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.

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.

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.

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 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.

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.

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.

Role of inflammatory markers in the healing time of diabetic foot osteomyelitis treated by surgery or antibiotics.

OBJECTIVE: To analyse the predictive role of inflammatory markers in the healing time of diabetic foot osteomyelitis treated by surgery or antibiotics. METHODS: An observational study of patients with diabetic foot ulcers (DFU) and clinically suspected osteomyelitis. The patients underwent surgical or antibiotic treatment for bone infection in a specialised diabetic foot unit. Blood samples were taken from each patient to analyse biomarkers. The main outcome was the number of weeks until healing occurred. RESULTS: A total of 116 patients took part in the study. The number of weeks until healing was similar for both groups (surgical n=96 and antiobiotic n=20, treatments). No association was observed among biomarkers as predictors of time-to-healing. CONCLUSION: There is not enough evidence to define the prognostic role of inflammatory markers in the healing time of DFUs complicated with diabetic foot osteomyelitis, regardless of the treatment administered.

Early Foot Structural Changes After Lateral Column Exostectomy in Patients With Charcot Foot.

Although exostectomy for chronic midfoot plantar ulcers in Charcot foot is apparently effective, with healing rates of nearly 75%, a subset of patients develop recurrent ulceration and show an unstable foot position, especially after undergoing exostectomy confined to the lateral column. The reasons for this failure have not been investigated. The main objective of this study was to evaluate the early changes in radiographic alignment after an exostectomy in patients with Charcot neuropathic osteoarthropathy (rocker bottom) and plantar ulcer located in the lateral column. The present study evaluated retrospectively changes in radiographic alignment after an exostectomy in 12 Charcot feet (rocker bottom) with plantar ulcer located in the lateral column. Indication for plantar exostectomy was the treatment of ulcer affected by osteomyelitis. We evaluated the early changes in the alignment of the foot on weight-bearing lateral radiographs 6 months after exostectomy. Paired sample Wilcoxon test was used to calculate the differences between preoperative and postoperative measurements. Furthermore, the relationship between revision surgery and early changes in radiographic angular measurements was determined by using the Mann-Whitney U test. After exostectomy, the inclination of the calcaneal bone decreased (P = .003; r = 0.849) and declination of talus bone increased (P = .041; r = 0.589). The change in calcaneal inclination was associated with revision surgery (P = .042; r = 0.586). The present case series demonstrates that exostectomy procedure for the lateral column in patients with Charcot foot results in radiological changes in the hindfoot over the sagittal plane. The inversion of the calcaneal pitch angle suggests the possibility of further adverse events and the need for revision surgery.

To Smoke or Not To Smoke: Cigarettes Have a Negative Effect on Wound Healing of Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) have a complex pathophysiology and require an expert multidisciplinary treatment. There are several, both systemic and local, risk factors for DFUs. A recent meta-analysis of 18 studies has now provided robust evidence on the detrimental effect of smoking on healing of DFUs. Indeed, healing rates were consistently lower among smokers than among nonsmokers. Based on this new evidence, it is reasonable to consider the utility of smoking cessation programs. Incorporation of the latter into the holistic therapeutic strategy for DFUs may be anticipated to improve healing rates, but this remains to be shown.

Analysis of Ulcer Recurrences After Metatarsal Head Resection in Patients Who Underwent Surgery to Treat Diabetic Foot Osteomyelitis.

Metatarsal head resection is a common and standardized treatment used as part of the surgical routine for metatarsal head osteomyelitis. The aim of this study was to define the influence of the amount of the metatarsal resection on the development of reulceration or ulcer recurrence in patients who suffered from plantar foot ulcer and underwent metatarsal surgery. We conducted a prospective study in 35 patients who underwent metatarsal head resection surgery to treat diabetic foot osteomyelitis with no prior history of foot surgeries, and these patients were included in a prospective follow-up over the course of at least 6 months in order to record reulceration or ulcer recurrences. Anteroposterior plain X-rays were taken before and after surgery. We also measured the portion of the metatarsal head that was removed and classified the patients according the resection rate of metatarsal (RRM) in first and second quartiles. We found statistical differences between the median RRM in patients who had an ulcer recurrence and patients without recurrences (21.48 ± 3.10% vs 28.12 ± 10.8%; P = .016). Seventeen (56.7%) patients were classified in the first quartile of RRM, which had an association with ulcer recurrence (P = .032; odds ratio = 1.41; 95% confidence interval = 1.04-1.92). RRM of less than 25% is associated with the development of a recurrence after surgery in the midterm follow-up, and therefore, planning before surgery is undertaken should be considered to avoid postsurgical complications.

Conservative Surgery of Diabetic Forefoot Osteomyelitis: How Can I Operate on This Patient Without Amputation?

Surgery is necessary in many cases of diabetic foot osteomyelitis. The decision to undertake surgery should be based on the clinical presentation of diabetic foot osteomyelitis. Surgery is required when the bone is protruding through the ulcer, there is extensive bone destruction seen on x-ray or progressive bone damage on sequential x-ray while undergoing antibiotic treatment, the soft tissue envelope is destroyed, and there is gangrene or spreading soft tissue infection. Several issues should be taken into account when considering surgery for treating diabetic foot osteomyelitis. It is necessary to have a surgeon available with diabetic foot expertise. Regarding location of diabetic foot osteomyelitis, it is important to consider whether isolated bone or a joint is involved. In cases in which osteomyelitis is associated with a bone deformity, surgery should be able to correct this. The surgeon should always reflect about whether extensive/radical surgery could destabilize the foot. The forefoot is the most frequent location of diabetic foot osteomyelitis and is associated with better prognosis than midfoot and hindfoot osteomyelitis. Many surgical procedures can be performed in patients with diabetes and forefoot ulcers complicated by osteomyelitis while avoiding amputations. Performing conservative surgeries without amputations of any part of the foot is not always feasible in cases in which the infection has destroyed the soft tissue envelope. Attempting conservative surgery in such cases risks infected tissues remaining in the wound bed leading to failure. The election of different surgical options depends on the expertise of the surgeons selected for the multidisciplinary teams. It is the aim of this article to provide a sample of surgical techniques in order to remove the bone infection from the forefoot while avoiding amputations.

The influence of the length of the first metatarsal on the risk of reulceration in the feet of patients with diabetes.

Our aim was to identify the optimal diagnostic cutoff point on the scale of protrusion measurements of the first metatarsal (M1) to predict the probability of reulceration after metatarsal head resection in patients with diabetes mellitus. We conducted a prospective study of patients with diabetes who underwent resection of at least 1 metatarsal head in our department. After surgery, we measured the difference in length (protrusion) between the M1 and the longest of the 4 lesser metatarsals by radiographic view. The patients were divided into those in whom the M1 was the longest of the 5 metatarsals (group 1) and patients in whom at least one of the lesser metatarsals was longer than the M1 (group 2). They were followed-up for 12 months and were assessed for reulceration. Ninety-one patients were included in the present study: 43 (47%) in group 1 and 48 (53%) in group 2. In group 1, the longer the protrusion of M1 was, the higher the probability for reulceration (P < .001, 95% confidence interval = 0.813-0.997). In group 2, the shorter the protrusion of M1, the higher the probability for reulceration (P = .002, 95% confidence interval = 0.628-0.905). The optimal cutoff point for group 1 was 11 mm (sensitivity = 84.6%, specificity = 86.7%) for the probability of reulceration. In group 2, it was -7 mm (sensitivity = 81.8%, specificity = 65.4%). These results suggest that M1 protrusion is an optimum prognostic indicator for reulceration and could be recommended for detecting patients at risk of reulceration after surgery.