This study aimed to assess the efficacy of human amniotic membranes (HAM) in treating venous and diabetic ulcers, which often pose challenges in healing. A systematic review and meta-analysis were conducted, evaluating 10 relevant studies involving 633 participants. Findings revealed that HAM treatment significantly accelerated ulcer closure, demonstrating over 90% complete healing compared to standard care. Despite moderate heterogeneity among studies, the results strongly suggested the effectiveness and safety of HAM therapy for venous and diabetic leg ulcers. Further research with larger study cohorts is recommended to bolster the existing evidence supporting HAM in managing these challenging wounds.

We present the case of an 83-year-old woman with leg ulcers who was diagnosed with sarcoidosis. This case highlights the importance for clinicians to consider ulcerative sarcoidosis when encountering patients with leg ulcers along with hilar adenopathy, uveitis, elevated serum angiotensin-converting enzyme, and histopathological findings of epithelioid cell granulomas.

UNASSIGNED: Sickle-cell diseases (SCD) are a group of hereditary disorders in which a specific mutation in the gene that encodes the hemoglobin ß chain leads to formation of an anomalous hemoglobin molecule (HbS) with high polymerization power. This leads to sickling of erythrocytes in situations of low oxygen tension, such as in microcirculation, resulting in peripheral microvasculature occlusion, chronic hemolysis, inflammation, and damage to several target organs. Malleolar ulcers are among the most-debilitating complications of the disease, as they are associated with significant pain, secondary infections, and social impact due to their aesthetic impairment. There are no completely satisfactory therapeutic options for this complication; local healing agents, antibiotics, and dressings are used, with high rates of recurrence and complications, such as osteomyelitis and even limb amputation.
UNASSIGNED: This case study evaluated the effect of Traditional Chinese Medicine techniques on chronic malleolar ulcers in a 49-year-old male patient. Ten sessions of systemic acupuncture (combinations involving Source, Master, Energetic Action, and Extraordinary Vessels points), auriculotherapy, and dressing with magnets were conducted.
UNASSIGNED: Although the primary outcome sought was not reached (decrease in ulcer diameters), this patient had great reduction of local pain, a decrease in limb edema, and important reduction of his inflammatory condition, reflected in his decreasing blood levels of C-reactive protein.
UNASSIGNED: These results show that acupuncture should be considered as an important auxiliary treatment for SCD complications.

Leg ulcers are a common and often serious problem in older adults. Underlying conditions that increase risk include age-related increases in chronic venous insufficiency, peripheral artery disease, connective tissue and autoimmune conditions, reduced mobility, and diabetes mellitus (DM). Geriatric patients have a higher risk of multiple wound-related complications including infection, cellulitis, ischemia, and gangrene, any of which may lead to further complications including amputation. The very presence of these lower extremity ulcers in the elderly negatively impacts their quality of life and ability to function. Understanding and early identification of the underlying conditions and wound features are important for effective ulcer healing and complication mitigation. This targeted review focuses on the three most common types of lower extremity ulcers: venous, arterial, and neuropathic. The goal of this paper is to characterize and discuss the general and specific aspects of these lower extremity ulcers and their relevancy and impact on the geriatric population. The top five main results of this study can be summarized as follows. (1) Venous ulcers, caused by inflammatory processes secondary to venous reflux and hypertension, are the most common chronic leg ulcer in the geriatric population. (2) Arterial-ischemic ulcers are mainly due to lower extremity vascular disease, which itself tends to increase with increasing age setting the stage for an age-related increase in leg ulcers. (3) Persons with DM are at increased risk of developing foot ulcers mainly due to neuropathy and localized ischemia, both of which tend to increase with advancing age. (4) In geriatric patients with leg ulcers, it is important to rule out vasculitis or malignancy as causes. (5) Treatment is best made on a case-by-case basis, considering the patient\'s underlying condition, comorbidities, overall health status, and life expectancy.

Time-driven activity-based costing (TDABC) is suggested to assess costs within the value-based healthcare approach, but there is a paucity of applications in chronic diseases such as deep vein thrombosis (DVT) and leg ulcers. In this context, we applied TDABC in a cost-effectiveness analysis comparing venous stenting to compression ± anticoagulation (standard of care-SOC) from both hospital and societal perspectives in Italy. TDABC was applied to both treatments to assess costs that were included in a cost-effectiveness model. Clinical inputs were retrieved from the literature and integrated with real-world data. The Incremental Cost Utility Ratio (ICUR) of stenting compared to SOC was EUR 10,270/QALY and EUR 8962/QALY for hospital and societal perspectives, respectively. The mean cost per patient for venous stenting of EUR 5082 was higher than the Diagnosis-Related Group (DRG) reimbursement (EUR 4742). For SOC, an ulcer healing in 3 months costs EUR 1892, of which EUR 302 (16%) is borne by the patient versus a reimbursement of EUR 1132. TDABC showed that venous stenting may be cost-effective compared with SOC but that reimbursement rates may not completely cover the real costs, which are partially sustained by the patients. A more efficient policy for covering the real costs may be beneficial for both clinical centers and patients.

Elevated levels of inflammatory mediators-including the interleukin IL-23-are implicated in the pathogenesis of pyoderma gangrenosum (PG), an autoinflammatory neutrophilic dermatosis characterized by rapidly enlarging, suppurative ulcers and cribriform scarring. Here, we present the first case report of significant response of isolated ulcerative PG with tildrakizumab, a biologic agent directed against the p19 subunit of IL-23, in an elderly woman with extensive treatment-refractory PG on her left leg. Tildrakizumab (100 mg subcutaneously at weeks 0 and 4, then every 8 weeks, and eventually increased in frequency to every 6 weeks), combined with acetic acid soaks each morning and chemical debridement every evening with 3% hydrogen peroxide, resulted in progressive decrease in ulcer size and depth, re-epithelialization, and recovery of sensory perception. This report describes the dramatic clinical response of ulcerative PG on the leg with tildrakizumab.

BACKGROUND: Prolidase deficiency (PD) is an autosomal recessive inborn multisystemic disease caused by mutations in the PEPD gene encoding the enzyme prolidase D, leading to defects in turnover of proline-containing proteins, such as collagen. PD is categorized as a metabolic disease, but also as an inborn error of immunity. PD presents with a range of findings including dysmorphic features, intellectual disabilities, recurrent infections, intractable skin ulceration, autoimmunity, and splenomegaly. Despite symptoms of immune dysregulation, only very limited immunologic assessments have been reported and standard therapies for PD have not been described. We report twin females with PD, including comprehensive immunologic profiles and treatment modalities used.
METHODS: Patient 1 had recurrent infections in childhood. At age 13, she presented with telangiectasia, followed by painful, refractory skin ulcerations on her lower limbs, where skin biopsy excluded vasculitis. She had typical dysmorphic features of PD. Next-generation sequencing revealed pathogenic compound heterozygous mutations (premature stop codons) in the PEPD gene. Patient 2 had the same mutations, typical PD facial features, atopy, and telangiectasias, but no skin ulceration. Both patients had imidodipeptiduria. Lymphocyte subset analysis revealed low-normal frequency of Treg cells and decreased frequency of expression of the checkpoint molecule CTLA-4 in CD4+ TEM cells. Analysis of Th1, Th2, and Th17 profiles revealed increased inflammatory IL-17+ CD8+ TEM cells in both patients and overexpression of the activation marker HLA-DR on CD4+ TEM cells, reflecting a highly activated proinflammatory state. Neither PD patient had specific antibody deficiencies despite low CD4+CXCR5+ Tfh cells and low class-switched memory B cells. Plasma IL-18 levels were exceptionally high.
CONCLUSIONS: Immunologic abnormalities including skewed frequencies of activated inflammatory CD4+ and CD8+ TEM cells, decreased CTLA-4 expression, and defects in memory B cells may be a feature of immune dysregulation associated with PD; however, a larger sample size is required to validate these findings. The high IL-18 plasma levels suggest underlying autoinflammatory processes.

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The presence of leg ulcers in individuals with sickle cell disease often represents an early sign of vasculopathy and future end organ damage. Pathophysiological mechanisms of formation and evolution of leg ulcers are poorly understood; nevertheless, HbF has been associated with lower incidence of leg ulcers, while hydroxyurea has been correlated with high risk of leg ulcers. As a result, there is hesitation regarding hydroxyurea use in patients with SCD and leg ulcers. In this study, we aim to define (1) a target of HbF that offers protection against leg ulcer development and (2) the impact of hydroxyurea therapy on leg ulcer prevalence. Our study demonstrated that in order to reduce leg ulcer incidence by one-third, a HbF > 25% is needed, a threshold not commonly reached and maintained in the adult SCD population. Importantly, leg ulcer incidence appears to be independent of HU use (p = 0.50). Our interpretation of this data is that the use of HU in a patient with SCD and leg ulcers should be guided by a careful assessment of risks and benefits of this therapeutic modality.

UNASSIGNED: Patient adherence to wearing compression stockings in the management of chronic venous insufficiency (CVI) and venous leg ulcers (VLUs) is low. Poor adherence with compression stockings contributes to recurrence and impaired healing of VLUs. As such, the purpose of this review was to report on the scientific evidence related to adherence and explore modifiable factors which impact adherence with compression stockings.
UNASSIGNED: A systematic search was conducted from inception to 31 October 2019. Following the PRISMA-ScR Checklist, PubMed, Medline, CINAHL, Cochrane, Embase, OT Seeker and Web of Science were explored using search terms: compression/compression stocking/compression garment/compression sock/stockings/garments and adherence/compliance/concordance.
UNASSIGNED: We identified 2613 papers of which 125 full text papers were assessed for eligibility and 69 met inclusion criteria. Papers were grouped and charted by concepts relevant to the research questions and narratively synthesized. Several dominant themes emerged, and a conceptual framework was developed incorporating modifiable variables, adherence itself, and outcomes related to adherence. Specifically considering interventions to improve adherence, only five of 14 randomized controlled trials were able to demonstrate improvements in adherence through unidimensional approaches. All nine of the case studies/series demonstrated a positive impact on adherence, eight of which described a personalized multidimensional approach. A lack of consensus around defining, measuring, and quantifying adherence with compression stockings was identified, resulting in wide variation in reported adherence rates.
UNASSIGNED: Inconsistency in the definition and measurement of adherence limits meaningful interpretation of the literature. No individual intervention has consistently demonstrated improved adherence. Multidimensional interventions show promise but require further investigation with high-quality trials. Improving adherence appears to improve health outcomes in VLU /CVI populations but there is a lack of information directly linking improved adherence with cost outcomes.
UNASSIGNED: Open Science Framework: ACTRN12620000544976p.