17, 95% CI 1.4-18.7); HbA1c > 7.5% ([DCCT], OR 4.07, 95% CI 1.1-15.6) and CRP > 5 mg/l (OR 4.27, 95% CI 1.2-15.7). In these patients with a healed DFU, the majority had a recurrence of DFU during a 3-year follow-up period, despite intensive foot care. The findings at diagnosis of the initial DFU were independent risk factors associated with ulcer recurrence (plantar location, bone infection, poor diabetes control and elevated CRP) and define those at high risk for recurrence, but may be amenable to targeted interventions.

Systematic review and meta-analysis of exercise therapy for venous leg ulcer healing and recurrence.

OBJECTIVE: National guidelines in the United Kingdom have recommended regular exercise for individuals with venous leg ulceration. However, data on the effects of exercise on ulcer healing and recurrence are sparse. In the present study, we aimed to quantify the evidence for exercise regarding venous ulcer healing with respect to the primary outcomes of the proportion of healed ulcers and rate of ulcer recurrence. The secondary outcomes were improvement in ulcer symptoms, ulcer healing time, quality of life, compliance, and adverse events reported. METHODS: The review followed PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines using a registered protocol (CRD42021220925). The MEDLINE and Embase databases and Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, European Union Clinical Trials, and International Standard Randomised Controlled Trial Number registries were searched up to April 6, 2022 and included studies comparing exercise therapy and compression vs compression alone. Data for the proportion of healed ulcers were pooled using a fixed effects meta-analysis. RESULTS: After screening 1046 reports, 7 were included, with 121 participants allocated to exercise therapy and 125 to compression alone. All the reports were of randomized controlled trials and had reported ulcer healing at 12 weeks, with a pooled relative risk of ulcer healing of 1.38 for exercise vs compression (95% confidence interval, 1.11-1.71). Only one study had reported on recurrence; thus, data pooling was not performed. No differences between exercise and usual care were demonstrated. Compliance with exercise ranged from 33% to 81%. The included studies demonstrated low enrollment and a high risk of bias. Also, most of the trials had failed to demonstrate any differences in activity completed between the intervention and control arms. CONCLUSIONS: A paucity of studies has examined leg ulcer recurrence after exercise programs, with no evidence to show that exercise is beneficial. Furthermore, the quality of evidence supporting exercise as an adjunct to ulcer healing is very low, and the trials demonstrated serious methodologic flaws, chiefly in recording the activity undertaken by the participants in the intervention arm. Future randomized controlled trials should implement activity monitoring and standardize the reporting of key patient, ulcer, and reflux characteristics to enable future meaningful meta-analyses to determine the role of exercise as an adjunct to venous leg ulceration healing.

Concurrent laparoscopic highly selective vagotomy with closure of duodenal ulcer perforations show good clinical results as primary repair alone.

OBJECTIVE: To compare clinical and operative results between laparoscopic primary repair (LPR) alone and LPR with highly selective vagotomy (LPR-HSV) in patients with duodenal ulcer perforation. METHODS: Clinical data from patients who underwent either LPR or LPR-HSV by resecting both sides of the neurovascular bundle using an ultrasonic or bipolar electrosurgical device for duodenal ulcer perforations, between 2010 and 2020, were retrospectively collected. Between-group differences in continuous and categorical variables were statistically analysed. RESULTS: Data from 184 patients (mean age, 49.6 years), who underwent either LPR (n = 132) or LPR-HSV (n = 52) were included. The mean operation time was significantly longer in the LPR-HSV group (116.5 ± 39.8 min) than in the LPR group (91.2 ± 33.3 min). Hospital stay was significantly shorter in the LPR-HSV group (8.6 ± 2.6 days) versus the LPR group (11.3 ± 7.1 days). The mean postoperative day of starting soft fluid diet was also significantly shorter in the LPR-HSV group (4.5 ± 1.4 days) than in the LPR group (5.6 ± 4 days). No between-group difference in morbidity rate was observed. The learning curve of the HSV procedure showed a stable procedure time after 10 operations. CONCLUSIONS: LPR with HSV may be a safe and feasible procedure for selective cases who are at high risk for ulcer recurrence.

Risk Factors for Ulcer Recurrence in Diabetic Patients Managed by an Integrated Foot Care Protocol.

The aim of our study was to identify risk factors for the recurrence of diabetic foot ulcers (DFUs) in a selected population of patients in secondary prevention treated, according to International Guidelines, with an integrated foot care protocol by a referral diabetic foot clinic. A retrospective study was performed with the inclusion of selected outpatients with diabetes at higher risk for ulceration with a history of previous ulcer and/or amputation followed in our diabetic foot clinic between January 2015 and December 2021. According to the presence or absence of recurrence, patients were divided into 2 groups: ulcer recurrence and without ulcer recurrence. One hundred twenty-seven (127) patients were included, 47 patients (37%) developed an ulcer recurrence while 80 patients (63%) did not. The mean age was 71.7 years; 65% were male; 97% were affected by type 2 diabetes with a mean duration of 21.1 years, the mean HbA1c was 63 + 21 mmol/mol. Both groups of patients had foot deformities, such as claw and hammertoes; hallux valgus, and prominent metatarsal heads (MTHs). The presence of deformity was significantly associated with ulceration. The group with ulcer recurrence showed a higher rate of prominence MTHs in comparison to a group without ulcer recurrence. The MTHs resulted as the only independent predictor for recurrence. This study shows that the presence of the prominent MTH is a significant risk factor for ulcer recurrence in a selected population of diabetic foot patients treated in the best way with integrated foot care.

Health-related quality of life and associated factors in people with diabetes at high risk of foot ulceration.

BACKGROUND: The health-related quality of life (HRQoL) of people with diabetes-related foot complications has been increasingly reported, mostly from studies of people with a foot ulcer. The aim of this study was to assess HRQoL and determine factors associated with HRQoL in people with diabetes at high risk of foot ulceration. METHODS: In all, 304 participants enrolled in the Diabetic Foot Temperature Trial (DIATEMP) were included in the cross-sectional analysis. HRQoL was measured by the RAND® 36-Item Short Form Health Survey (SF-36) at baseline. Potential factors associated with HRQoL were analysed using multiple linear regression analyses for the eight domains of the SF-36. RESULTS: Participants were predominantly male (72%), mean age 64.6 (±10.5) years, 77% type 2 diabetes and mean duration of diabetes 20 (±14) years. Mean SF-36 domain scores for the General Health (49.2 ± 20.1), Role Physical (50.9 ± 44.7), Physical Function (58.5 ± 27.9) and Vitality domains (59.8 ± 21.6) were lower compared to the Mental Health (78.4 ± 18.0), Social Functioning (75.3 ± 24.2), Role Emotional (73.5 ± 38.9) and Bodily Pain (67.0 ± 27.0) domains. HRQoL was lower than Dutch population-based and general diabetes samples, but higher than in samples with an ulcer. Use of a walking aid was associated with lower HRQoL across all 8 SF-36 domains (ß range - 0.20 to - 0.50), non-Caucasian descent was associated with lower HRQoL in 5 domains (ß range - 0.13 to - 0.17). Not working, higher BMI and younger age were associated with lower HRQoL in 3 domains. CONCLUSIONS: People at high risk of diabetes-related foot ulceration have reduced HRQoL that varies across domains, with the physical domains most affected. Assessing mobility, ethnicity, BMI and job status may be useful in daily practice to screen for people who might benefit from interventions targeting HRQoL. TRIAL REGISTRATION: Netherlands Trial Registration: NTR5403. Registered on 8 September 2015.

Effects of wear and tear of therapeutic footwear in patients remission. A 5-year follow-up study.

AIMS: To assesses the relationship between the wear and tear of therapeutic footwear (TF) and the risk of recurrence in diabetes remission patients. METHODS: Remission patients (N = 115) participated in this 5-year prospective study in a specialized Diabetic Foot Unit between October 2016 and January 2022. Patients' TF was assessed in a three-month interval from Day 0 until ulcer recurrence was found. Primary outcome measure was based on the recurrent event in the forefoot. RESULTS: A total of 82 patients (71.3%) renewed their TF, and 33 patients (28.7%) did not renew their TF during the follow-up period. Patients who failed to renew their TF group experienced more recurrent events (22 vs 14, p <.001, CI [0.04-0.259]) and minor amputations (11 vs 8, p =.002, CI [0.07-0.6]). Both groups showed different recurrence-free survival median times of 205.5 [Interquartile range (IQR) - 188-222] weeks and 89.9 [IQR - 53-126] weeks. Patients who did not renew their TF increased their risk of suffering from a recurrent event in the Cox regression model (p <.001, CI [0.03-0.38], Hazzard Ratio 0.147). CONCLUSIONS: Patients who renewed their TF because of wear and tear experienced lower recurrences and minor amputations.