Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL) is an extremely rare autosomal dominant progeroid disorder caused by pathogenic variants in POLD1. Because MDPL shares many clinical features with Werner syndrome (WS), distinguishing between the two disorders can be challenging. We report a Japanese man with genetically confirmed MDPL caused by the recurrent POLD1 p.Ser605del variant, highlighting its distinctive cutaneous manifestations. The patient exhibited mandibular hypoplasia, limb-predominant lipodystrophy, skin atrophy, painful plantar clavi and calluses, and later developed prominent telangiectasias. Radiographs at the initial presentation revealed multiple extraosseous calcifications in the lower leg, followed by the development of a refractory skin ulcer over the same calcified region. Computed tomography confirmed calcifications within the subcutaneous tissue and skeletal muscle. To our knowledge, soft-tissue calcification and refractory skin ulceration have not previously been reported in MDPL. Although MDPL shares substantial clinical overlap with WS, it can be distinguished by its earlier onset, preserved scalp hair, prominent telangiectasias, sensorineural hearing loss, an absence of cataracts, and a lack of a recognized predisposition to malignancy. This case expands the cutaneous spectrum of MDPL and emphasizes the dermatological clues that facilitate its differentiation from WS.

Background/Objectives: CEAP C6 venous leg ulcers are the most resource-intensive stage of chronic venous disease, yet short-term prognostication at admission remains empirical. We aimed to determine which routinely available admission variables are associated with unfavourable in-episode evolution and to develop a concise prognostic model. Methods: Single-centre retrospective observational cohort of 87 consecutive patients; in-episode evolution (favourable versus unfavourable) was documented in 59. Associations were tested by univariate methods and binary logistic regression. Because outcome was undocumented in 32.2% of the cohort, a tipping-point sensitivity analysis quantified the departure from a missing-at-random mechanism required to nullify each association. Results: Wound infection was recorded in 69.0% of patients, with Pseudomonas spp. and meticillin-sensitive Staphylococcus aureus predominating. Evolution was unfavourable in 34/59 patients (57.6%) and was associated with wound infection (OR 7.00, 95% CI 2.13-23.03), microbial eczema, multiple ulceration and urban residence, but with neither the neutrophil-to-lymphocyte ratio (p = 0.920) nor any individual comorbidity. In the final model, wound infection (OR 6.10), urban residence (OR 5.81) and multiple ulceration (OR 5.01) were independently associated with outcome (Nagelkerke R2 = 0.405; AUC 0.812, 95% CI 0.704-0.919). Sensitivity analysis showed the wound infection association to be robust to informative missingness, whereas urban residence was the most fragile. Conclusions: Wound-level factors-infection and multiple ulcers-carried more short-term prognostic information than comorbidity burden or systemic inflammatory indices. These findings are hypothesis-generating and require external validation.

Leg ulcers are a debilitating complication of sickle cell disease (SCD, including sickle cell anaemia and other sickle cell disorders) and have no proven treatments. Resolution of Sickle Cell Leg Ulcers with Voxelotor (RESOLVE) was a Phase 3, randomised, double-blind, placebo-controlled trial evaluating voxelotor for leg ulcer resolution in participants aged ≥12 years with SCD (homozygous haemoglobin S [HbSS]/haemoglobin S β[0]-thalassaemia [HbSβ[0]]) and ≥1 active cutaneous lower-extremity ulcer. Participants from Kenya, Nigeria and Brazil were randomised 1:1 to voxelotor 1500 mg (N = 45) or placebo (N = 43) for 12 weeks. The primary end-point, complete resolution of all target ulcer(s) at Week 12, was not met (achieved resolution: voxelotor 6.7% [3/45], placebo 7.0% [3/43]; two-sided p > 0.99). After Week 12, both groups received open-label voxelotor. During this period, dosing was paused in May 2024, when preliminary data from four voxelotor trials, including RESOLVE, showed safety signals and potential risks that required further analysis. The trial was discontinued in September 2024 when voxelotor was withdrawn from all markets globally. In final safety analyses for RESOLVE, the most common SCD-related treatment-emergent adverse event (TEAE) was sickle cell anaemia with crisis (randomised period: voxelotor 44.4%, placebo 25.6%; open-label period: continuing-voxelotor 60.5%, delayed-voxelotor 53.5%). Eleven participants had fatal events, nine when receiving voxelotor and two after voxelotor was paused (one after ~1 week; one after ~4 months); no deaths were considered treatment-related. In conclusion, leg ulcer resolution was similar between groups, and the voxelotor arm had a higher rate of TEAEs.

Chronic venous disease (CVD) causes substantial symptom burden and healthcare cost, driven not only by venous hypertension but by a persistent molecular cascade of endothelial activation, glycocalyx degradation, and inflammation within the vein wall. Venoactive drugs (VADs) - a heterogeneous class of flavonoid, synthetic, animal-derived, and plant-derived compounds - target this cascade and are recommended by international guidelines as adjuncts to compression therapy, endovenous intervention, and wound care in venous leg ulcer (VLU) management. This review synthesizes the pharmacological rationale and clinical evidence for VADs across these three adjunct settings. The evidence base is strongest for VAD use alongside compression, supported by multiple Cochrane-grade meta-analyses; MPFF and ruscus extracts have the most robust symptom evidence, while MPFF, pentoxifylline, and sulodexide have the strongest evidence for VLU healing. Evidence in the peri-interventional setting remains the weakest, limited to open-label studies of MPFF. Priorities for future research include stratified and biomarker-guided prescribing, combination pharmacotherapy, and larger, adequately powered VLU healing trials.

The comorbidity of chronic venous insufficiency is a prevalent vascular disorder that has further risks of progressing to ulceration and recurrent symptoms despite prior intervention. Endovenous laser therapy (EVLT) has become a first-line treatment for chronic venous insufficiency, especially in the axial great saphenous vein (GSV) reflux due to its high technical success and favorable safety profile. However, the recurrence of venous reflux remains clinically significant and often requires repeat imaging and intervention to further manage the condition. We present the case of a 54-year-old female patient with a history of chronic deep vein thromboses and prior EVLT of the right GSV who developed recurrent axial reflux associated with lateral malleolar ulceration. With duplex ultrasound mapping, we were able to demonstrate near-continuous reflux in the proximal GSV with incompetent accessory and perforator veins. Overall, this case report highlights the importance of comprehensive venous duplex imaging in identifying the mechanisms of recurrence and guiding management decisions, including the consideration of cyanoacrylate closure versus repeat thermal ablation.

Slow healing and recurrent venous leg ulcers resulting from varicose veins due to lower limb chronic venous insufficiency are common vascular complications. If left untreated, they may lead to severe outcomes such as hemorrhage and, in extreme cases, limb amputation. We report the case of a 61-year-old male with bilateral lower limb varicosities of 10 years' duration, presenting with multiple painful venous leg ulcers that recurred several months after phlebectomy due to patient non-compliance. Physical examination revealed exquisitely tender, exudative, irregular-bordered, multiple shallow ulcers with sloping edges and a putrid odor. The surrounding tissue was oedematous and indurated, predominantly involving the areas in and around the ankle joints. Aerobic wound swab culture showed heavy growth of Klebsiella pneumoniae and Proteus hauseri, with moderate growth of Staphylococcus aureus and Streptococcus pyogenes. One month of Ayurvedic intervention employing vrana sodhana and vrana ropana cikitsa resulted in accelerated wound healing in recurrent, acute-on-chronic, non-healing venous leg ulcerations.

To determine whether heel-free compression bandaging is non-inferior to heel-wrapped bandaging for maintaining interface pressure in adults with venous leg ulcers. Randomised, controlled, parallel-group, non-inferiority trial. Adults with open venous leg ulcers (CEAP C6) treated at a French university hospital were randomised to heel-free or heel-wrapped (control) bandaging for 4-6 weeks. The primary outcome was interface pressure 48 h after the final bandage application, analysed in the per-protocol population. Secondary outcomes were ankle oedema, change in interface pressure and patient preference. Of 102 randomised patients, 85 were included in the per-protocol analysis. At V3, mean interface pressure was 30.1 mmHg in the heel-free group and 28.4 mmHg in the control group (difference, 1.7 mmHg; 95% CI, -1.3 to 4.6), meeting the non-inferiority criterion. After adjustment for baseline circumference and sex, ankle circumference was 1.7 cm lower in the heel-free group (95% CI, -3.35 to 0.04). Among 48 patients who had experienced both techniques, 23 (47.9%) preferred heel-free bandaging. Heel-free bandaging was non-inferior to heel-wrapped bandaging for interface pressure at 48 h. The technique may be considered when compatible with ulcer location and patient preference; effects on healing and adherence require further study. Trial Registration: NCT04046120.

This supplement was supported by Essity AB, Sweden. The authors received honoraria for their contributions. Essity AB could provide feedback on product-related content, with implementation at the authors' discretion.