Does HPV biotype influence the characteristics and evolution of plantar warts?

BACKGROUND: Few studies have addressed the relationship of human papillomavirus (HPV) biotypes to patient characteristics and the clinical signs, course, and response to the treatment of plantar warts. OBJECTIVE: Analyze the HPV types associated with plantar warts and their relationship with warts characteristics, patient characteristics and response to treatment. METHODS: A total of 372 patients sampled for hyperkeratosis of a plantar wart were included. Multiplex polymerase chain reaction (PCR) was performed to detect the HPV biotype. RESULTS: The prevalence of HPV was 81.2%, and HPV1 was the most prevalent biotype (36.1%). HPV1 was the most prevalent biotype in patients < 70 years old (90.9% in < 10 years), and biotypes 2, 19 and 27 were the most prevalent in patients > 70 years old (p = 0.012). HPV1 was the most frequent in patients with one (39,9%) or two (47.1%) warts and HPV5 (33.3%) in patients with three warts (p < 0.001). Cure, spontaneous resolution, and recurrence were higher in HPV1 (p < 0.001). HPV14 warts healed the fastest (2 months quartile 1-3 (2.0-2.0)), and HPV5 (10.977 (6.0-20.0)) and HPV27 (7.5 (3.0-10.0)) warts (p = 0.033) took the longest to heal. CONCLUSIONS: HPV biotype is associated with age and the number of warts and appears to influence the natural history of warts and their response to treatment.

Cryotherapy versus topical nitric-zinc complex solution for the treatment of plantar warts: A randomized controlled trial.

Cryotherapy is commonly regarded as the primary treatment method for plantar warts. A new medical device called nitric-zinc complex solution (NZCS) has also emerged as a potential alternative for wart treatment. The main aim of this study was to analyze and compare the effectiveness of cryotherapy using liquid nitrogen and NZCS in treating plantar warts. We conducted a randomized and controlled clinical trial involving patients with plantar warts. A total of 62 patients were enrolled in the study and monitored for 12 weeks or until their warts were completely resolved. The patients received either cryotherapy or NZCS, with a maximum of six treatment applications. The cure rate was 65.5% in the group treated with cryotherapy and 56.6% in the group treated with NZCS. The average number of treatment applications required for curing warts was significantly lower in the cured group (3.28 ± 1.63) than in the group with unresolved warts (5.5 ± 1.27) (p < 0.01). Moreover, the average number of applications was lower in the cryotherapy group (3.6 ± 1.8) than in the NZCS group (4.8 ± 1.8) (p < 0.01). Based on the findings, NZCS could be considered a favorable first-line treatment option for plantar warts.

Comparative Analysis of Bone Resection Versus Bone Curettage in Diabetic Foot Osteomyelitis.

This study aims to describe the healing times of patients who underwent bone resection compared to bone curettage for managing diabetic foot osteomyelitis and to compare short- and long-term complications. This analytical retrospective observational cohort study collected clinical records of patients from a specialized diabetic foot clinic who underwent resection or bone curettage between January 2017 and January 2022. After surgery, a 1-year follow-up was conducted to record healing times and short- and long-term complications. The study included thirty-one patients, with 19 (61.29%) undergoing resections and 11 (38.71%) undergoing bone curettages. The resection cohort had a mean healing time of 5.70 ± 6.05 weeks, whereas the curettage cohort had a mean healing time of 14.45 ± 11.78 weeks, showing a statistically significant difference (P = 0.011). No significant differences were observed in terms of short- and long-term complications. In the resection cohort, 12 (63.20%) experienced short-term complications, compared to eight (66.70%) in the curettage cohort (P = 0.842, χ2 = 0.40, OR = 1.16). In the resection cohort, n = 6 (31.60%) had long-term complications, while n = 3 (25.00%) in the curettage cohort experienced long-term complications (P = 0.694, χ2 = 0.155, OR = 0.72). Although there were no significant differences in short- and long-term complications between resection and curettage, the resection group showed shorter healing times.

Analysis of the Influence of Diabetic Nephropathy in Patients with Diabetic Foot Osteomyelitis.

This study analyzed the influence of diabetic nephropathy on the healing prognosis after conservative surgery in diabetic foot osteomyelitis (DFO). A retrospective observational study was carried out between January 2021 and December 2022 and involved 278 outpatients with a diagnosis of DFO at a specialized diabetic foot unit, including 74 (26.62%) patients with DN (group 2) and 204 (73.38%) patients without DN (group 1). There were 266 (95.70%) ulcers on the forefoot, 8 (2.90%) on the midfoot, and 4 (1.45%) on the hindfoot (p = 0.992). The healing rates were 85.1% (n = 63) for group 2 and 81.3% (n = 165) for group 1 (p = 0.457). When exploring the influence of DN on the risk of delayed ulcer healing, the results did not show a significant effect [12 (6; 28) weeks among patients with DN vs. 12 (6; 21) weeks among patients without DN; p = 0.576]. No significant differences were observed in complications, with one (2.59%) death occurring in group 1 (p = 0.296) and three minor amputations being performed in both groups [two (5.13%) amputations in group 1 vs. one amputation (9.09%) in group 2; p = 0.217]. Bone cultures were performed for a total of 190 patients (133 in group 1 and 57 in group 2). Of these, 176 positive bone cultures were isolated: 71 positive bone cultures (57.7%) were monomicrobial cultures in group 1, with 30 (56.6%) in group 2. There were 52 (42.3%) that had at least two microorganisms in group 1, and 23 (43.4%) in group 2 (p = 0.890). The most frequently prescribed oral antibiotic was amoxicillin/clavulanate (43.89%), followed by levofloxacin (28.4%), and trimethoprim/sulfamethoxazole (14.7%). This study shows that DN does not have a significant influence on the healing prognosis of patients with DFO after conservative surgery.

Culture Concordance in Different Sections of the Metatarsal Head: Interpretations of Microbiological Results.

Microbiological cultures of per-wound bone biopsies have shown a lack of correlation and a high rate of false-negative results when compared with bone biopsy cultures in diabetic foot osteomyelitis. The selection of samples from the area of active osteomyelitis, which contains a complete census of the microorganisms responsible for the infection, is essential to properly guide antimicrobial treatment. We aimed to comparatively evaluate the quantitative and qualitative cultures taken from different areas, in metatarsal heads resected for osteomyelitis. For this purpose, we consecutively selected 13 metatarsal heads from 12 outpatients with plantar ulcers admitted to our diabetic foot unit. Metatarsal heads were divided transversally into 3 portions: plantar (A), central (B), and dorsal (C), and the 39 resulting samples were cultured. Qualitative and quantitative microbiological analysis was performed, and the isolated species and bacterial load, total and species specific, were compared between the 3 metatarsal bone segments. The primary outcome of the study was the bacterial diversity detected in the different bone sections. Cultures were positive in 12 of the 13 included metatarsal heads (92%). A total of 34 organisms were isolated from all specimens. Ten of the 12 cultures (83%) were polymicrobial. Ten of the 13 metatarsal heads (77%) had identical microbiological results in each of the 3 bone sections. The largest number of microorganisms was found in the central section. The overall concordance between sections was 91%. The predominant microorganisms were coagulase-negative staphylococci (41%). Statistical differences were not found in the bioburden between sections (range 3.25-3.41 log10 colony-forming unit/g for all sections; P = .511). The results of our study suggest that microorganisms exhibit a high tendency to spread along the metatarsal bone and that the degree of progression along the bone is species dependent. The central portions of metatarsal bones tend to accumulate a higher diversity of species. Thus, we recommend this area of bone for targeted biopsy in patients with suspected osteomyelitis.

The Influence of Arterial Calcification on Clinical Outcomes in Patients with Diabetic Foot Ulcer Complicated by Osteomyelitis Treated by Surgery.

The aim of our study was to analyze the influence of radiographic arterial calcification (RAC) on clinical outcomes and wound healing in patients with diabetic foot ulcers complicated by osteomyelitis treated by surgery. We analyzed retrospectively the clinical records of 102 patients with diabetic foot osteomyelitis who underwent surgery at a specialized diabetic foot unit between January 2014 and December 2016. The clinical data of evolution until its complete epithelialization and a follow-up 1 year were reviewed, and after reviewing the radiological images, patients were classified into 2 groups: those with RAC and those without RAC. We analyzed several clinical features in both groups. The presence of RAC was associated with a greater time of healing (10.68 ± 7.24 vs 8.11 ± 4.50 weeks; P = .029) and shorter time to recurrence and reulceration (13.30 ± 9.25 vs 18.81 ± 11.63 weeks; P = .036). However, this association was not found for patients with mild and moderate peripheral artery disease (PAD), whose time of healing was 8.97 ± 4.51 weeks compared to 9.16 ± 6.39 weeks for patients without PAD; P = .864. The time of healing of diabetic foot ulcers complicated by osteomyelitis treated by surgery can be negatively affected by the presence of RAC even more than by the presence of mild and moderate ischemia. The presence of RAC may offer clinical guidance at the level of primary care though this would need thorough validation in future studies.

Cantharidin-Podophyllin-Salicylic Acid Formulation as a First-Line Treatment for Plantar Warts? A Case Report with Multiple Plantar Warts of Human Papillomavirus Biotype 27 and Previous Failed Treatments.

BACKGROUND Plantar warts are benign skin tumors caused by the human papillomavirus (HPV). There are multiple treatments, but none ensure absolute success. Successful treatment depends on several factors, such as the location, number of lesions, HPV biotype, and the patient's health condition. This report presents a 53-year-old woman who had multiple recalcitrant plantar warts with HPV biotype 27 that were treated using a cantharidin-podophyllin-salicylic acid (CPS) formulation after 2 failed treatments. CASE REPORT A 53-year-old woman was seen on October 25, 2021. She had 6 plantar warts due to HPV biotype 27, which was confirmed by polymerase chain reaction using a sample of hyperkeratosis scales obtained from the wart after debridement. Five cryotherapy sessions were applied, without clinical improvement. Two sessions of nitric-acid-zinc complex were then applied, from which the patient reported severe pain, without clinical improvement. Finally, 3 sessions of CPS formulation were applied, and the HPV remitted in all warts. CONCLUSIONS Conservative treatments, such as cryotherapy, have not been effective in a case of multiple recalcitrant plantar warts. The combined action of the 3 compounds of CPS formulation was key in the resolution of this case. Plantar wart treatment should be easy to apply, effective, fast, and efficient. In cases of recalcitrant or numerous warts, treatment should be more aggressive from the beginning if the patient's lifestyle allows it. It would be interesting to conduct randomized clinical trials to find out which patients could be indicated for the CPS formulation as a first line of treatment.

Safety and Efficacy of Several Versus Isolated Prophylactic Flexor Tenotomies in Diabetes Patients: A 1-Year Prospective Study.

Background: To assess long-term clinical outcomes of patients who underwent isolated versus several percutaneous flexor tenotomies for the treatment of toe deformities and previous diabetic foot ulcers; Methods: Twenty-three patients (mean age 66.26 ± 11.20, years) who underwent prophylactic percutaneous flexor tenotomies secondary to tip-toe ulcers participated in this 1-year prospective study. The study was stratified into two groups for analyses: (1) isolated tenotomies patients, and (2) several tenotomies patients (two or more tenotomies). Outcome measures were toe reulceration and recurrence, minor lesions, digital deformities, and peak plantar pressure (PPP­N/cm2) and pressure/time Integral (PTI­N/cm2/s) in the hallux and minor toes after a 1-year follow-up period; Results: Patients with isolated tenotomies (n = 11, 35.48%) showed a higher rate of reulceration (n = 8, 72.7%, p < 0.001) in the adjacent toes, additionally, we found more prevalence of hyperkeratosis (n = 11, 100%), minor lesions (n = 9, 81%), and claw toes (n = 11, 100%) (p < 0.001). In several tenotomies patients (n = 20, 64.52%), we found a higher rate of floating toes (n = 16, 80%) in comparison with isolated tenotomies patients (p < 0.001). PPP and PTI in the non-tenotomy toes were higher in the group of patients who underwent isolated tenotomies (p < 0.001); Conclusions: Patients who underwent several tenotomies had better clinical outcomes after a 1-year follow-up period compared to isolated tenotomies.

Are Digital Arthroplasty and Arthrodesis Useful and Safe Surgical Techniques for the Management of Patients with Diabetic Foot?

OBJECTIVE: To analyze and compare the development of short- and long-term complications in patients with diabetic foot after digital arthroplasty or arthrodesis. METHODS: The authors reviewed patient records from January 2017 to March 2020. Patients were treated by digital arthroplasty or arthrodesis to correct toe deformity (elective or prophylactic surgery), achieve ulcer healing in toes (curative surgery), or manage toe infection (emergent surgery). During 1-year follow-up, researchers registered short- and long-term complications. Researchers analyzed the association between the type of surgery and the development of short- and long-term complications. RESULTS: Forty-four patients (83.0%) received arthroplasty, and nine (17.0%) received arthrodesis. The mean time to heal from ulcers was 5.2 ± 5.2 weeks. A significant association was observed between arthrodesis and the development of long-term complications (P = .044; odds ratio, 5.1; 95% confidence interval, 0.9-27.2). No differences were observed between type of surgery and short- or long-term complications. Moreover, both short- and long-term complications were related to longer time to heal (respectively, 7.6 ± 6.0 vs 2.1 ± 0.5 weeks, P < .001; and 6.3 ± 6.2 vs 4.2 ± 4.0 weeks, P = .039). CONCLUSIONS: Digital arthroplasty or arthrodesis are good options for managing patients with diabetic foot who require digital deformity correction to achieve digital ulcer healing or management of diabetic foot infection in phalanges.

Clinical and Histological Outcomes of Negatively Charged Polystyrene Microspheres Applied Daily Versus Three Times per Week in Hard-to-Heal Diabetic Foot Ulcers: A Randomized Blinded Controlled Trial.

Negatively charged polystyrene microspheres (NCMs) have been demonstrated as a novel and effective therapy for managing hard-to-heal diabetic foot ulcers (DFUs). However, one limitation of this therapy is that the protocol is based on daily application, which sometimes does not fit local protocols of wound care. Thus, we aimed to analyze the safety and efficacy of a new dose regimen. We conducted a randomized blinded controlled trial in a specialized diabetic foot unit between May 2019 and February 2021 with a total of 30 patients who had neuropathic or neuroischemic DFUs that had not responded after four weeks of standard treatment. Patients were randomized consecutively into a group that received daily application (control) or one that received applications three times per week (experimental). The clinical outcomes were evaluated using the Wollina score and wound-area reduction (WAR) weekly during a treatment period of 28 days. The histological outcomes were assessed using a soft-tissue punch biopsy (3 mm) at 0, 14, and 28 days to evaluate cellular proliferation. The Wollina scores were higher at the end of treatment by week 4 in both groups, but the differences were not significant between groups. The averages were 6 (5, 7) points in Experimental group (EG) and 6 (6,7) points in Control group (CG) (p = 0.848). Wound area reduction at day 28 was 53.57 [37.43, 79.16] % in the CG and 79.37 [42.74, 93.57] % in the EG, without differences among groups (p = 0.305). Cellular proliferation was similar in both groups at day 28. Application three times per week showed similar clinical and histological outcomes to those of daily application, both dose regimens demonstrated significant improvement of granulation tissue formation and WAR during the treatment.

Efficacy of cryotherapy for plantar warts: A systematic review and meta-analysis.

Recent systematic reviews of plantar warts continue to consider cryotherapy as one of the treatments of choice, but this method appears to have lower cure rates than alternative treatments. A systematic review using meta-analyses of the efficacy of cryotherapy in plantar warts treatment was performed. Systematic electronic searches were conducted. The primary endpoint was complete clearance of plantar warts. Risk-of-bias assessment was based on Cochrane Handbook recommendations. Meta-analyses used Review Manager v5.4.1 software. Cryotherapy appears to have lower cure rates than other treatments (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.12-0.78) with substantial heterogeneity (I2  = 80%). A second subgroup analysis had low heterogeneity (I2  = 28.2%). Subgroup analysis showed that plantar wart cure rates were significantly lower with cryotherapy compared to the physical treatment group (OR 0.05, 95% CI 0.01-0.49) with substantial heterogeneity (I2  = 79%), and antiviral, chemotherapy, and retinoid group (OR 0.30, 95% CI 0.14-0.66) without heterogeneity (I2  = 0%). Intralesional versus spray-on cryotherapy appears to be more effective (OR 0.21, 95% CI 0.09-0.48). No difference in efficacy between two rounds of 10-s and four rounds of 5-s freeze-thaw cycles in cryotherapy was found. Evidence of the superiority of antivirals and chemotherapy over cryotherapy in the treatment of plantar warts was found. However, no evidence supports the superiority or inferiority of cryotherapy compared to other treatments.

A comparison of hyperspectral imaging with routine vascular noninvasive techniques to assess the healing prognosis in patients with diabetic foot ulcers.

OBJECTIVE: To compare the potential healing prognosis of the different routine noninvasive techniques implemented in the International Working Group Diabetic Foot Guidelines with the novel use of hyperspectral imaging (HSI) in patients with diabetic foot ulcers (DFUs). METHODS: Twenty-one patients with active DFUs participated in this 1-year prospective study in a specialized diabetic foot unit between December 2018 and January 2020. HSI was performed at baseline to quantify tissue oxygenation and should be presented on an anatomical map by analyzing the following parameters: (1) oxygen saturation of the hemoglobin, (2) tissue hemoglobin index, (3) the near-infrared perfusion index, and (4) tissue water index. In addition, transcutaneous oxygen pressure (TcpO2), systolic toe and ankle pressures, ankle-brachial index, and toe-brachial index values were calculated for the ulcerated limb. The primary outcome measure was wound healing, defined as complete epithelization without any drainage confirmed for at least 10 days after closure was first documented at 24 weeks. RESULTS: During the follow-up period 14 patients (66.66 %) healed and 7 patients did not heal (33.3%) by 24 weeks. The TcpO2 optimal cut-off point as determined by a balance of sensitivity and specificity of 28.5 mm Hg that yielded a sensitivity of 91% and a specificity of 100%, and area under the curve of 0.989 (P = .005; 95% confidence interval [CI], 0.945-1.000). Followed by the oxygen saturation of the hemoglobin optimal cut-off point as determined by a balance of sensitivity and specificity of 48.5 mm Hg that yielded a sensitivity of 93% and a specificity of 0.71%, and area under the curve of 0.932 (P = .013; 95% CI, 0.787-1.000). The logistic regression analyses showed that TcpO2 was the only variable associated with wound healing at 24 weeks (P < .001; 95% CI, 0.046-0.642). CONCLUSIONS: The HSI was shown to be effective in the prognosis of DFU healing compared with other noninvasive test; only TcpO2 values resulted in better diagnosis potential in wound healing.

A non-invasive method for diagnosing plantar warts caused by human papillomavirus (HPV).

The methods that are used for the diagnostic confirmation of human papillomavirus (HPV) include excisional biopsy and histopathological studies or polymerase chain reaction (PCR). They are invasive, laborious, and subject to ethical restrictions due to the benign nature of these warts. This study aims to analyse the accuracy of noninvasive swab samples to diagnose plantar warts. Fifty plantar warts were included in the study. Skin swabs and hyperkeratosis skin scales were collected from each wart. Multiplex PCR was performed to detect and type the HPVs. The prevalence of HPV in this study was 90% when the sample was obtained using the wart scraping method and 94% when it was obtained using swabs and the new method. In 45 of the 45 positive samples (sensitivity: 100%), the result between the wart scab and wart swab were almost identical. The genotyping result was identical in all 46 patients who had a positive result using both methods. The swab method appears to be a simple and accurate technique to diagnose plantar warts due to HPV. It is a noninvasive technique that could be performed even by inexperienced professionals and in patients with pain or a fear of needles.

Analysis of Plantar Pressure Pattern after Metatarsal Head Resection. Can Plantar Pressure Predict Diabetic Foot Reulceration?

To evaluate the metatarsal head that was associated with the highest plantar pressure after metatarsal head resection (MHR) and the relations with reulceration at one year, a prospective was conducted with a total of sixty-five patients with diabetes who suffered from the first MHR and with an inactive ulcer at the moment of inclusion. Peak plantar pressure and pressure time integral were recorded at five specific locations in the forefoot: first, second, third, fourth, and fifth metatarsal heads. The highest value of the four remaining metatarsals was selected. After resection of the first metatarsal head, there is a displacement of the pressure beneath the second metatarsal head (p < 0.001). Following the resection of the minor metatarsal bones, there was a medial displacement of the plantar pressure. In this way, plantar pressure was displaced under the first metatarsal head following resection of the second or third head (p = 0.001) and under the central heads after resection of the fourth or fifth metatarsal head (p < 0.009 and p < 0.001 respectively). During the one-year follow-up, patients who underwent a metatarsal head resection in the first and second metatarsal heads suffered transfer lesion in the location with the highest pressure. Patients who underwent a minor metatarsal head resection (second-fifth metatarsal heads) showed a medial transference of pressure. Additionally, following the resection of the first metatarsal head there was a transference of pressure beneath the second metatarsal head. Increase of pressure was found to be a predictor of reulceration in cases of resection of the first and second metatarsal heads.

Diagnostic Accuracy of Bone Culture Versus Biopsy in Diabetic Foot Osteomyelitis.

OBJECTIVE: To compare the diagnostic accuracy of bone culture (microbiology) and biopsy (histology) in patients with acute or chronic diabetic foot osteomyelitis (DFO). METHODS: This cross-sectional study involved patients for whom providers had a clinical suspicion of DFO. Two bone samples were taken: one for microbiologic testing and another for histologic testing. The sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio were calculated for bone culture results in relation to the probability of DFO diagnosis. RESULTS: Fifty-two patients were included; 69% had positive bone culture results, and 90.4% had positive histology results (P = .013), and of those 90.4%, 25.5% had acute and 74.5% had chronic DFO. The sensitivity of the microbiologic bone culture result was 0.70, the specificity was 0.40, the positive predictive value was 0.92, and the negative predictive value was 0.13. CONCLUSIONS: Histology provides more accurate diagnosis of DFO than microbiology, especially for patients with chronic DFO. These patients could be underdiagnosed because of false-negative results provided by bone culture. Providers should perform both tests to confirm the presence of DFO.

Conservative surgery for chronic diabetic foot osteomyelitis: Procedures and recommendations.

Osteomyelitis (OM) is the most frequent infection associated with diabetic foot ulcers (DFU) that typically involve the forefoot, the most common location of DFU. Conservative surgical procedures could be attractive alternative that reduces minor and major amputations and avoid future recurrence thus preserving the functionally of the foot. This review aimed to analyze and describe the current evidence on conservative diabetic foot osteomyelitis (DFO) surgical procedures depending on DFU location and indications. A narrative revision of the evidence was carried out by searching Medline through PubMed databases from inception to late July 2020 to identify retrospective, prospective, and randomized controlled trials pertaining to conservative DFO procedures on the forefoot. Seven types of conservative surgical procedures for DFO treatment in the forefoot are described in this review: (1) partial or total distal phalangectomy, (2) arthroplasty of the proximal or distal interphalangeal joint, (3) distal Syme amputation, (4) percutaneous flexor tenotomy, (5) sesamoidectomy, (6) arthroplasty of the metatarsophalangeal joint, and (7) metatarsal head resection. When indicated, conservative surgery for DFUs in patients with chronic forefoot OM is a safe and effective option that increases the chances of healing and reduces the possibility of limb loss and death compared with radical amputation procedures. Since a lack of sufficient evidence supporting this procedure exists, future investigations should be focused on the random clinical trial (RCT) design. The results of prospective trials could help surgeons select the appropriate procedure in each case in order to minimize complications.

Topical treatment for plantar warts: A systematic review.

There are a wide variety of treatments for plantar warts, but none has been shown to be effective in all patients. We aimed to perform a systematic review of the efficacy of different topical treatments on plantar warts. Systematic electronic searches (Pubmed, Cochrane Library, Embase, and Web of Science) were conducted in April 2020. Meta-analyses, systematic reviews, and retrospective or prospective clinical trials of the effects of topical and nonsurgical treatments of plantar warts were included. Two authors performed the study selection and data extraction. Any discrepancies between the two reviewers were discussed with a third reviewer. Forty-four studies were included. The average cure rates of the most frequent treatments were variable across the studies: cryotherapy (45.61%), salicylic acid (13.6%), cantharidin-podophyllin-salicylic acid formulation (97.82%), laser (79.36%), topical antivirals (72.45%), intralesional bleomycin (83.37%), and intralesional immunotherapy (68.14%). Twenty-two studies (50%) had a level of evidence 1b and grade of recommendation A, five studies (11.4%) had a level of evidence 2b and grade of recommendation B, two studies (4.5%) had a level of evidence 3b and grade of recommendation B, and 15 studies (34,1%) with a level of evidence 4 and grade of recommendation C. First-choice treatments for common warts, such as cryotherapy and salicylic acid, have low-cure rates for plantar warts. Other treatments, such as CPA formulation, immunotherapy, and intralesional bleomycin, which have compassionate use, have higher cure rates. This review should stimulate future high-quality research to evaluate these specialized treatments.

Mortality in Patients with Diabetic Foot Ulcers: Causes, Risk Factors, and Their Association with Evolution and Severity of Ulcer.

Background: This study reviews the mortality of patients with diabetic foot ulcers (DFU) from the first consultation with a Multidisciplinary Diabetic Foot Team (MDFT) and analyzes the main cause of death, as well as the relevant clinical factors associated with survival. Methods: Data of 338 consecutive patients referred to the MDFT center for a new DFU during the 2008-2014 period were analyzed. Follow-up: until death or until 30 April 2020, for up to 12.2 years. Results: Clinical characteristics: median age was 71 years, 92.9% had type 2 diabetes, and about 50% had micro-macrovascular complications. Ulcer characteristics: Wagner grade 1-2 (82.3%), ischemic (49.2%), and infected ulcers (56.2%). During follow-up, 201 patients died (59.5%), 110 (54.7%) due to cardiovascular disease. Kaplan-Meier curves estimated a reduction in survival of 60% with a 95% confidence interval (95% CI), (54.7-65.3) at 5 years. Cox regression analysis adjusted to a multivariate model showed the following associations with mortality, with hazard ratios (HRs) (95% CI): age, 1.07 (1.05-1.08); HbA1c value < 7% (53 mmol/mol), 1.43 (1.02-2.0); active smoking, 1.59 (1.02-2.47); ischemic heart or cerebrovascular disease, 1.55 (1.15-2.11); chronic kidney disease, 1.86 (1.37-2.53); and ulcer severity (SINBAD system) 1.12 (1.02-1.26). Conclusion: Patients with a history of DFU have high mortality. Two less known predictors of mortality were identified: HbA1c value < 7% (53 mmol/mol) and ulcer severity.

Adipose-Derived Mesenchymal Stem Cells in the Treatment of Diabetic Foot Ulcers: A Review of Preclinical and Clinical Studies.

This review provides an outline of the use of adipose-derived mesenchymal stem cells (AMSCs) in the treatment of diabetic foot ulcers (DFUs). A systematic search of PubMed and the Cochrane database was performed on October 2, 2019. Eighteen studies were identified (14 preclinical and 4 clinical). Studies in animal models have demonstrated that AMSCs enhance diabetic wound healing, accelerate granulation tissue formation, and increase reepithelialization and neovascularization. Only 1 randomized control trial has been published so far. Patients (n = 25) with DFUs were treated using an allogeneic AMSC directly on the wound bed as a primary dressing, and improvements were found in complete wound closure in the treatment group (n = 16). Three clinical studies showed that autologous AMSC might be a safe alternative to achieve therapeutic angiogenesis in patients with diabetes and peripheral arterial disease. Based on the available evidence, AMSCs hold promise in the treatment of DFUs. However, this evidence requires confirmation by well-designed trials. Additional studies are also required to understand some issues regarding this treatment for DFUs. For example, the potential application of autologous or allogeneic AMSCs in different types of DFUs, optimal dose/infusion schedules, safety evaluations, and cost-effectiveness.