Ulcer Depth Research Articles

Topical chlorhexidine 0.2% versus topical natamycin 5% for fungal keratitis in Nepal: rationale and design of a randomised controlled non-inferiority trial.

IntroductionFungal infections of the cornea, fungal keratitis (FK), are challenging to treat. Current topical antifungals are not always effective and are often unavailable, particularly in low-income and middle-income countries where most cases occur. Topical natamycin 5% is usually first-line treatment, however, even when treated intensively, infections may progress to perforation of the eye in around a quarter of cases. Alternative antifungal medications are needed to treat this blinding disease.Chlorhexidine is an antiseptic agent with antibacterial and antifungal properties. Previous pilot studies suggest that topical chlorhexidine 0.2% compares favourably with topical natamycin. Full-scale randomised controlled trials (RCTs) of topical chlorhexidine 0.2% are warranted to answer this question definitively.Methods and analysisWe will test the hypothesis that topical chlorhexidine 0.2% is non-inferior to topical natamycin 5% in a two-arm, single-masked RCT. Participants are adults with FK presenting to a tertiary ophthalmic hospital in Nepal. Baseline assessment includes history, examination, photography, in vivo confocal microscopy and cornea scrapes for microbiology. Participants will be randomised to alternative topical antifungal treatments (topical chlorhexidine 0.2% and topical natamycin 5%; 1:1 ratio, 2–6 random block size). Patients are reviewed at day 2, day 7 (with reculture), day 14, day 21, month 2 and month 3. The primary outcome is the best spectacle corrected visual acuity (BSCVA) at 3 months. Primary analysis (intention to treat) will be by linear regression, with treatment arm and baseline BSCVA prespecified covariates. Secondary outcomes include epithelial healing time, scar/infiltrate size, ulcer depth, hypopyon size, perforation and/or therapeutic penetrating keratoplasty (corneal transplant), positive reculture rate (day 7) and quality of life (EuroQol-5 dimensions, WHO/PBD-VF20, WHOQOL-BREF).Ethics and disseminationThe Nepal Health Research Council, the Nepal Department of Drug Administration and the London School of Hygiene and Tropical Medicine ethics committee have approved the trial. The results will be presented at local and international meetings and submitted to peer-reviewed journals for publication.Trial registration numberISRCTN14332621; pre-results.

Comorbidities associated with non- healing of plantar ulcers in leprosy patients.

BackgroundNon-healing plantar ulcers are one of the significant causes of disability in leprosy patients. Plantar ulcers often take months or years to heal, affecting the patient’s quality of life. Presence of comorbid conditions in these patients can delay wound healing. The study aimed to evaluate the role of associated comorbid conditions as risk factors in ulcer healing.Methodology/Principal findingsA total of 66 leprosy patients with plantar ulcers registered at LEPRA Society-Blue Peter Public Health and Research Center (BPHRC), Hyderabad, India from June 2018 to June 2019 were studied. Comprehensive clinical assessment was done, including screening for comorbid conditions and treated as per the recommended guidelines. About two-thirds of the participants were aged 50 and above, of which more than half were illiterates, and 93.5% were living below the poverty line. Majority of ulcers were seen on the forefoot; with the head of meta-tarsal bone 27 (41.6%) as the commonest site, followed by calcaneum 23 (38.3%) and great toe 10 (16.6%). Mean ulcer depth was 0.61 (0.57) cm, the area was 5.24 (6.73) cm2 and ulcer volume was 4.72 (14.33) cm3. Ulcer dimensions were significantly associated with low body mass index, hypertension and smoking.Conclusions/SignificanceIdentifying the risk factors delaying wound healing and detailed assessment of ulcers are of profound importance to predict the outcome of plantar ulcers in leprosy patients. The study findings indicate the need for better policies by the leprosy control program for the comprehensive management of plantar ulcers.

MRI and Clinical Risk Indicators for Osteomyelitis.

Introduction. The sensitivity and specificity for magnetic resonance imaging (MRI) diagnosis of osteomyelitis is 90% and 80%, respectively; findings include bone marrow edema, T2-weighted image hyperintensity (HI-T2WI), T1-weighted image confluent signal(CS-T1WI), and cortical erosion (CE). The goal is to determine which risk factors and MRI findings are most predictive of osteomyelitis. Materials and Methods. After institutional review board approval, records of patients who underwent bone biopsy of the foot/ankle between 2015 and 2017 were reviewed. Diagnosis was determined histologically. Blinded MRI review identified indicators of osteomyelitis: HI-T2WI, CS-T1WI, ulcer depth, and CE. Bivariate and multivariate regression determined an association between osteomyelitis and radiographic indicators. Results. Of 59 subjects, 41 (69.5%) and 18 (30.5%) had pathologic evidence of osteomyelitis or were indeterminate. The sensitivity and specificity by radiologist diagnosis was 51.4% and 91.7%, respectively. Diabetes (relative risk [RR]=2.9, 95% CI = 1.0.8-7.77, P = .034), CS-T1WI (RR = 1.6, 95% CI = 1.23-2.20, P < .001), and CE (RR = 1.8, 95% CI = 1.34-2.28, P < .001) were risk factors on bivariate analysis. Ulcer depth demonstrated a trend toward statistical significance. Diabetes (RR = 2.4, 95% CI = 1.00-5.69, P = .049) and CE (RR = 1.7, 95% CI = 1.27-2.37, P < .001) were independent risk factors on multivariate analysis. Discussion. Diabetes and CS-T1WI are independent risk factors for pedal osteomyelitis. Patients with diabetes, CS-T1WI, and CE should be evaluated for osteomyelitis with recommendation for bone biopsy in appropriate clinical settings.Levels of Evidence: Level III Retrospective Comparative Study.

PDB111 A COMPARATIVE EFFECTIVENESS RESEARCH STUDY OF A NATIVE TYPE I COLLAGEN MATRIX PLUS POLYHEXAMETHYLENE BIGUANIDE ANTIMICROBIAL AND A CRYOPRESERVED CADAVERIC SKIN ALLOGRAFT FOR USE IN DIABETIC FOOT ULCERS - A NON-INFERIORITY ANALYSIS

Real-world effectiveness was evaluated in a large patient population at 189 US treatment facilities comparing a purified native cross-linked extracellular matrix plus polyhexamethylene biguanide antimicrobial barrier (PCMP) and a cryopreserved cadaveric skin allograft (CCSA) for use in diabetic foot ulcers (DFUs). Electronic medical records were the source of these retrospective data. Treatment records collected from 2011-2019 on 945 patients (1,032 DFUs) were analyzed. Exclusion criteria were lack of baseline wound measurements or follow-up visits. Evaluations were performed on 314 PCMP patients (349 DFUs), and 631 CCSA patients (683 DFUs). Treatment cohorts were well matched. Baseline, mean areas were 6.2 and 7.8 cm2, mean depths were 4.0 and 3.5 mm, and median durations were 9.3 and 7.0 months, for PCMP and CCSA respectively. The median number of treatment applications was 2.0 in both groups, and the mean interval between treatment applications was 14.4 vs 24.1 days for PCMP and CCSA respectively. A Cox proportional hazards regression analysis (Cox) that adjusted for ulcer size, depth, and duration was used to compute frequency and probability of wound closure. The PCMP vs CCSA frequencies of wound closure were comparable at all study timepoints including week 4 (11 vs 10%), 8 (25 vs 24%), and 12 (36 vs 37%) respectively (p=0.20). PCMP demonstrated a comparable probability of wound healing vs CCSA treatment (Hazard Ratio=0.89 [95% CI: 0.75, 1.06]; p=0.20). In a Non-Inferiority (NI) analysis, PCMB demonstrated equivalence to CCSA when tested at a clinical margin of 20% (p=0.03). These real-world data demonstrate that PCMP vs CCSA showed comparable wound closure outcomes when used in DFUs. The NI design allows a valid conclusion of statistically significant equivalence between PCMP and CCSA at the clinical margin tested. These findings may inform wound care treatment algorithms and have meaningful clinical and health care economic implications.

PIT14 COMPARATIVE EFFECTIVENESS OF A BILAYERED LIVING CELLULAR CONSTRUCT AND A DEHYDRATED HUMAN AMNION/CHORION MEMBRANE FOR THE TREATMENT OF PRESSURE ULCERS

Using deidentified, patient data from a wound-specific electronic medical record (WoundExpert, Net Health, PA, US), we compared the effectiveness of a bilayered living cellular construct (BLCC) to a dehydrated human amnion/chorion membrane (dHACM) for the treatment of pressure ulcers (PRUs) in a retrospective comparative effectiveness (CER) study. PRUs over anatomical locations including sacrum, coccyx, greater trochanter, ischial tuberosity, calcaneus, and lateral malleolus were included. Data from 1,189 refractory PRUs, Stages II–IV, with surface areas between 1 and 200 cm2 in size, treated between July 2014 and October 2019 at 188 wound care facilities across the US were analyzed. All treated PRUs that closed by <40% within 28 days of the first treatment application were included. Unadjusted time to event analyses were performed by the method of Kaplan-Meier (K-M), and adjusted analyses were performed using Cox’s proportional hazards regression (Cox). Patient baseline demographics and wound characteristics were comparable between groups. Cox derived estimates of wound closure for BLCC (728 wounds) were significantly greater (p=0.0001; Wald Test) by weeks 12 (36% vs. 27%), 18 (51% vs. 39%), and 24 (59% vs. 47%) respectively, compared with dHACM (461 wounds). BLCC treatment significantly reduced the median time to wound closure by 21%, achieving healing 4.4 weeks sooner (17.0 vs. 21.4 weeks, p=0.0001; Wald Test). Cox regression analysis adjusting for multiple covariates including ulcer area, depth, and duration showed that treatment with BLCC increased the probability of healing by 38% compared with dHACM (Hazard Ratio=1.38 [95% confidence interval (1.17, 1.62)], p=0.0001). These real-world data demonstrate that BLCC significantly improved wound closure compared to dHACM for the treatment of PRUs. The improvements in the probability, speed and the incidence of wound closure in VLUs treated with BLCC suggest a greater clinical benefit as well as a potential cost savings benefit.

Design of a potentially registrational study of sakigake-designated GCSF-Mobilized autologous CD34 cell (CLBS12) Therapy of no-option critical limb ischemia including arteriosclerosis obliterans and Buerger's Disease

Background & Aim CLBS12 (autologous, mobilized peripheral blood derived selected CD34 cells) has previously been studied for the treatment of No-Option Critical Limb Ischemia (NOCLI) in Phase 1 and 2 studies in Japan and the United States. These studies demonstrated statistically significant improvement in key outcome measures including reduced Rutherford category, improved walking distance, reduction in pain, improvement in blood flow and tissue oxygenation, reduction in size and number of ulcers, and improved amputation-free survival. In one of the Japan studies, more than 80% of subjects treated with a single administration of CD34 cells became CLI-free and maintained this status through 4 years of observation. The promising results of these studies led to discussions with the PMDA regarding the design of a confirmatory study that, with a favorable outcome, could support registration of CLBS12 in Japan for NOCLI under the new regenerative medicine regulations. Methods, Results & Conclusion The study is a prospective, randomized clinical trial in subjects with arteriosclerosis obliterans (ASO; n=30) or Buerger's Disease (BD; n=5). All patients receive standard-of-care treatment (SOC). The study calls for randomization of 30 subjects with ASO to receive either CLBS12 or to continue with SOC alone. Additionally, 5 subjects with BD were to be allocated to a sub-study and receive CLBS12 while continuing SOC treatment. The primary endpoint for the study is ability to achieve a continuous CLI-free state. Other key measures include progression-free, amputation-free, and overall survival; Rutherford category; tissue oxygenation; blood flow; ulcer size, depth, and infection; pain; and quality-of-life. For preparation of CLBS12, subjects are mobilized with GCSF 5 µg/day for 5 days, then undergo apheresis to collect a mononuclear cell fraction. CD34 cells are separated using a magnetic separation method. CLBS12 is formulated as a cell suspension in proprietary media in a 10 mL volume for administration as a series of 20 intramuscular injections in one affected limb. The study was initiated in December 2017 and is expected to be completed in 2020. The BD sub-study has enrolled 6 subjects and half have achieved a continuous CLI-free state. Interim data from the trial will be presented.

Ileal and Rectal Ulcer Size Affects the Ability to Achieve Endoscopic Remission: A Post hoc Analysis of the SONIC Trial.

It is unclear how baseline endoscopic characteristics in Crohn's disease (CD) affect the ability to achieve endoscopic remission (ER). We aimed to determine the endoscopic prognostic factors that influence achieving ER in CD. This post hoc analysis of SONIC (NCT00094458; YODA #2019-3980) evaluated baseline and week 26 endoscopy indices in 172 patients using the CD Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score for CD. The impact of baseline ulcer depth and size on achieving week 26 ER was assessed using multivariate logistic regression models adjusted for confounders. The ER rate of ileal ulcers was significantly lower than ER rates throughout the colon (P < 0.0001). Ileal ulcers >2 cm were less likely to achieve ER compared with smaller ulcers {odds ratio (OR) 0.31 (95% confidence interval [CI] 0.11-0.89), P = 0.03}. Similarly, rectal ulcers >2 cm were associated with reduced odds of week 26 ER (OR 0.26 [95% CI 0.08-0.80], P = 0.02). Ulcer size in other colonic segments did not affect the achievement of week 26 ER. Deep ileal and rectal ulcers >2 cm compared with smaller or superficial ulcers were even less likely to achieve week 26 ER (ileum: OR 0.10, 95% CI 0.02-0.68, P = 0.02; rectum: OR 0.12, 0.02-0.82, P = 0.03). High baseline Simple Endoscopic Score for CD (≥16) or CDEIS scores (≥12) did not affect achieving week 26 ER. Patients with larger and deep ulcers in the ileum or rectum may have difficulty achieving ER. Overall degree of endoscopic inflammation as measured numerically by endoscopic scores does not affect the likelihood of achieving week 26 ER.

Natural History, Clinical Significance, and the Role of Vascular Referral in the Management of Penetrating Ulcers of the Abdominal Aorta

Penetrating ulcers of the abdominal aorta (PUAA) are an increasingly common finding on abdominal imaging studies; however, their significance and natural history are not well described. This study's objective was to analyze the demographics, presentation, and outcomes of patients with a radiographic diagnosis of PUAA. Patients at our tertiary referral center were identified for inclusion based on a search for the term "penetrating ulcer" in abdominal computed tomography and magnetic resonance imaging reports between January 2014 and December 2017. Patients' electronic medical records were retrospectively reviewed to determine baseline medical characteristics, imaging indication, and subsequent clinical course, interventions, and outcomes. Aortic diameters and ulcer depths were measured by a single observer on initial and follow-up imaging to assess for association with concomitant aortic pathology, evolving aortic disease, and ulcer progression, defined as increase in depth of ≥ 1mm. Statistical analysis was performed using STATA 16 (College Station, TX: StataCorp LLC), and a threshold P-value of <0.05 was set for significance. Ninety-two patients with PUAA were identified; 57 (62%) were male. The mean age at diagnosis was 79.3years, and comorbidities included hypertension (74%), hyperlipidemia (65%), and malignancy (34%). The most common indication for imaging was chest, back, or abdominal pain (19%). On initial imaging, the mean ulcer depth was 1cm (range from 0.2cm to 3.4cm). Concomitant abdominal aortic dilation ≥ 3cm was found in 34 (37%) patients. Thirty-six (39%) patients had a vascular surgery consultation immediately after radiographic diagnosis. Follow-up axial imaging was performed on 27 (29%) untreated patients. The overall sample's mean ulcer depth remained essentially unchanged from initial measurement (P=0.99); however, 14 (52%) patients with follow-up imaging were found to have increased overall aortic diameter. Of the total 92 patients, 9 (10%) underwent an endovascular abdominal aortic intervention during the review period: 2 for symptomatic PUAA and the remainder for progression of concomitant aneurysmal disease. All-cause mortality was 5% during the mean follow-up period of 21.9months (range 0 to 72.5months). Of the patients lost to follow-up, 61% did not receive vascular referral after initial diagnosis. PUAA are typically incidental findings identified in elderly, comorbid patients undergoing imaging for an unrelated indication. Although isolated findings of asymptomatic PUAA rarely require surgical intervention, these patients we argue would benefit from vascular surgery referral for long-term follow-up and interval imaging to assess for disease progression and concomitant aortic degeneration, which may necessitate repair. In addition, we observed that most of those patients lost to follow-up did not receive vascular consultation, suggesting that lack of involvement of vascular specialists at the time of diagnosis is a missed opportunity to secure appropriate follow-up and management.

Predicting osteomyelitis in patients whose initial MRI demonstrated bone marrow edema without corresponding T1 signal marrow replacement.

We endeavored to determine which characteristics of diabetic ulcers portend the strongest risk for osteomyelitis in patients whose initial T1-weighted imaging was normal. By determining which features have a greater risk for osteomyelitis, clinicians can treat patients more aggressively to reduce the sequela of inadequately treated osteomyelitis. We performed a retrospective analysis of MR imaging from 60 pedal ulcers with suspected osteomyelitis. Ulcer dimensions and depth were measured. Ratios of marrow ROI/joint fluid ROI on T2/STIR sequences were obtained. Progression to osteomyelitis on subsequent MRI was characterized by loss of normal marrow signal on T1-weighted images. Statistical analysis was performed with a two-sample t test and Cox proportional hazard model. A p value < 0.05 was used as the threshold for statistical significance. Sixty MR exams were identified. Thirty-four progressed to osteomyelitis. Marrow ROI/joint fluid ratios averaged 65% in the osteomyelitis group, and 45% in the non-osteomyelitis group, p < 0.001. ROI ratios > 53% had a 6.5-fold increased risk of osteomyelitis, p < 0.001. Proximity to bone averaged 6mm in the osteomyelitis group and 9mm in the non-osteomyelitis group, p = 0.02. Ulcer size averaged 4cm2 in the osteomyelitis group versus 2.4cm2 in the non-osteomyelitis group, p = 0.07. Ulcers greater than 3cm2 has a 2-fold increase in the risk of osteomyelitis, p = 0.04. Increasing bone marrow ROI signal/joint fluid ratios on T2/STIR images were the strongest risk factors for developing osteomyelitis, while ulcer size and depth are weaker predictors.

Comparative study between Negative Pressure Wound Therapy (NPWT) and Standard Moist Wound Dressing (SMWD) in management of diabetic non ischemic foot ulcers

Abstract Background and Aims Diabetes is rapidly increasing in prevalence worldwide and surgery in patients with diabetic foot is becoming more common. Foot complications are a major cause of admissions in diabetic patients, and comprise a disproportionately high number of hospital days because of multiple surgical procedures and prolonged length of stay in hospital. Diabetic foot is an umbrella term for foot problems in patients with diabetes mellitus. Foot disorders such as ulceration, infection and gangrene are the most common, complex and costly sequelae of diabetes mellitus. The optimal therapy for diabetic foot ulcers remains ill-defined. Saline-moistened gauze has been the standard method; however, it has been difficult to continuously maintain a moist wound environment with these dressings. This has led to the development of various hydrocolloid wound gels, which provided more consistent moisture retention. Refinements in topical ointments have resulted in the addition of various pharmacological agents including growth factors and enzymatic debridement compounds. Hyperbaric oxygen therapy and culture skin substitutes are other wound therapies that have been advocated. All these therapies are associated with significant expense and are being utilized in some situations without sufficient scientific evidence demonstrating their efficacy. Therefore, the search for an efficacious, convenient and cost-effective therapy continues. Negative Pressure Wound Therapy (NPWT) is a newer noninvasive adjunctive therapy system that uses controlled negative pressure using Vacuum-Assisted Closure device (VAC) to help promote wound healing by removing fluid from open wounds through a sealed dressing and tubing which is connected to a collection container. The use of sub-atmospheric pressure dressings, available commercially as a VAC device, has been shown to be an effective way to accelerate healing of various wounds. This was aimed to compare wound outcome, limb salvage, and cost effectiveness between Negative pressure wound therapy (NPWT) and Standard moist wound therapy (SMWT) in management of diabetic non ischemic foot ulcers. Methods we performed a cohort study involving 30 patients with active diabetic foot ulcers, in a high volume tertiary referral vascular center. They were divided into 2 groups: 15 patients (group A) were prescribed NPWT and the other 15 patients (group B) received SMWD. During follow up visits, progress of healing was evaluated and documented in the form of change in wound diameter, depth, up or down scaling along UTWC, wound status at 2, 4, 8, and 12 weeks and 4 weekly thereafter till complete epithelialization. Results As regard to ulcer depth there were statistically significant difference between the 2 groups during follow up duration of the study after 4 weeks with group A showing faster decrease in ulcer depth than group B denoting faster formation of granulation tissue. As regard to complete granulation of ulcer there were statistically significant difference between the 2 groups during follow up duration of the study markedly shown after 6 weeks with group A showing complete ulcer granulation faster than group B, with statistically significant difference as regard to number of days on dressing and follow up duration in weeks between the 2 groups with group A showing lesser number of days on dressing and shorter follow up duration in weeks than group B. Conclusion NPWT has a definitive role in promotion of proliferation of granulation tissue, reduction in the wound size, by and rapid clearing of bacterial load. Our data demonstrates that negative pressure wound dressings decrease the wound size more effectively than saline gauze dressings over the first 4 weeks of therapy. It is suggested that NPWT is a cost-effective, easy to use and patient-friendly method of treating diabetic foot ulcers which helps in early closure of wounds, preventing complications and hence promising a better outcome.

Light and Electron Microscopic Studies on the Possible Protective Effect of Ginger on the Gastric Fundic Mucosa of Adult Male Albino Rats Treated with 5- Fluorouracil

Introduction: 5-fluorouracil is a potent antimetabolite chemotherapeutic medication used for treatment of various malignancies . Using this agent result in toxic effect mainly in the lining of digestive tract. To ameliorate 5 FU toxic effect ginger was implicated in this study.Aim of the Work: To evaluate the microscopic effect of 5-fluorouracil on gastric fundus mucosa in rat models . and to study the possible beneficial role of ginger in the ameliorations of these changes. Material and Methods: Forty-eight adult male albino rates were divided into four groups: group I (control), group II received ginger orally in a dose of 200 mg/kg/day , group III received 5-fluorouracil (15 mg/kg) intraperitoneally and group IV received 5 FU and Ginger as previous doses for 5 days. The fundic part of stomach was excised and subjected to light and electron microscopic studies.Results: In 5 FU treated group, the fundic gastric mucosa showed multiple areas of tissue loss , congested dilated blood vessels and extravasated red blood cells and mononuclear infiltration were seen between fundic gland cells. Parietal cells showed ballooned appearance, vacuolated cytoplasm, and pykontic nuclei. PAS/ Alcian blue stained sections showed marked reduction in both alcian blue and PAS positive reaction. There was strong positive cytoplasmic reaction in the apical and middle parts of the fundic glands for caspase 3 while large number of parietal cells were stained positive for Cox 2. These histological findings were improved after ginger administration. Histomorphometric study revealed significant weight reduction, increased mucosal ulcer depth, decreased mucosal thickness and increased number of parietal cells in 5 FU treated group when compared to control group. Conclusion: 5FU causes gastric damage in rat model. Ginger supplementation could be used to alleviate the damaging pathological effect on gastric fundus.

Opposite Roles of BAP1 in Overall Survival of Uveal Melanoma and Cutaneous Melanoma.

Background: BRCA1-Associated Protein 1 (BAP1) germline mutations predispose individuals to cancers, including uveal melanoma (UM) and cutaneous melanoma (CM). BAP1 loss is common in UM and is associated with a worse prognosis. BAP1 loss is rare in CM and the outcome is unclear. Methods: UM and CM data was retrieved from The Cancer Genome Atlas (TCGA) database. Cox regression model was performed to examine whether BAP1 mRNA levels or copy number variations were associated with overall survival (OS). Results: BAP1-low mRNA predicted a poor OS in UM (HR = 9.57, 95% CI: 2.82, 32.5) but a contrasting better OS in CM (HR = 0.73, 95% CI: 0.56, 0.95). These results remained unchanged after adjusting for sex, age, and stage in UM and CM, or after adjusting for ulceration or Breslow depth in CM. Additionally, low BAP1 mRNA predicted a better OS in CM patients older than 50 years but not in younger patients. Co-expression and enrichment analysis revealed differential genes and mutations that were correlated with BAP1 expression levels in UM and CM tumors. Conclusions: Low BAP1 mRNA was significantly associated with a better OS in CM patients, in sharp contrast to UM. High BAP1 expression in CM was significantly associated with over-expressed CDK1, BCL2, and KIT at the protein level which may explain the poor OS in this sub-group of patients. Function of BAP1 was largely different in CM and UM despite of a small subset of shared co-expressed genes.

P546 Ileal ulcer size significantly impacts the ability to achieve endoscopic remission: a post-hoc analysis from the SONIC trial

Abstract Background Endoscopic remission (ER) is an important target of treatment for Crohn’s disease (CD). However, it is unclear how individual baseline endoscopic characteristics impact the ability to achieve ER. We aimed to determine endoscopic prognostic factors that influence the likelihood of achieving ER in CD. Methods This was a post-hoc analysis of SONIC (NCT00094458; YODA #2019–3980), where data from 172 patients who had endoscopic scores at baseline and at week 26 were evaluated. Individual components of the Crohn’s Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score for Crohn’s disease (SES-CD) indices were used to evaluate the impact of baseline ulcer depth (CDEIS) and size (SES-CD) on likelihood of achieving ER at week 26. Ileum and colon segments were evaluated separately. Multivariate logistic regression models were used to evaluate the relationship between baseline endoscopic findings and achievement of ER in each segment at week 26, after accounting for known confounders including disease duration and treatment allocation. Results are presented as odds ratios (OR) with 95% confidence intervals (CI). Results The rate of ulcer improvement in the ileum was significantly lower than rates of healing throughout the colon (p &amp;lt; 0.0001) (see figure). Patients with ulcer size &amp;gt;2 cm in the ileum were less likely to achieve ER of the ileum compared with patients with ulcer size &amp;lt;2 cm (OR 0.31, 95% CI 0.11–0.89, p = 0.03). Ulcer size did not consistently impact likelihood of achieving week 26 ER in colonic segments. Patients with ileal ulcer size &amp;gt; 2 cm that were also deep were less likely to achieve ileal ER, when compared with patients with smaller or superficial ulcers (OR 0.10, 95% CI 0.02–0.68, p = 0.02). High baseline SES-CD score (&amp;gt;16) or CDEIS score (&amp;gt;12) did not impact the likelihood of achieving week 26 ER. Conclusion Ulcer size and depth, but not the overall degree of endoscopic inflammation, seem to impact likelihood of achieving week 26 ER. ER may be more difficult to achieve for patients with larger and deep ulcers in the ileum. These findings may have implications for recruitment into clinical trials and would support the importance of balancing these prognostic factors in trial arms. Further prospective data are needed to validate these findings.

Multivariate analyses of MRI findings for predicting osteomyelitis of the foot in diabetic patients

There have been no previous magnetic resonance imaging (MRI) studies using multivariable analysis to diagnose osteomyelitis in patients with diabetic foot. To retrospectively investigate the MRI findings of osteomyelitis in patients with diabetic foot using multivariate analyses. From November 2015 to March 2018, 118 patients who underwent MRI of the foot to evaluate suspected osteomyelitis were included in this study. The patients were categorized into the presence or absence of osteomyelitis. The primary and secondary MRI findings were retrospectively reviewed. To identify independent predictive MRI findings, multivariate analyses with binary logistic regression and receiver operating characteristic curve analyses were performed including all 118 patients and 93 patients presenting decreased T1 signal intensity, respectively. T1 signal intensity, T1 marrow pattern, T1 marrow distribution, T2 signal intensity, concordance of marrow signal intensity, cortical interruption, ulcer depth, abscess, and wet gangrene were significantly different between the two groups (P < 0.05). Multivariate analyses indicated that fluid equivalent T2 signal intensity, deep ulcer, and confluent T1 marrow pattern were major factors associated with osteomyelitis. The area under the curve of predicted probabilities for the combination of these factors was 0.799 across all 118 patients and 0.761 across 93 patients with decreased T1 signal intensity. Confluent T1 marrow pattern is a reliable finding to suggest osteomyelitis in patients with diabetic foot. In addition, fluid equivalent T2 signal intensity and deep ulcer are important findings that may suggest osteomyelitis, irrespective of T1 signal intensity change.

Combination treatment with light emitting diode and wound dressings in a patient with a venous leg ulcer: a case report

Leg ulcers are a problem often found in the adult population, with a prevalence of 1 to 2% in the population. Vascular disease is the most common cause. Venous disorders that occur in the lower limbs are the main cause of lower leg ulcers compared to other vascular disorders. Emerging wounds can cause pain, thereby interfering with quality of life. These conditions often persist for a long time, and they can be a health problem that leads to an economic burden as a result of a long period of wound care. Several therapeutic methods that can be chosen for wound healing purposes include light-emitting diodes (LED) and wound dressings. LED can have physiological effects such as anti-inflammatory resolution, neoangiogenesis, fibroblast and epithelial proliferation, and collagen synthesis and deposition. Furthermore, wound dressings provide an optimal condition for wound healing by creating a moist and clean environment for the wound. We present the case of a 47-year-old man with a venous leg ulcer that was treated with LED and wound dressings. After the patient underwent the eighteenth LED session, combined with wound dressings, the size, depth, and pain of the venous leg ulcer decreased.

The assessing scale for assessment of chronic Grade II diabetic foot ulcer healing

Background: Lysine is a basic amino acid which is not integrated inside the body. It is integrated in higher plants through biochemical pathways. Numerous clinical studies have revealed that amino acids assume a significant part in rushing the way toward wound recuperating by improving the nearby blood supply as growth factors. Aim and Objectives: This investigation intended to evaluate the wound healing potential, efficacy, and tolerability of lysine cream (15%) in diabetic foot ulcer assessed by assessing scale. Materials and Methods: A randomized, open-label, and interventional study was directed on 40 subjects (participants) with diabetic ulcers. Participants were grouped into two groups, control and test. The control group (n = 20) was treated with standard treatment and the test group was treated with standard treatment alongside lysine cream (15%) twice every day. Wound healing in the participants was assessed by the assessing scales. Results: A total of 40 participants were allotted into two groups. The results expressed as mean ± standard deviation values imply the size and depth of the foot ulcer from the 1st week to the 8th week. Both the groups showed a significant increase the ulcer healing and decrease the pressure of foot ulcer of over a period of 8 weeks. The assessment of the 1st week showed no significant ulcer healing and its pressure. The overall outcome indicated that the lysine-treated group extensively reduced each of the parameters favoring wound healing than the standard therapy alone (control group). Furthermore, there was no significant difference in the blood glucose levels in both study groups. Conclusion: Treatment with additional lysine cream considerably improved wound recovery in diabetic foot ulcer patients when compared to the standard therapy alone.

Predictors of occult lymph node metastasis in cutaneous head and neck melanoma.

ObjectiveTo use the Surveillance, Epidemiology, and End Results (SEER) database to verify the findings of a recent National Cancer Database (NCDB) study that identified factors predicting occult nodal involvement in cutaneous head and neck melanoma (CHNM) while identifying additional predictors of occult nodal metastasis and comparing two distinct cancer databases.MethodsCases of CHNM in the SEER database diagnosed between 2004 and 2014 were identified. Demographic information and oncologic data were obtained. Univariate and multivariate analysis were performed to identify factors associated with pathologic nodal positivity.ResultsThere were 34002 patients with CHNM identified. Within this population, 16232 were clinically node-negative, 1090 of which were found to be pathologically node-positive. On multivariate analysis, factors associated with an increased risk of occult nodal metastasis included increasing depth of invasion (stepwise increase in adjusted odds ratio [OR]), nodular histology (aOR: 1.47 [95% CI: 1.21–1.80]), ulceration (aOR: 1.74 [95% CI: 1.48–2.05]), and mitoses (aOR: 1.86 [95% CI: 1.36–2.54]). Factors associated with a decreased risk of occult nodal metastasis included female sex (aOR: 0.80 [0.67–0.94]) and desmoplastic histology (aOR: 0.37 [95% CI: 0.24–0.59]). Between the SEER database and the NCDB, factors associated with occult nodal involvement were similar except for nodular histology and female sex, which did not demonstrate significance in the NCDB.ConclusionRegarding clinically node-negative CHNM, the SEER database and the NCDB have similarities in demographic information but differences in baseline population sizes and tumor characteristics that should be considered when comparing findings between the two databases.Level of evidence4.

Factors Affecting Hospital Length of Stay in Patient with Diabetic Foot Ulcer

Background. Foot ulcer is one of the most common complications in diabetes mellitus patients. This condition prolongs hospital length of stay (LOS) and increases hospitalization cost. This study aims to assess factors that affect the LOS in patients with the mentioned condition.&#x0D; Methods. This is a retrospective cohort study of diabetes mellitus patients with foot ulcer who were hospitalized in Cipto Mangunkusumo General Hospital from January 2015 to April 2016. There were 120 patients recruited and then divided into two groups according to their hospitalization duration, which was short and long. Univariate analysis was conducted in predicted factors including gender, ankle-brachial index, ulcer size, ulcer depth, leukocyte count, treatment, cardiovascular comorbidity, blood pressure, smoking history, septicemia, ketoacidosis, hypoalbuminemia, and upper respiratory tract infection. Chi-Square tests were performed to analyze the association of those factors with LOS. The odds ratio of each variable was evaluated using logistic regression analysis.&#x0D; Result. In this study, the mean of LOS was 26 days (2 – 87 days). Factors that significantly correlated with LOS were ankle-brachial index (p 0.041, OR 2.275, CI 95 % 1.025 – 5.041), ulcer size (p 0.044, OR 3.038, CI 95 % 1.032 – 9.942), smoking history (p 0.022, OR 2.434, CI 95 % 1.125 – 5.265), sepsis (p &lt; 0.001, OR 4.240, CI 95 % 1.908 – 9.423), and ketoacidosis (p &lt; 0.001, OR 8.611, CI 95 % 3.396 – 21.835) In multivariate analysis, the most significant factor was ketoacidosis (p &lt; 0.001, OR 8.360, CI 95 % 3.209 – 21.780).&#x0D; Conclusion. Ketoacidosis is the most significant factor that prolonged hospital stays in a patient with diabetic foot ulcer.&#x0D; Keywords: Diabetic foot ulcer, Length of stay

Effectiveness of topical insulin in the management of diabetic foot ulcers.

Introduction: Diabetes mellitus is one of the most common metabolic disorders affecting a large part of our population. Apart from its effect on all organ systems, these metabolic derangements affect other processes in the body as well. Diabetic wounds are difficult to treat with conventional treatments. Delayed wound healing has led to increased morbidity and mortality in the population. Increased blood glucose leads to ineffective angiogenesis and less collagen deposition. In various studies long acting insulin zinc suspension has been shown to augment wound healing without any harmful effects. Objectives: To find out the advantages of topical insulin in the management of diabetic foot ulcers. Study Design: Observational study. Setting: Plastic Surgery and General Surgery Department, Baqai Medical University Karachi. Period: January 2014 to December 2016. Material and Methods: Patients visiting the Surgical OPD with diabetes mellitus and concomitantly having foot ulcers were included in the study. Diabetics having blood glucose levels of 110-130 gm/dl and ulcers measuring more than one cm on the dorsum of the foot were included in the study. All patients having foot ulcers were treated by daily topical spray of 1cc saline mixed with 5 units of insulin. This treatment was continued for 12 weeks or till the time ulcer was completely healed (whichever was earlier) and ulcer size was measured weekly. Ulcer size and depth before and after treatment was measured. Results: We had a total of 65 participants, among them there were 52 males and 13 females presenting with diabetic foot ulcer. Around 87.6% (n=57) patients had type 2 diabetes mellitus whereas 12.3% (n=8) patients had type 1 diabetes mellitus. Upon examination of the patient the location, size and depth of the ulcer was measured as well. These parameters were measured before and after treatment by topical insulin spray. Right foot ulcers were present in 64.6% of the patients and 35.38% patients had left foot ulcers. The mean size and depth of ulcer was 5.1 + 1.1 cm2 and 8.7 + 0.12 mm respectively. After treatment the mean size and depth of ulcer was found to be 1 + 0.04cm2 and 1.4 + 0.12mm respectively. Conclusion: There was significant improvement after treatment of diabetic foot ulcers with topical insulin spray. The wound size and depth were considerably decreased. This treatment had more promising results than conventional treatment methods for diabetic foot ulcers.

Therapeutic Effect of a Traditional Chinese Medicine on the Treatment of Painful Leg Ulcer

This study aimed to investigate the therapeutic effect of a traditional Chinese medicine on the treatment of painful leg ulcer. Twelve cases of painful leg ulcer were recruited and their characteristics (etiology, size, Visual Analog Scale score, and duration) were recorded. Then, an herbal medicine-oriented treatment protocol combining Zhi Tong Sheng Ji powder (ZTSJ) and SJXP (Sheng Ji Xiang Pi plaster) was applied to these patients. The results suggested that this therapeutic protocol contributed to pain relief and promoted wound healing simultaneously. Specifically, 2 days after applying ZTSJ on wounds, the intensity of pain reduced substantially, and the difference between pre- and post-treatment Visual Analog Scale scores (46 mm vs 23 mm, P < .001) was statistically significant. Epithelialization varied according to ulcer depth. If the wound was deep to the fascia, islands of epithelia did not form within wounds, but rather formed at the edge of wounds, generating island of epithelial cells (IECs) or newly formed epithelial tissue. If the wound was superficial and the dermis remained, scattered IECs appeared within ulcers and merged eventually. Furthermore, as wound pain decreased, IECs appeared, expanded, and merged, or epithelial proliferation and migration occurred in wound margin, eventually healing wounds. No infection spread, topical rashes, itching, or other allergies occurred in these 12 cases, and the time for recovery ranged from 16 to 163 days. ZTSJ is effective for the treatment of painful leg ulcers, but the specific mechanism is not clear.