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Intratumoral delivery of mRNA encoding immunostimulatory molecules can initiate a robust, global antitumor response with little side effects by enhancing local antigen presentation in the tumor and the tumor draining lymph node. Neoantigen-based mRNA nanovaccine can inhibit melanoma growth in mice by intratumoral injection. Myeloid-derived suppressor cells (MDSCs) suppress antitumor immune responses by secreting immunosuppressive agents, such as reactive oxygen species (ROS). Suppression of STAT3 activity by stattic may reduce MDSC-mediated immunosuppression in the TME and promote the antitumor immune responses. In this study, in vitro transcribed mRNA encoding tumor antigen survivin was prepared and injected intratumorally in BALB/c mice bearing subcutaneous colon cancer tumors. In vivo studies demonstrated that intratumoral survivin mRNA therapy could induce antitumor T cell response and inhibit tumor growth of colon cancer. Depletion of CD8 + T cells could significantly inhibit survivin mRNA-induced antitumor effects. RT-qPCR and ELISA analysis indicated that survivin mRNA treatment led to increased expression of receptor activator nuclear factor-κB ligand (RANKL). In vitro experiment showed that MDSCs could be induced from mouse bone marrow cells by RANKL and RANKL-induced MDSCs could produce high level of ROS. STAT3 inhibitor stattic suppressed activation of STAT3 and NF-κB signals, thereby inhibiting expansion of RANKL-induced MDSCs. Combination therapy of survivin mRNA and stattic could significantly enhance antitumor T cell response, improve long-term survival and reduce immunosuppressive tumor microenvironment compared to each monotherapy. In addition, combined therapy resulted in a significantly reduced level of tumor cell proliferation and an obviously increased level of tumor cell apoptosis in CT26 colon cancer-bearing mice, which could be conducive to inhibit the tumor growth and lead to immune responses to released tumor-associated antigens. These studies explored intratumoral mRNA therapy and mRNA-based combined therapy to treat colon cancer and provide a new idea for cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Due to the challenge for intratumoral administration, innate agonists have not made it beyond preclinical studies for efficacy testing in most tumor types. Pancreatic ductal adenocarcinoma (PDAC) has a hostile tumor microenvironment that renders T cells dysfunctional. Innate agonist treatments may serve as a T cell priming mechanism to sensitize PDACs to anti-PD-1 antibody (a-PD-1) treatment. Using a transplant mouse model with spontaneously formed liver metastasis, a genetically engineered KPC mouse model that spontaneously develops PDAC, and a human patient-derived xenograft model, we compared the antitumor efficacy between intrahepatic/intratumoral and intramuscular systemic administration of BMS-986301, a next-generation STING agonist. Flow cytometry, Nanostring, and cytokine assays were used to evaluate local and systemic immune responses. This study demonstrated that administration of STING agonist systemically via intramuscular injection is equivalent to its intratumoral injection in inducing both effector T cell response and antitumor efficacy. Compared to intratumoral administration, T cell exhaustion and immunosuppressive signals induced by systemic administration were attenuated. Nonetheless, either intratumoral or systemic treatment of STING agonist was associated with increased expression of CTLA-4 on tumor-infiltrating T cells. However, the combination of a-PD-1 and anti-CTLA-4 antibody with systemic STING agonist demonstrated the antitumor efficacy in the KPC mouse spontaneous PDAC model. The mouse pancreatic and liver orthotopic model of human patient-derived xenograft reconstituted with PBMC also showed that antitumor and abscopal effects of both intratumoral and intramuscular STING agonist are equivalent. Taken together, this study supports the clinical development of innate agonists via systemic administration for treating PDAC., (© 2024. The Author(s).)

Background: In patients with a high recurrence risk after treatment for Dupuytren contracture (DC) by Collagenase Clostridium histolyticum (CCH), adjuvant medical therapy may improve the outcome. Non-steroidal anti-inflammatory drugs have been used in the treatment of similar fibroproliferative processes. The aim of this study was to investigate if adjuvant anti-inflammatory medication could improve the outcome of CCH treatment for DC. Methods: In a prospective double blinded randomised trial, the effect of adjuvant peroral celecoxib on the outcome of DC treated with CCH was investigated in 32 patients with a high fibrosis diathesis. Primary outcome was the increase in Total Passive Extension Deficit (TPED)/ray. Secondary outcomes were the TPED of the individual finger joints, Tubiana index, Disability of Arm, Shoulder and Hand score (DASH) and visual analogue scale (VAS) for pain and satisfaction. Results: A significantly greater improvement in the celecoxib group for TPED and metacarpophalangeal contracture was found. For the proximal interphalangeal joint, the effect was much less pronounced. The VAS for pain and satisfaction were better at 6 and 12 weeks in the celecoxib group. The other outcome parameters did not significantly differ between both groups. Conclusions: Adjuvant peroral administration of celecoxib might improve the gain in TPED after treatment with CCH in patients with DC and a high fibrosis diathesis, with a beneficial effect up to 24 months. Level of Evidence: Level II (Therapeutic).

Keloid scars are a particularly challenging fibroproliferative wound healing disorder with a variety of proposed management approaches including concurrent surgery and intralesional steroid injection. We aimed to identify the optimum time for triamcinolone injection of keloids, by comparing the recurrence and complication occurrence in patients who received pre-, intra- or post-operative injection. Studies reporting on the rate of recurrence and complication occurrence following treatment of keloid scarring with concurrent surgical excision and intralesional steroid injection were identified from the PubMed, Web of science and Embase databases. The I-squared (I 2 ) statistic was used to quantify the variability in study estimates due to heterogeneity and to determine whether the fixed or random effect models will be employed. Publication bias was visualized through funnel plots and tested with the Egger's test. We found that the recurrence rate was significantly lower with post-operative injection compared to intra-operative injection (p < 0.001) and pre-operative injection (p = 0.009). A significant difference between intra-operative and pre-operative injection was not found (p = 0.46). In conclusion, post-operative steroid injection after surgical excision results in lower keloid recurrence compared to pre- and intra-operative injection.Level of Evidence IV "This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .", (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

In-transit metastasis (ITM) develop in approximately 1 in 10 patients with melanoma and the disease course can vary widely. Surgical resection is the gold-standard treatment; however, ITM are often surgically unresectable due to size, distribution, and/or anatomic involvement. Oncolytic viral therapies are one category of non-surgical treatment options available for ITM. They induce tumor cell lysis and systemic anti-tumor activity through selective infection of tumor cells by naturally occurring or genetically modified factors. While there are numerous oncolytic viral therapies in various stages of development for the treatment of ITM, this discussion focuses on the mechanism and available literature for the two most established herpes virus-based therapies., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Treatment of scarring has long been a problem due to high incidence and recurrence. Despite many existing treatment therapies, the efficacy remains unstable., Objectives: To determine the efficacy and safety of skin biopsy punch in combination with corticosteroid injection (BPCI) in treating keloids., Approach: This was a retrospective study. In total, 16 patients with keloids received BPCI. Changes in scar appearance, accompanied symptoms, and Vancouver Scar Scale (VSS) were analyzed. Patient satisfaction, VAS scores, and adverse effects were also evaluated., Results: Scar appearance, accompanied symptoms, and VSS scores improved significantly after the treatment. The total effective rate was 93.75% at an 18-month follow-up on average. The mean reduction rate of VSS score was 58.44% (p < 0.0001), especially in height and pliability (84.44% and 78.19%, p < 0.0001). The recurrence rate in this study was 12.5% (n = 2) at an 18-month follow-up on average. Mild adverse effects of pain, pruritus, hypopigmentation, and telangiectasia were recorded., Conclusions: This study demonstrated BPCI might be an effective and safe therapy in keloids with a low long-time recurrence rate and well tolerance for patients., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Electrochemotherapy (ECT) combines the reversible electroporation (rEP) with intravenous (i.v.) or intratumoral (i.t.) administration of chemotherapeutic drugs. We conducted this study to compare the efficacy of i.v., i.t., and i.v. + i.t. injection of bleomycin (BLM) in ECT treatment of colorectal hepatic metastases in a rat model. WAG/Rij rats were randomized into three groups and underwent ECT with i.v., i.t., or i.v. + i.t. injection of BLM. Tumor volumes and oxygenation were measured by means of ultrasound and photoacoustic imaging. Moreover, liver and tumor tissue were analyzed by histology and immunohistochemistry. The i.v. and i.v. + i.t. groups exhibited a 44.0% and 46.6% reduction in oxygen saturation of the tumor tissue when compared to pretreatment values, whereas the i.t. group only showed a reduction of 35.2%. The extent of tumor tissue necrosis did not statistically differ between the groups. However, the i.t. group showed a tendency towards a lower necrosis rate. Cell proliferation, apoptotic cell death, vascularization, and immune cell infiltration were comparable in the treated tumors of the three groups. ECT with i.v. administration of BLM should be preferred in clinical practice, as the combined i.v. + i.t. therapy did not show superior oncological outcomes in the present study., (© 2024. The Author(s).)

Ranula is a mucous cyst that occurs in the sublingual gland (SLG) in the floor of the mouth. It can be classified into two types based on origins: One is the the lesser sublingual gland (LSLG) in the anterior segment and the Rivini duct, which is connected to it, and the other is the greater sublingual gland (GSLG) in the posterior segment. Because of the anatomical characteristics, surgical resection of the cysts carries the risk of damaging adjacent tissues and has a high recurrence rate. Intralesional injection of sclerotherapy may be a better alternative treatment. We summarized 65 cases of ranula treated with intralesional injections of bleomycin(BML). According to the origin of the ranula, 60 cases were from the LSLG and the Rivini duct, and 5 cases were from the GSLG. The results showed that 60 cases of ranula from LSLG and Rivini ducts were 100% cured during the follow-up period. The median number of injections for all patients was 1.16. All 5 cases of ranula from the GSLG did not wholly recover. This study confirmed that BLM intralesional injection is a safe and effective treatment modality for cysts from LSLG or the ducts of Rivini rather than GSLG. Therefore, before treatment, it is necessary to determine the type and origin of the cyst by characterizing its morphology to ensure the effectiveness of the treatment., (© 2024. The Author(s).)

Objective: To analyze the efficacy of intralesional steroid treatment in refractory caustic esophageal stricture., Materials and Methods: An analytical, retrospective study of patients receiving intralesional steroid treatment with triamcinolone acetonide as a result of refractory caustic esophageal stricture was carried out. Demographic variables, stricture characteristics, number of dilations, steroid injections, and dilation score (no. of dilations/follow-up period in months) pre- and post-treatment were collected. Stricture characteristics (diameter and length) and dilation score pre- and post-treatment were compared using the T-Test or Wilcoxon test., Results: N= 5. Median age: 5 years (17 months-7 years). Follow-up: 6.60 ± 2.70 years. Swallowed products included NaOH, KOH, and ClH. Zargar classification at follow-up initiation was IIb (n= 2), IIIa (n= 1), and two chronic strictures. 6.6 ± 9.23 esophageal dilations were carried out before steroid treatment initiation. The mean number of intralesional therapy sessions was 11.20 ± 6.14. Stricture length decreased by 3.60 ± 2.63 cm (t= 3.06; p= 0.019). No differences were found in terms of diameter increase: -1.60 ± 3.58 mm (t= -1.00; p= 0.187). The dilation score diminished from 1.47 ± 0.86 to 0.47 ± 0.18 dilations per month of follow-up (Z= -2.02; p= 0.043)., Conclusions: Even though there is limited evidence available in the pediatric population, intralesional triamcinolone treatment is seemingly useful in the treatment of refractory caustic esophageal stricture, since it reduces length and dilation score.

The application of Botulinum toxin (Masport) in urology has a long history. We aimed to assess the effect of local Masport on improvement in patients with urethral stricture by reducing the recurrence of urethral stricture. This pilot study conducted was a double-blind randomized clinical trial with code IRCT20191222045852N1 on patients suffering from urethral stricture. Finally, 28 patients were allocated to intervention and control groups. Twelve patients received intralesional injection with Masport in addition to internal urethrotomy, while 16 patients underwent internal urethrotomy with normal saline. The Cox regression hazard model was used to evaluate the effect of treatment status on recurrence time adjusted for the age, length, and location of the stenosis, cause of the stenosis, and history of previous operations. The effect of treatment type was significant at the .05 level. The past medical history and cause of urethral stricture had a significant impact on relapse-free survival. Also, the improvement in the mean score of the EuroQol Visual Analogue Scale (EQ-VAS), International Prostate Symptom Score (IPSS), and Q-max in the group with Masport was significantly different from the group with normal saline. The internal urethrotomy with intralesional injection of Masport has a better survival prognosis than internal urethrotomy with normal saline group. Therefore, the authors suggest that, given this successful initial clinical trial, consideration be given to future studies involving the use of botox in the management of urethral strictures in conjunction with internal urethrotomy., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Nail psoriasis is associated with significant disease burden, negative impact on quality of life, and potential progression to psoriatic arthritis. Initiating timely and appropriate treatment is of the utmost importance, especially because nail disease may be more resistant to therapies than cutaneous psoriasis. This article reviews available intralesional, topical, and systemic treatment options for nail psoriasis, and discusses efficacy and safety of studied agents. Also reviewed are consensus treatment guideline recommendations. An updated algorithm to aid physicians in selection of specific treatment options is provided., Competing Interests: Disclosure Mr J.K. Hwang and Dr S.R. Lipner have no conflicts of interest to disclose. Dr S.R. Lipner has served as a consultant for Ortho-Dermatologics, BelleTorus Corporation, Eli Lilly, and Moberg Pharmaceuticals. Mr J.K. Hwang has no financial disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Recent approaches for recurrent respiratory papillomatosis including local injection of bevacizumab and HPV vaccination show promise in reducing the need for frequent surgeries. In this study we propose a new combined approach of surgery, intralesional injection of 25 mg bevacizumab and HPV vaccine that can lead to resolution of RRP., Material and Methods: Our study involved 5 patients treated with a combination of transoral microsurgery, intralesional injection of 25 mg bevacizumab, and HPV vaccination with Gardasil 9 between April 2020 and May 2023. Standard video laryngoscopy was performed to assess the presence of papilloma and Derkay score was used to assess the severity of disease., Results: All 5 patients completed the study successfully and a complete response was achieved by all. The follow-up ranged from 8 to 45 months. The mean total Derkay score before treatment was 41 (range 25 to 52) and after the combined approach was 0 both anatomically and clinically in all patients., Conclusions: This study demonstrates the effectiveness of a combined treatment approach for RRP involving surgical intervention, intralesional injection of bevacizumab, and HPV vaccination., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Complete disinsertion of the Achilles tendon is relatively rare but is an injury of considerable clinical significance. A 50-year-old non-smoking man presented with complete disinsertion of the Achilles tendon due to an indirect low-energy trauma shortly after administration of local corticosteroid injections (LCI) for treatment of deep retrocalcaneal bursitis. Imaging studies showed complete disinsertion of the Achilles tendon as well as severe Haglund syndrome and retrocalcaneal bursitis. The tendon was repaired, and the Haglund deformity and retrocalcaneal bursa were then resected. Although Achilles tendon rupture is a frequent complication after LCI, to date, no cases of disinsertion have been published. Surgeons must be aware of this issue, especially in patients with previous insertional calcific Achilles tendinosis and Haglund syndrome. Level of Evidence V; Therapeutic Studies; Expert Opinion.

Introduction Keloids are well known for recurrence. There is no standardized regimen for the treatment of keloids. Many different treatment modalities such as surgical excision, intralesional corticosteroids, radiotherapy, and pressure earrings have been used for keloids. Surgical excision alone may result in recurrence rate of 40%-100%. This study was conducted to evaluate the efficacy of triamcinolone in preventing recurrence of Keloid. Materials and Methods Of the 40 patients who underwent excision of keloid at a tertiary care centre, surgery alone was performed in 20 patients and surgery with post operative intra-lesional triamcinolone injection was given weekly interval for 6 weeks in another 20 patients. Patients were followed up for the period of 2 years Results Recurrence was found in 5 patients who underwent excision alone and there was no recurrence among patients who received post operative intra-lesional triamcinolone. Conclusion Multi-modality treatment is better to prevent recurrence of Keloid.

Introduction: Warts or verrucae, caused by the human papillomavirus (HPV), are a benign epidermal proliferation of the skin. Most patients seek medical advice as warts are cosmetically unacceptable and can be painful. Plantar warts, in particular, are typically refractory to treatment requiring multiple treatment sessions. High recurrence rates, pain, and scarring limit the available therapeutic modalities. In contrast, immunotherapeutic approaches stimulate the host immune system by enhancing cellular immunity to eliminate the virus. Objective: To assess the safety and efficacy of intralesional vitamin D3 injection to treat multiple recurrent plantar warts. Methods: 60 patients with multiple recurrent warts were divided into two groups of 30 each. Group 1 received 0.5 ml intralesional vitamin D in the base of the largest wart, and Group 2 received 0.5 ml of normal saline. The sessions were repeated every two weeks for a maximum of four sessions, and patients were followed up for 12 months to detect any recurrences. Results: The study group showed complete clearance in 73.3% (22) individuals, while most controls (70%) showed no response. Conclusion: Intralesional vitamin D3 is a safe and effective treatment option for multiple recurrent plantar warts.

Introduction: Collagenase Clostridium histolyticum (CCH) remains the only Food and Drug Administration-approved medical treatment for Peyronie's disease (PD). The initial IMPRESS I and II trials (Investigation for Maximal Peyronie's Reduction Efficacy and Safety), which led to Food and Drug Administration approval, revealed a rate of treatment-related adverse events as high as 84%. Studies fail to provide clear definitions of complications., Objectives: To review complications, provide a CCH complication atlas, and propose management strategies for commonly encountered complications., Methods: We performed a literature review using PubMed. A photographic atlas was provided regarding complications in patients in a high-volume CCH center for PD., Results: Complications were identified and classified by nature and severity. We followed a standardized previously published grading system for hematomas. Complications include bruising, swelling, hematoma formation, back pain, and, rarely, corporal rupture. Complications were discussed, and hematomas were graded by penile surface area. Complication photographs were graded and displayed. Treatment-related adverse effects do not affect overall results., Conclusion: Recognizing and grading complications associated with CCH therapy for PD is crucial for effective patient management and informed decision making. A standardized grading system allows for consistency in reporting and comparing hematoma complication rates across studies and patient populations. Herein we provide images that will help clinicians identify and confidently manage common complications that may occur in any CCH program., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Intratumoral (IT) therapy is a powerful method of controlling tumor growth, but a major unsolved problem is the rapidity that injected drugs exit tumors, limiting on-target exposure and efficacy. We have developed a generic long acting IT delivery system in which a drug is covalently tethered to hydrogel microspheres (MS) by a cleavable linker; upon injection the conjugate forms a depot that slowly releases the drug and "bathes" the tumor for long periods. We established technology to measure tissue pharmacokinetics and studied MSs attached to SN-38, a topoisomerase 1 inhibitor. When MS ~ SN-38 was injected locally, tissues showed high levels of SN-38 with a long half-life of ~ 1 week. IT MS ~ SN-38 was ~ tenfold more efficacious as an anti-tumor agent than systemic SN-38. We also propose and provide an example that long-acting IT therapy might enable safe use of two drugs with overlapping toxicities. Here, long-acting IT MS ~ SN-38 is delivered with concurrent systemic PARP inhibitor. The tumor is exposed to both drugs whereas other tissues are exposed only to the systemic drug; synergistic anti-tumor activity supported the validity of this approach. We propose use of this approach to increase efficacy and reduce toxicities of combinations of immune checkpoint inhibitors such as αCTLA-4 and αPD-1., (© 2024. The Author(s).)

There are many therapeutic modalities for plantar warts, however treating it remains challenging. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide were observed to be effective and safe, however no comparison study between them was done. Our study was conducted to evaluate the efficacy of both therapies in the treatment of plantar warts. 90 adult patients with multiple recalcitrant plantar warts were included in our study. They were randomly allocated to one of three groups; combined digoxin and furosemide, 5-fluorouarcil, or normal saline group. Fortnightly injections were done into all studied warts till complete clearance or up to 5 sessions. Warts were evaluated clinically and dermoscopically. Clinical response was reported in 24 patients (80%) of the combined digoxin and furosemide group with 40% complete response and in 24 patients (80%) of the 5-fluorouarcil group with 33.3% complete response. No statistically significant difference was observed between the two groups concerning efficacy and safety. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide are nearly equivalent in efficacy and safety for plantar wart treatment. Dermoscopy helps to take the truthful judgment about complete clearance of warts., (© 2024. The Author(s).)

Background: Keratoacanthoma (KA) is a benign neoplasm that affects mainly photodamaged skin. It is locally destructive and may rarely spread. Surgery is not always suitable and usually disfiguring. Thus, non-operative modalities represent good alternatives., Objective: To assess and compare the efficacy of intralesional methotrexate (MTX) and 5-flurouracil (5-FU) in the treatment of KA., Patients and Methods: Randomized controlled trial included 20 patients with biopsy proven KA divided into 2 equal groups; group (A) received intralesional MTX, 25 mg/ml and group (B) received intralesional 5-FU, 50 mg/ml every 2 weeks till complete clearance or for a maximum 5 sessions., Results: In the MTX group, complete clearance was observed in 7 patients (70%) compared to 8 patients (80%) in the 5- FU group with no statistically significant difference. However, the median number of injections needed to achieve complete response in the MTX group was 3 sessions versus only 2 sessions in the 5-FU group., Limitations: the small sample size due to the relatively low incidence of KAs in our population., Conclusion: Intralesional therapy is a good alternative to surgery in selected cases of KA. Both drugs showed comparable efficacy, but 5-FU may give faster results, hence increasing patient satisfaction and compliance., (© 2024. The Author(s).)

Radiation therapy (RT) is frequently used to treat cancers, including soft-tissue sarcomas. Prior studies established that the toll-like receptor 9 (TLR9) agonist cytosine-phosphate-guanine oligodeoxynucleotide (CpG) enhances the response to RT in transplanted tumors, but the mechanisms of this enhancement remain unclear. Here, we used CRISPR/Cas9 and the chemical carcinogen 3-methylcholanthrene (MCA) to generate autochthonous soft-tissue sarcomas with high tumor mutation burden. Treatment with a single fraction of 20 Gy RT and 2 doses of CpG significantly enhanced tumor response, which was abrogated by genetic or immunodepletion of CD8+ T cells. To characterize the immune response to CpG+RT, we performed bulk RNA-Seq, single-cell RNA-Seq, and mass cytometry. Sarcomas treated with 20 Gy and CpG demonstrated increased CD8 T cells expressing markers associated with activation and proliferation, such as Granzyme B, Ki-67, and IFN-γ. CpG+RT also upregulated antigen presentation pathways on myeloid cells. Furthermore, in sarcomas treated with CpG+RT, TCR clonality analysis suggests an increase in clonal T cell dominance. Collectively, these findings demonstrate that CpG+RT significantly delays tumor growth in a CD8 T cell-dependent manner. These results provide a strong rationale for clinical trials evaluating CpG or other TLR9 agonists with RT in patients with soft-tissue sarcoma.

Intralesional corticosteroid injections are a first-line treatment for keloids; yet clinical treatment results are highly variable and often suboptimal. Variation in triamcinolone acetonide (TAC) biodistribution may be an important reason for the variable effects of TAC treatment in keloids. In this exploratory study we investigated the biodistribution of TAC in keloids and normal skin using different drug delivery techniques. Fluorescent-labeled TAC suspension was administered into keloids and normal skin with a hypodermic needle and an electronic pneumatic jet injector. TAC biodistribution was represented by the fluorescent TAC volume and 3D biodistribution shape of TAC, using a 3D-Fluorescence-Imaging Cryomicrotome System. Twenty-one keloid and nine normal skin samples were analyzed. With needle injections, the mean fluorescent TAC volumes were 990 µl ± 479 in keloids and 872 µl ± 227 in normal skin. With the jet injector, the mean fluorescent TAC volumes were 401 µl ± 252 in keloids and 249 µl ± 67 in normal skin. 3D biodistribution shapes of TAC were highly variable in keloids and normal skin. In conclusion, TAC biodistribution in keloids is highly variable for both needle and jet injection. This may partly explain the variable treatment effects of intralesional TAC in keloids. Future research is needed to confirm this preliminary finding and to optimize drug delivery in keloids., (© 2024. The Author(s).)

Treating plantar warts is still a challenging problem with a long list of diverse treatment options that none of them seems to be definitive. To evaluate the effectiveness of intralesional acyclovir versus intralesional Hepatitis-B vaccine (HBV) in treatment of multiple resistant plantar warts. Forty-eight patients with resistant plantar warts completed the study with no dropouts. They were randomized into 3 groups; group(A) receiving intralesional HBV, group (B) receiving intralesional acyclovir and group (C) receiving intralesional saline as a control group over 5 biweekly sessions or until wart clearance. Clinical outcome was assessed through sequential digital lesion photographing upon each visit. Treatment related adverse reactions were recorded. 43.8%, 37.5% & 18.7% of Groups A, B &C respectively showed a complete response. pain was obvious in 100% and 56.3% of cases receiving intralesional acyclovir and HBV respectively. Up to the 6 month follow up period, none of the complete responders in all groups returned with a recurrence. Both acyclovir and HBV showed comparable efficacy and seem to be promising options for treating plantar warts being safe, affordable, and theoretically safe in immunocompromised cases., (© 2024. The Author(s).)

Background: Head and neck squamous cell carcinoma (HNSCC) presents an ideal scenario for intratumoral therapies (IT), due to its local recurrence pattern and frequent superficial extension. IT therapies aim to effect tumor regression by directly injecting antineoplastic agents into lesions. However, there is a lack of updated evidence regarding IT therapies in HNSCC., Patients and Methods: A systematic literature search (CRD42023462291) was conducted using WebOfScience, ClinicalTrials.gov, and conference abstracts from ESMO and ASCO, identifying for IT clinical trials in patients with HNSCC, from database creation to September 12th, 2023. Efficacy as well as safety (grade ≥ 3 treatment-related adverse events[trAEs]) were reported., Results: After evaluation of 1180 articles identified by the systematic search, 31 studies treating 948 patients were included. IT injectables were categorized as chemotherapies with or without electroporation (k = 4, N = 268), oncolytic viruses, plasmids, and bacteria-based (k = 16, N = 446), immunotherapies and EGFR-based therapies (k = 5, N = 160), radioenhancer particles (k = 2, N = 68), and calcium electroporation (k = 1, n = 6). EGFR-antisense plasmids, NBTXR3 radioenhancer and immune innate agonists show best overall response rates, at 83 %, 81 % and 44 % respectively. Eleven (35 %) studies added systemic therapy or radiotherapy to the IT injections. No study used predictive biomarkers to guide patient selection. 97 % studies were phase I-II. Safety-wise, electroporation and epinephrine-based injectable trials had significant local symptoms such as necrosis, fistula formation and post-injection dysphagia. Treatment-related tumor haemorrhages of various grades were described in several trials. Grade ≥ 3 trAEs attributable to the other therapies mainly comprised general symptoms such as fatigue. There were 3 injectable-related deaths across the systematic review., Conclusion: This is the first review to summarize all available evidence of IT in HNSCC. As of today, IT therapies lack sufficient evidence to recommend their use in clinical practice. Continuing research on potential molecules, patient selection, safe administration of injections and controlled randomized trials are needed to assess their added benefit., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PJL: research funding from Roche, Merck; speakerś bureau from MSD Merck Sharp & Dohme, travel and accommodation expenses from MSD, and Novartis; and stockholding from Elli Lilly outside the current work. AHC: travel and accommodation expenses from Merck Serono and Kyowa Kirin International and research grant from Gilead (Inst) outside the current work. IB received personal fees from Merck sharp & Dohme, Sanofi, Achilles Therapeutics, eTheRNA Immunotherapies, Cancer Expert Now, Boehringer Ingelheim as a Speakers’ Bureau: Bristol Myers Squibb, Merck Serono, Roche, MSD. Lastly, as a research Funding: AstraZeneca (Inst), Bristol Myers Squibb (Inst), Celgene (Inst), Gliknik (Inst), GlaxoSmithKline (Inst), Janssen Oncology (Inst), Kura Oncology (Inst), Merck Sharp & Dohme (Inst), Novartis (Inst), Pfizer (Inst), Roche (Inst), Shattuck labs (Inst), Nanobiotix (Inst), Seattle Genetics (Inst), Immutep (Inst), Debiopharm Group (Inst), Regeneron (Inst), Boehringer Ingelheim (Inst), ISA Pharmaceuticals (Inst), Merck Serono (Inst), Seattle Genetics (Inst), Northern Biologics (Inst), VCN Biosciences (Inst), and for travel, accommodations and expenses: MSD Oncology. VM: Consulting or Advisory Role: Roche (Inst), Bayer (Inst), Pieris (Inst), BMS (Inst), Janssen (Inst), Basilea (Inst), Regeneron/Sanofi (Inst), BMS (Inst), Bayer (Inst), Nanobiotix (Inst). Research Funding: AbbVie (Inst), Achilles (Inst), AbbVie (Inst), AceaBio (Inst), Adaptimmune (Inst), ADC Therapeutics (Inst), Arcus (Inst), Ascendis Pharma (Inst), Aduro (Inst), Agenus (Inst), Amcure (Inst), Amgen (Inst), Astellas (Inst), AstraZeneca (Inst), Bayer (Inst), Beigene (Inst), Biomea (Inst), BioInvent International AB (Inst), BMS (Inst), Boehringer (Inst), Boston Therapeutics (Inst), Celgene (Inst), Daiichi Sankyo (Inst), Debiopharm (Inst), Eisai (Inst), e-Terapeutics (Inst), Exelixis (Inst), Forma Therapeutics (Inst), Genmab (Inst), GSK (Inst), Harpoon (Inst), Hutchison (Inst), Immutep (Inst), Incyte (Inst), Inovio (Inst), Iovance (Inst), Janssen (Inst), Kyowa Kirin (Inst), Lilly (Inst), Loxo (Inst), Monta Bioscience (Inst), MedSir (Inst), Menarini (Inst), Merck (Inst), Merus (Inst), Millennium (Inst), MSD (Inst), Nanobiotix (Inst), Nektar (Inst), Novartis (Inst), Odonate Therapeutics (Inst), Pfizer (Inst), Pharma Mar (Inst), PharmaMar (Inst), Principia (Inst), PsiOxus (Inst), Puma (Inst), Regeneron (Inst), Relay Therapeutics (Inst), Revolution Medicines (Inst), Rigontec (Inst), Roche (Inst), Sanofi (Inst), Sierra Oncology (Inst), Synthon (Inst), Taiho (Inst), Takeda (Inst), Tesaro (Inst), Transgene (Inst), Turning Point Therapeutics (Inst), Upsher-Smith (Inst). BD: Principal Investigator – Institutional Funding: AbbVie, Achilles, AbbVie, AceaBio, Adaptimmune, ADC Therapeutics, Arcus, Ascendis Pharma, Aduro, Agenus, Amcure, Amgen, Astellas, AstraZeneca Bayer, Beigene, Biomea, BioInvent International AB, BMS, Boheringer, Boston Therapeutics, Celgene, Daichii Sankyo, Debiopharm, Eisai, e-Terapeutics, Exelisis, Forma Therapeutics, Genmab, GSK, Harpoon, Hutchison, Immutep, Incyte, Inovio, Iovance, Janssen, Kyowa Kirin, Lilly, Loxo, Monta Bioscience, MedSir, Menarini, Merck, Merus, Millennium, MSD, Nanobiotix, Nektar, Novartis, Odonate Therapeutics, Pfizer, Pharma Mar, PharmaMar, Principia, PsiOxus, Puma, Regeneron, Relay Therapeutics, Revolution Medicines, Rigontec, Roche, Sanofi, Sierra Oncology, Synthon, Taiho, Takeda, Tesaro, Transgene, Turning Point Therapeutics, Upshersmith. KJH received honoraria from Arch Oncology (Inst), AstraZeneca (Inst), BMS (Inst), Boehringer Ingelheim (Inst), Merck Serono (Inst), MSD (Inst), Oncolys Biopharma (Inst), Pfizer (Inst), Replimune (Inst), Inzen Therapeutics (Inst) and Codiak Biosciences (Inst). Consulting or Advisory Role: Arch Oncology (Inst), AstraZeneca (Inst), BMS (Inst), Boehringer Ingelheim (Inst), Merck Serono (Inst), MSD (Inst), Oncolys BioPharma (Inst), Replimune (Inst), Inzen Therapeutics (Inst) Speakers’ Bureau: BMS (Inst), Merck Serono (Inst), MSD (Inst) Research Funding: AstraZeneca (Inst), Merck Sharp & Dohme (Inst), Replimune (Inst), Boehringer Ingelheim (Inst). All other authors have declared no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: An international multidisciplinary panel of experts aimed to provide consensus guidelines describing the optimal intratumoral and intranodal injection of NBTXR3 hafnium oxide nanoparticles in head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, and cervical lymph nodes and to review data concerning safety, feasibility, and procedural aspects of administration., Methods: The Delphi method was used to determine consensus. A 4-member steering committee and a 10-member monitoring committee wrote and revised the guidelines, divided into eight sections. An independent 3-member reading committee reviewed the recommendations., Results: After two rounds of voting, strong consensus was obtained on all recommendations. Intratumoral and intranodal injection was deemed feasible. NBTXR3 volume calculation, choice of patients, preparation and injection procedure, potential side effects, post injection, and post treatment follow-up were described in detail., Conclusions: Best practices for the injection of NBTXR3 were defined, thus enabling international standardization of intratumoral nanoparticle injection., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: Keloids and hypertrophic scars cause physical and psychosocial problems. A combination of 5-fluorouracil (5-FU) and triamcinolone acetonide (TAC) may enhance the treatment of pathologic scars, although the evidence base is limited. The authors compared the efficacy and complication rates of combination intralesional TAC and 5-FU with those of monotherapy intralesional TAC or 5-FU for the treatment of keloids and hypertrophic scars., Methods: Embase, MEDLINE, and CENTRAL were searched by two independent reviewers. The primary outcome was treatment efficacy (51% to 100% improvement). Study quality and risk of bias were assessed using the Cochrane risk of bias tool., Results: Of 277 articles screened, 13 studies were included, comprising 12 randomized control trials and one nonrandomized study. Six studies compared combination intralesional therapy versus monotherapy 5-FU, and nine studies compared combination intralesional therapy versus monotherapy TAC. The combined group demonstrated superior objective treatment efficacy compared with the monotherapy TAC group (OR, 3.45; 95% CI, 2.22 to 5.35; I 2 = 0%; P < 0.00001) and monotherapy 5-FU group (OR, 4.17; 95% CI, 2.21 to 7.87; I 2 = 0%; P < 0.0001). Telangiectasia was less frequent in combination therapy (OR, 0.24; 95% CI, 0.11 to 0.52; I 2 = 0%; P = 0.0003) compared with monotherapy TAC., Conclusions: Combined intralesional TAC and 5-FU administration demonstrated superior treatment efficacy outcomes compared with monotherapy TAC or 5-FU. Patient-reported outcome measures should be incorporated in the design of future research to justify clinical recommendations., Clinical Relevance Statement: Combined TAC and 5-FU has demonstrated superior treatment efficacy outcomes compared to monotherapy TAC or 5-FU in the treatment of hypertrophic scars and keloids., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background: Dupuytren disease (DD) is one of the most common disorders of the hand, affecting 5.7% to 11.7% of the global population. This study seeks to evaluate the 10-year efficacy of the 2 most prominent treatment modalities for DD in Veterans Affairs hospitals, injectable collagenase Clostridium histolyticum versus open fasciectomy., Methods: A retrospective review was conducted of all electronic medical records of patients who underwent open fasciectomy or collagenase injection to treat their persistent Dupuytren contracture between April 2011 and April 2021. All procedures were performed by 1 of 5 senior surgeons at the same Veterans Affairs Hospital., Results: A total of 232 patients were treated for DD, with 247 collagenase injections and 44 open fasciectomies performed in this sample. Collagenase patients were, on average, 6.51 years after intervention at the time of review. Open fasciectomy patients were, on average, 4.56 years after operation at the time of review. Collagenase decreased contractures, on average, by 29.40 degrees, whereas open fasciectomy decreased contractures, on average, by 38.59 degrees. Of the contractures that were initially classified as resolved, 50 of 155 (32.2%) treated with collagenase and 6 of 56 (10.7%) treated with open fasciectomy recurred. The use of open fasciectomy compared with collagenase injections to treat contracture was associated with a 74.2% decrease in the likelihood of recurrence., Conclusions: This study found that treatment of DD with collagenase injection is associated with a significantly lower degree of deformity correction, lower rate of resolution, and increased rate of recurrence when compared with open fasciectomy., Competing Interests: Conflicts of interest and sources of funding: The authors declare that they have no conflict of interest and received no funding to conduct this study. Because this is a retrospective review, this article does not contain any studies with human or animal subjects., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Plantar warts are common skin lesions that continue to represent a therapeutic challenge. They are still resistant to therapy and are highly recurrent, despite the diverse number of treatments available. Therapies targeting vasculature, such as pulsed dye laser, have been used successfully in the treatment of plantar warts. Polidocanol, a detergent sclerosant approved for the sclerotherapy of incompetent and dilated saphenous veins, has also been used as an off-label therapy for a wide range of skin conditions with vascular components such as hemangiomas and pyogenic granuloma. The current, open-label, prospective, pilot study aimed to evaluate the safety and efficacy of the intralesional polidocanol 3% in the treatment of plantar warts. Twenty patients (11 females and 9 males), with plantar warts, aged 12-50 years received biweekly sessions of intralesional polidocanol 3% until complete clearance or for a maximum of 6 sessions. Response to treatment was graded as complete (100% clearance), partial (50-99%), and no response (< 50%). At the end of the study, 12 (60%) patients achieved complete clearance of their warts after 1-5 sessions, 5 (25%) patients had only partial response, and 3 (15%) patients did not achieve any clearance of their warts. The procedure was largely tolerable by patients. Pain at the injection site and bruises were reported by 9 (45%) and 2 (10%) patients, respectively. Both side effects resolved spontaneously and completely within a few days. The findings of the current study suggest that intralesional injection of 3% polidocanol in biweekly sessions may be a safe, effective, and tolerable method for the treatment of plantar warts., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Mucosal melanoma, an aggressive type of malignancy different from the cutaneous melanomas commonly seen in the head and neck region, represents < 1% of all malignant melanomas. The pathogenesis of mucosal melanoma is unknown. Targetable mutations commonly seen in cutaneous melanoma, such as in the BRAF and NRAS genes, have a lower incidence in mucosal melanoma. Mucosal melanoma carries a distinct mutational pattern from cutaneous melanoma. Surgery with negative margins is the first-line treatment for mucosal melanoma, and systemic therapy is not well defined. Talimogene laherparepvec, an oncolytic viral immunotherapy, is United States Food and Drug Administration approved for the treatment of advanced malignant cutaneous melanoma, with local therapeutic benefits. Mucosal melanoma was initially excluded from talimogene laherparepvec's initial phase III clinical trial., Case Presentation: We present the case of a white female patient in her 40s with past medical history of systemic lupus erythematous, scleroderma, and estrogen-receptor-positive invasive ductal breast carcinoma. Following a bilateral mastectomy, the patient was found to have BRAF-negative mucosal melanoma of her hard palate with a soft palate skip lesion. Owing to the presence of a skip mucosal lesion as well as the anticipated defect and need for free-flap reconstructive surgery, nonsurgical management was considered. The patient was referred to medical oncology, where-based on the patient's complicated medical history and the risk of immunotherapy possibly worsening her prior autoimmune diseases-local talimogene laherparepvec injections were chosen as the primary therapy for her mucosal lesions. Though talimogene laherparepvec is approved for the treatment of cutaneous melanoma, there are limited data available on the use of talimogene laherparepvec in mucosal melanomas., Conclusion: The patient had a complete local tumor response at both the primary lesion as well as the skip lesion with the local injections. She had no side effects and maintained a high quality of life during treatment., (© 2024. The Author(s).)

Background: Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older., Objective: The objective of this study was to provide evidence-based recommendations for the management of acne., Methods: A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations., Results: This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements., Limitations: Analysis is based on the best available evidence at the time of the systematic review., Conclusions: These guidelines provide evidence-based recommendations for the management of acne vulgaris., Competing Interests: Conflicts of interest Rachel V.S. Reynolds, MD, Carol E. Cheng, MD, Kelly Druby, Megha M. Tollefson, MD, and Jung Min Han, PharmD, MS, have no relationships to disclose. Howa Yeung, MD, MS, serves as an investigator for American Acne & Rosacea Society, Department of Veterans Affairs, and National Institutes of Health receiving grants and research funding; as an independent contractor for American Academy of Dermatology and Journal of the American Medical Association receiving fees; as a speaker/faculty educator for Dermatology Digest receiving honoraria. Fran Cook-Bolden, MD, serves as an advisory board member for AbbVie, Dermavant Sciences, Inc., Galderma Global, Novartis, Ortho Dermatologics, and Pfizer Inc. receiving honoraria; as an investigator for Arcutis Biotherapeutics receiving grant and research funding; as a speaker for Galderma Laboratories, LP, Journey Medical Corporation, and Ortho Dermatologics receiving honoraria; as others for Topix Pharmaceuticals, Inc. receiving other financial benefit. Seemal R. Desai, MD, serves an advisory board member for Foundation for Research & Education of Dermatology receiving fees; as a consultant for AbbVie, Allergan, Inc, Almirall, Amgen, Apogee, Avita, Ballature Beauty, Beiersdorf, Inc., Bristol-Myers Squibb, Candela Corporation, Cassiopea S.p.A., Castle Biosciences, Cutera, Inc., Dermavant Sciences, Dermira, Eli Lilly and Company, EPI Health, Ferndale Laboratories, Inc., Foamix, Galderma Laboratories, LP, Gore Range Capital, Hyphens Pharma, Incyte Corporation, Janssen Pharmaceuticals, Inc, Johnson and Johnson, Leo Pharma Inc., L'Oreal USA Inc., Lyceum Health, Ortho Dermatologics, Pfizer Inc., Revision Skincare, Sanofi/Regeneron, Scientis, Skin Science Advisors, UCB, Verrica Pharmaceuticals Inc., and VYNE Therapeutics receiving fees, honoraria, and/or stock options; as an investigator for AOBiome, LLC, Atacama Therapeutics, Dermavant Sciences, Incyte Corporation, and SkinMedica, Inc. receiving grants and research funding; as a speaker for AbbVie, Dermira, Galderma Laboratories, LP., and Pfizer Inc. receiving fees; as a stockholder for Gore Range Capital; as other role for Medscape receiving fees. Esther E. Freeman, MD, PhD, serves as an investigator for International League of Dermatologic Societies and National Institutes of Health receiving grants and research funding; as an author for UptoDate, Inc. and British Journal of Dermatology, receiving honoraria or salary; as a speaker for Harvard University. Jonette E. Keri, MD, PhD, serves as an advisory board member for Ortho Dermatologics receiving honoraria; as a consultant for Almirall receiving fees; as an investigator for Galderma USA receiving grants and research funding; as a speaker for Foamix Pharmaceuticals Ltd and VYNE Therapeutics receiving honoraria. Linda F. Stein Gold, MD, serves as an advisory board member for AbbVie, Almirall, Aqua, Dermavant Sciences, Foamix, Galderma Laboratories, L.P., GlaxoSmithKline, Incyte Corporation, La Roche-Posay Laboratorie Pharmaceutique, LEO Pharma, US, Lilly ICOS LLC, Merz Pharmaceuticals, LLC, Pfizer Inc., Promius Pharmaceuticals, Sanofi/Regeneron, Taro Pharm, and Valeant Pharmaceuticals International receiving honoraria; as a consultant for AnaptysBio, BMS, Botanix Pharmaceuticals, Cutera, Inc., Incyte Corporation, Janssen Scientific Affairs, LLC, Sol-Gel Technologies, Taro Pharm, The Acne Store, and UCB receiving honoraria or grants and research funding; as an investigator for AbbVie, Allergan, Inc., AnaptysBio, Galderma Laboratories, L.P., Leo Pharma Inc., Novartis Pharmaceuticals Corp., Pfizer Inc., Topica, and Valeant Pharmaceuticals International receiving grants and research funding; as a speaker for Actavis, Almirall, BMS, Dermira, Pfizer Inc., Sanofi/Regeneron, Sun Pharmaceutical Industries Ltd., and VYNE Therapeutics receiving honoraria. Jerry K. L. Tan, MD, serves as an advisory board member for Abbott Laboratories, Cutera, Inc., Galderma Laboratories, L.P, and Sun Pharmaceutical Industries Ltd receiving honoraria or grants and research funding; as a consultant for Bausch Health, Boots, Galderma Research & Development, LLC, and Loreal Research and Innovation receiving honoraria; as an independent contractor for Norvatis receiving fees; as an investigator for Allergan, AnaptysBio, Cutera, Inc., Eli Lilly and Co., Galderma Laboratories, L.P, Lilly ICOS LLC, Pfizer, and UCB for receiving grants and research funding; as a speaker for Bausch Health, LEO Laboratories Ltd (LEO Pharma), and Vichy Laboratories receiving honoraria. Jonathan S. Weiss, MD, serves as an advisory board member for Bristol-Myers Squibb, Dermavant Sciences, Foamix, Galderma Laboratories, L.P., Incyte Corporation, Novartis, and UCB receiving honoraria; as a consultant for Arcutis, Inc., Biofrontera, Cutera, Inc., Leo Pharma Inc, Ortho Dermatologics, and UCB receiving fees or honoraria; as an investigator for AbbVie, Bausch Health, Biofrontera, Bristol-Myers Squibb, Cutera, Inc., Dermavant Sciences, Foamix, Galderma Laboratories, L.P., LEO Pharma, Mindera, Moberg Pharma North, America LLC, Novartis, Palvella Therapeutics, and Verrica Pharmaceuticals Inc receiving grants and research funding; as a speaker for AbbVie, Arcutis, Inc., Galderma Laboratories, L.P., Ortho Dermatologics, Regeneron, and Sanofi Genzyme receiving honoraria. Peggy A. Wu, MD, serves as others for UptoDate, Inc. receiving honoraria. Andrea L. Zaenglein, MD, serves as a consultant for Church & Dwight Co., Inc. and UCB receiving fees or honoraria; as an investigator for AbbVie, Arcutis Biotherapeutics, Biofrontera AG, Galderma Laboratories, L.P., and Incyte Corporation receiving grants and research funding. John S. Barbieri, MD, MBA serves as investigator for National Institutes of Health and National Psoriasis Foundation receiving grants and research funding., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Topical and intralesional (IL) treatments may be considered the first-line therapy in patients with hidradenitis suppurativa (HS); however, the evidence supporting their use is limited. The aim of our review is to evaluate the efficacy and safety profile of topical and IL treatments in patients with HS., Materials and Methods: We designed a systematic review of the current medical literature available following the PICO(T) method. And including all types of studies (Study type [T]) of individuals with HS of any sex, age, and ethnicity (Population [P]) who received any topical or IL treatment for HS (Intervention [I]) compared to placebo, other treatments, or no treatment at all (Comparator [C]), and reported efficacy and/or safety outcomes (Outcomes [O]). Two outcomes were defined: quality of life and the no. of patients with, at least, one adverse event. The search was conducted in the Cochrane Library, MEDLINE, and EMBASE databases; study selection was performed based on pre-defined criteria. The risk of bias was determined in each study., Results: We obtained a total of 11,363 references, 31 of which met the inclusion criteria. These studies included 1143 patients with HS, 62% of whom were women. A total of 10, 8, 6, 2, and 5 studies, respectively, evaluated the use of photodynamic therapy (PDT), glucocorticoids, resorcinol, topical antibiotics, and other interventions. Most articles were case series (n=25), with only five randomized clinical trials (RCTs) and one cohort study. RCTs showed improvement in disease activity with topical clindamycin and botulinum toxin (BTX) vs placebo, and PDT with methylene blue (MB) niosomal vs free MB; however, intralesional triamcinolone acetonide was not superior to placebo. The risk of bias was low in three RCTs and high in two RCTs., Conclusion: The quality of evidence supporting the use of topical, or IL treatments is low. However, it supports the use of topical clindamycin, PDT, and BTX. Well-designed RCTs with standardized outcomes and homogeneous populations of patients and lesions are needed to support decision-making in the routine clinical practice., (Copyright © 2023 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Peyronie's disease (PD) is a condition of penile connective tissue affecting up to 10% of men worldwide. In the complexity of its management, nonsurgical treatments, such as intraplaque injections, are gaining attention. The current literature shows data on the efficacy of intraplaque injections of hyaluronic acid (HA) mainly in acute-phase PD. However, data on injections of HA in stable-phase PD are lacking. Data for this retrospective study were derived from a prospectively maintained database of private patients presenting at a private medical practice affiliated to the University of Naples "Federico II" (Naples, Italy) with stable-phase PD between January 2020 and March 2023. Patients underwent a standard protocol of three injections, each administered at a two-week interval. During the intervals, patients performed vacuum device therapy, penile stretching, and modeling exercises. All patients compiled the Peyronie's Disease Questionnaire (PDQ) and Global Assessment of Peyronie's Disease (GAPD) at baseline and 2 weeks after the third injection. A penile Doppler ultrasound was performed 2 weeks after the last injection to record the final curvature. Overall, we recruited 62 patients with stable-phase PD and a mean (±standard deviation [s.d.]) curvature of 52.7° (±9.7°). After 6 weeks, eight (12.9%) patients did not experience any curvature improvement. The remaining 54 patients had a final mean (±s.d.) curvature of 40.3° (±9.1°) with P < 0.001, compared to that before treatment. We found improvement in all PDQ domains (all P ≤ 0.01), and 50 (80.6%) patients reported subjective improvement of the penile curvature according to the GAPD. In conclusion, we demonstrated that after three injections of HA administered according to the adopted protocol, patients with stable-phase PD could experience significant improvements in penile curvature, and physical and psychological consequences of the disease without significantly relevant side effects., (Copyright © 2024 Copyright: © The Author(s)(2024).)

Background: No single treatment is ideal for genital warts with high rate of resistance using conventional modalities as topical podophyllin; however, several intralesional immunotherapies are being tested nowadays, with variable results. In this study, we compared the safety and efficacy of treating resistant and recurrent genital warts by 2 intralesional immunotherapies [ Candida antigen and measles, mumps, and rubella (MMR) vaccine] and compared them with topical podophyllin., Patients/methods: A total of 45 patients with resistant or recurrent genital warts were enrolled in this study. Size and number of warts were detected in each patient, patients were divided into 3 groups. Group A injected with intralesional Candida antigen. Group B with intralesional MMR vaccine. Group C were treated with topical 25% podophyllin. Patients received a session every 2 weeks for 3 treatment sessions., Results: With regard to the reduction in size and number of all warts, the best response was obtained in Candida antigen group where 46.7% showed complete clearance and 40% showed partial response followed by MMR group and the last was the podophyllin group, with no significant difference between them. Complete clearance of mother warts was noticed in 86.7% of Candida group, 53.3% in MMR group, and last 40% in podophyllin group, with a significantly better response in the Candida group ( P  = .027)., Conclusion: Both intralesional Candida antigen and MMR vaccine are simple, safe, and effective treatment options with comparable results and better response than topical podophyllin., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: This study aimed to compare the effectiveness of carbon dioxide (CO 2 ) laser vaporisation versus intralesional injection of triamcinolone acetonide (TA) in the management of oral lichen planus (OLP)., Methods: A randomised clinical trial with a split-mouth design was conducted on 16 patients with bilateral symptomatic OLP lesions. One side was treated with CO 2 laser vaporisation, and the counterpart was treated with TA intralesional injection. The reticular-erythematous-ulcerative (REU) score, Thongprasom sign scoring (TSS), visual analogue scale (VAS) and lesion area were used to evaluate the lesions at weeks 0, 4 and 9. All participants were followed up for 9 months., Results: Reduction in the REU, TSS scores and lesion area from baseline to the end of treatment was significantly greater in the CO 2 group than in the TA group (p values were 0.001, 0.002 and 0.048 respectively). However, the reduction in VAS score did not differ between the two groups (p = 0.54). The recurrence rate was significantly higher in the TA group than in the CO 2 group (75% vs. 31.1%; p = 0.016)., Conclusions: CO 2 laser vaporisation was more effective than TA intralesional injection in managing OLP and decreased recurrence rates., (© 2023 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

Background: Testosterone plays an important role in collagen metabolism, transforming growth factor-β1 expression, and wound healing, which are all critical factors in pathogenesis of Peyronie's disease. Some clinical studies have suggested an association between Peyronie's disease and hypogonadism., Objective: We sought to investigate whether baseline total testosterone levels influence response to intralesional collagenase clostridium histolyticum in Peyronie's disease., Methods: A retrospective review of patients receiving collagenase clostridium histolyticum injections with available total testosterone levels within 1 year of initial injection was conducted at a single institution. Baseline demographics, hypogonadal status, total testosterone, number of collagenase clostridium histolyticum cycles, and pre- and post-treatment degrees of curvature were collected. Hypogonadism was defined as total testosterone <300 ng/dL., Results and Discussion: Thirty-six men were included with mean age of 58.2 years (SD 10.4) and mean body mass index 26.8 (SD 3.2). The mean total testosterone was 459.2 ng/dL (SD 144.0), and four (11.1%) were hypogonadal. Mean pre-treatment curvature was 47.6°, and mean post-treatment curvature was 27.8°, with mean improvement of 19.9° (40.1%). Hypogonadal status was not significantly associated with more severe curvature, 46.4° among hypogonadal men as to 57.5° among eugonadal men (p = 0.32). On linear regression analysis, total testosterone did not significantly predict improvement in degrees (β = -0.02; R 2  = 0.06; p = 0.14) or percent (β = 0.0; R 2  = 0.05; p = 0.18). Improvement in neither degrees nor percent differed significantly by hypogonadal status (p = 0.41 and 0.82, respectively). The cycle number did significantly predict greater improvement in curvature on both univariate and multivariate analyses (β = 5.7; R 2  = 0.34; p < 0.01)., Conclusion: Neither total testosterone nor hypogonadism is associated with a degree of improvement after collagenase clostridium histolyticum treatment., (© 2023 American Society of Andrology and European Academy of Andrology.)

The formation of penile keloid after circumcision is an uncommon complication. Herein, we report two pediatric cases of large circumferential keloids that developed post-circumcision and were successfully treated by surgical excision and intralesional triamcinolone injections. In addition, we provide a comprehensive review of the reported cases of penile keloids that developed after circumcision in the literature to highlight the various presentations, treatment options, and outcomes for this condition., (© 2023 Wiley Periodicals LLC.)

Background: Mesotherapy is a popular cosmetic procedure for localized delivery of substances. However, due to the lack of standardized processes, there are potential risks of adverse reactions. Granulomas formation is one of the chronic reactions which impose significant physical and mental burdens on patients., Objectives: The aim of this analysis is to evaluate the safety and feasibility of combining intense pulsed light (IPL) with intralesional corticosteroids for treating noninfectious granulomas after mesotherapy., Methods: This retrospective observational case series included patients who suffer from noninfectious granulomas after mesotherapy and received combination of IPL and intralesional corticosteroids treatment between October 2021 and December 2022 at Peking University Shenzhen Hospital, Shenzhen, China. The process and effect were analyzed and summarized., Results: Among the seven patients, five expressed extreme satisfaction with the efficacy, while two was slightly satisfied. The physicians believed that all patients had shown significant improvement. No adverse reactions or recurrences were observed during follow-up., Conclusion: Based on this analysis, the application of the combined treatment in patients suffering from noninfectious granuloma due to mesotherapy demonstrates good clinical efficacy and safety, making it worth considering as a treatment option., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Objective: To present the functional results obtained and the possible surgical difficulties after the surgical treatment of Dupuytren's disease (DD) recurrence in patients previously treated with Clostridium histolyticum (CCH) collagenase., Materials and Methods: In this prospective study, 178 patients with DD were treated with CCH from 2011 to 2018; During long-term postoperative follow-up, 34 patients (19.1%) had recurrence of DD. In all patients injected in the IFP the disease recurred; In patients injected in the MCP, recurrence was highest in grade III and IV of the Tubiana classification, with involvement of the 5th finger and the two-finger Y-chord. Fourteen patients (7,8%) required surgery by partial selective fasciectomy due to recurrence of cord DD infiltration. The clinical and functional results of the patients, the difficulty of the surgical technique and the anatomopathological analysis of the infiltrated cords were evaluated in comparison with those of cords and patients who had had no previous CCH treatment., Results: In all patients, cord rupture was achieved after injection, reducing joint contracture. In 14 patients, we observed during the follow-up the existence of DD recurrence that required surgical treatment by selective partial fasciectomy. There were no major difficulties in surgery and good clinical and functional results at 6 months of follow-up. The anatomopathological study of the resected tissue did not present histological alterations with respect to the samples obtained from patients initially treated by selective partial fasciectomy., Conclusions: Selective fasciectomy after CCH injection does not lead to important operative difficulties, as long as the CCH injection is performed according to the recommendations. There were no histological changes in the tissue after CCH injection., Level of Evidence: III., (© 2024. The Author(s).)

Israel is endemic for Old-World cutaneous leishmaniasis. The most common species is Leishmania major. However, the available treatment options are limited. This study's objective was to compare the authors' experience with different antimony intralesional treatments of Leishmania major cutaneous leishmaniasis. A retrospective evaluation was undertaken for cases of Leishmania major cutaneous leishmaniasis treated by pentavalent antimony in a university-affiliated medical centre in Israel. The previous treatment of intralesional sodium stibogluconate (Pentostam®) was compared with the current treatment of meglumine antimoniate (Glucantime®). One hundred cases of cutaneous leishmaniasis were treated during the study period, of whom 33 were treated with intralesional sodium stibogluconate and 67 were treated with intralesional meglumine antimoniate. The patients were 78 males and 22 females, mean age 24 (range 10-67) and there was a total of 354 skin lesions. Within 3 months from treatment, 91% (30/33) of the intralesional sodium stibogluconate group and 88% (59/67) of the intralesional meglumine antimoniate group had complete healing of the cutaneous lesions after an average of 3 treatment cycles (non-statistically significant). In conclusion, the 2 different medications have the same efficacy and safety for treating cutaneous leishmaniasis. Pentavalent antimoniate intralesional infiltration treatment is safe, effective, and well tolerated with minimal side effects for Old-World cutaneous leishmaniasis.

Immune checkpoint inhibitors (ICIs) offer new options for the treatment of patients with solid cancers worldwide. The majority of colorectal cancers (CRC) are proficient in mismatch-repair (pMMR) genes, harboring fewer tumor antigens and are insensitive to ICIs. These tumors are often found to be immune-deserted. We hypothesized that forcing immune cell infiltration into the tumor microenvironment followed by immune ignition by PD1 blockade may initiate a positive immune cycle that can boost antitumor immunity. Bioinformatics using a public database suggested that IFNγ was a key indicator of immune status and prognosis in CRC. Intratumoral administration of IFNγ increased immune cells infiltration into the tumor, but induced PD-L1 expression. A combined treatment strategy using IFNγ and anti-PD-1 antibody significantly increased T cell killing of tumor cells in vitro and showed synergistic inhibition of tumor growth in a mouse model of CRC. CyTOF found drastic changes in the immune microenvironment upon combined immunotherapy. Treatment with IFNγ and anti-PD1 antibody in CT26 tumors significantly increased infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). IFNγ had a more pronounced effect in decreasing intratumoral M2-like macrophages, while PD1 blockade increased the population of CD8+Ly6C + T cells in the tumor microenvironment, creating a more pro-inflammatory microenvironment. Additionally, PD1 induced increased expression of lymphocyte activating 3 (LAG3) in a significant fraction of CD8 + T cells and Treg cells, indicating potential drug resistance and feedback mechanisms. In conclusion, our work provides preclinical data for the Combined immunotherapy of CRC using intratumoral delivery of IFNγ and systemic anti-PD1 monoclonoal antibody., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Lymphocytic choriomeningitis virus (LCMV) belongs to the Arenavirus family known for inducing strong cytotoxic T-cell responses in both mice and humans. LCMV has been engineered for the development of cancer immunotherapies, currently undergoing evaluation in phase I/II clinical trials. Initial findings have demonstrated safety and an exceptional ability to activate and expand tumor-specific T lymphocytes. Combination strategies to maximize the antitumor effectiveness of LCMV-based immunotherapies are being explored., Methods: We assessed the antitumor therapeutic effects of intratumoral administration of polyinosinic:polycytidylic acid (poly(I:C)) and systemic vaccination using an LCMV-vector expressing non-oncogenic versions of the E6 and E7 antigens of human papillomavirus 16 (artLCMV-E7E6) in a bilateral model engrafting TC-1/A9 cells. This cell line, derived from the parental TC-1, exhibits low MHC class I expression and is highly immune-resistant. The mechanisms underlying the combination's efficacy were investigated through bulk RNA-seq, flow cytometry analyses of the tumor microenvironment, selective depletions using antibodies and clodronate liposomes, Batf3 deficient mice, and in vivo bioluminescence experiments. Finally, we assessed the antitumor effectiveness of the combination of artLCMV-E7E6 with BO-112, a GMP-grade poly(I:C) formulated in polyethyleneimine, currently under evaluation in clinical trials., Results: Intratumoral injection of poly(I:C) enhanced the antitumor efficacy of artLCMV-E7E6 in both injected and non-injected tumor lesions. The combined treatment resulted in a significant delay in tumor growth and often complete eradication of several tumor lesions, leading to significantly improved survival compared with monotherapies. While intratumoral administration of poly(I:C) did not impact LCMV vector biodistribution or transgene expression, it significantly modified leucocyte infiltrates within the tumor microenvironment and amplified systemic efficacy through proinflammatory cytokines/chemokines such as CCL3, CCL5, CXCL10, TNF, IFNα, and IL12p70. Upregulation of MHC on tumor cells and a reconfiguration of the gene expression programs related to tumor vasculature, leucocyte migration, and the activation profile of tumor-infiltrating CD8 + T lymphocytes were observed. Indeed, the antitumor effect relied on the functions of CD8 + T lymphocytes and macrophages. The synergistic efficacy of the combination was further confirmed when BO-112 was included., Conclusion: Intratumoral injection of poly(I:C) sensitizes MHC low tumors to the antitumor effects of artLCMV-E7E6, resulting in a potent therapeutic synergy., Competing Interests: Competing interests: PB received research funding from Hookipa Pharma. IM reports receiving commercial research grants from AstraZeneca, BMS, Highlight Therapeutics, Alligator, Pfizer Genmab and Roche; has received speakers bureau honoraria from MSD; and is a consultant or advisory board member for BMS, Roche, AstraZeneca, Genmab, Pharmamar, F-Star, Bioncotech, Bayer, Numab, Pieris, Gossamer, Alligator and Merck Serono. MA declares receiving a commercial research grant from Highlight Therapeutics. TS, KKO, and HL are employees of Hookipa Pharma. MQ is an employee of Highlight Therapeutics. The rest of the authors have no conflict of interest to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Xiaflex® (collagenase clostridium histolyticum) is a Food and Drug Administration-approved treatment for patients with Peyronie's disease. Despite its approval and implementation, there is concern that urologists in training are offered minimal exposure to its use. Thus, the purpose of this study was to evaluate the exposure of urology residents to Peyronie's disease and its management, particularly Xiaflex®. A Google Forms survey regarding the exposure of residents to Peyronie's disease and use of Xiaflex® was created and disseminated through email to urology programs. Overall, 47 institutional responses were received. At 45 institutions (95.7%), residents receive training in directly evaluating and caring for patients with Peyronie's disease. At 46 institutions (97.9%), residents receive training in observing and/or performing surgical procedures for Peyronie's disease. Residents at 31 institutions (66.0%) receive observational or procedural training for non-surgical management of Peyronie's disease, specifically Xiaflex®. Residents receive non-surgical training from an academic faculty who is fellowship trained in sexual medicine at 25 institutions and an academic faculty not trained in sexual medicine at six institutions. There exists a glaring disparity in residency exposure to Xiaflex®. Further research is warranted to elucidate how programs can provide residents with further exposure to the use of Xiaflex® in patients with Peyronie's disease., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Collagenase clostridium histolyticum (collagenase) was introduced in 2010 creating a nonoperative treatment option for Dupuytren disease with promising results in sponsored clinical trials. A meta-analysis was performed to investigate industry sponsorship bias., Methods: A systematic review of collagenase treatment of Dupuytren contracture was conducted. Articles containing mesh terms including "microbial collagenase" and "Dupuytren's contracture" were searched and limited to only clinical trials with similar protocols for inclusion. Meta-analysis of treatment endpoints of correction of contracture to 0-5 degrees after first and last injection was conducted comparing sponsored versus nonsponsored studies., Results: Sixteen of the 29 identified articles met criteria for inclusion. Nonsponsored studies reported a significantly higher rate of meeting the primary treatment endpoint compared to sponsored studies after single injection for all joints (69.6% vs 56% P < 0.01), metacarpophalangeal joint (96% vs 64% P < 0.01), and proximal interphalangeal joint (67% vs 36% P = 0.011). The correction in contracture rates was similar between groups with studies evaluating more than one injection., Conclusions: Nonsponsored studies published higher success rates in meeting the primary endpoint of full correction after single injection than sponsored studies; however, similar results with multiple injections. This study demonstrated that sponsored studies of collagenase produced highly powered studies that may be reliably depended on for evidence-based clinical application., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Peyronie's disease continues to be poorly understood. We characterize the presenting features of Peyronie's disease within a large cohort and elucidate the factors that correlate with surgical intervention. Univariate and multivariate analyses were performed on 1483 consecutive patients to assess pre-operative predictors of surgical intervention for Peyronie's disease. Overall, 1263 patients met inclusion criteria. Mean age was 55.4 ± 11.1 years with a mean duration of disease at presentation of 33.2 ± 42.5 months. Mean primary curvature was 49.8 ± 20.8°. Primary ventral curvature was present in 11.4% and 36.5% of patient had a multiplanar curvature. During penile duplex ultrasound evaluation indentation/narrowing deformities were appreciated in 76.0%, hourglass deformity in 10.1%, and hinge effect in 33.0% of patients. Calcification was seen in 30.1% of patients. Operative intervention occurred in 35.3% of patients. Degree of primary curvature (1.03 OR, p < 0.001), hourglass deformity (1.82 OR, p = 0.01), decreased tunical elasticity (1.20 OR, p = 0.03), and prior intralesional collagenase clostridium histolyticum injections (2.94 OR, p < 0.001) predicted surgical correction on multivariate analysis. Compared to historical studies, we found a higher incidence of severe degree of curvature (27.5% >60°), indentation deformities, hinge-effect, multiplanar curvature and penile calcifications. Ultimately, predictors of surgical intervention included those with worse erectile function and more severe characteristics., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The objective of this study is to evaluate the safety and feasibility of the combined simultaneous percutaneous needle tunneling coupled with injection of platelet-rich plasma in the outpatient department for the treatment of Peyronie's disease. This prospective, non-randomized, cohort and preliminary study included patients who underwent this procedure from November 2020 to July 2022. The main outcome was an improvement in penile curvature. Fifty-four patients were enrolled and underwent 6 sessions under local anesthesia followed by vacuum therapy for the treatment of Peyronie's disease in our outpatient unit. The amendment of the curvature angle was significant with a median correction percentage of -44.40% interquartile range (-66.70 to (-39.70)), [p-value = 0.001, 95% CI (-29.76 to (-18.02)), paired Student's t-test]. The median pre-treatment curvature angle was 45° (40-75), and the median post-treatment was 30° (20-40). The median score for pain during the procedure was 3 (0-4.25) according to a 10-point visual analogic scale. After two hours, 20.37% of patients still had pain but none required any pain medication. 50% of patients had a minor hematoma and 75.93% patients reported penile ecchymosis. A single patient reported an injection site skin infection. In our experience percutaneous needle tunneling with platelet-rich plasma injections for Peyronie's disease in the outpatient setting is a safe, effective, and feasible treatment of penile deformity for PD., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Worldwide, breast cancer is the most important cancer in incidence and prevalence in women. Different risk factors interact to increase the probability of developing it. Biological agents such as helminth parasites, particularly their excretory/secretory antigens, may play a significant role in tumor development. Helminths and their antigens have been recognized as inducers or promoters of cancer due to their ability to regulate the host's immune response. Previously in our laboratory, we demonstrated that chronic infection by Toxocara canis increases the size of mammary tumors, affecting the systemic response to the parasite. However, the parasite does not invade the tumor, and we decided to study if the excretion/secretion of antigens from Toxocara canis (EST) can affect the progression of mammary tumors or the pathophysiology of cancer which is metastasis. Thus, this study aimed to determine whether excretion/secretion T. canis antigens, injected directly into the tumor, affect tumor growth and metastasis., Methods: We evaluated these parameters through the monitoring of the intra-tumoral immune response., Results: Mice injected intratumorally with EST did not show changes in the size and weight of the tumors; although the tumors showed an increased microvasculature, they did develop increased micro and macro-metastasis in the lung. The analysis of the immune tumor microenvironment revealed that EST antigens did not modulate the proportion of immune cells in the tumor, spleen, or peripheral lymph nodes. Macroscopic and microscopic analyses of the lungs showed increased metastasis in the EST-treated animals compared to controls, accompanied by an increase in VEGF systemic levels., Discussion: Thus, these findings showed that intra-tumoral injection of T. canis EST antigens promote lung metastasis through modulation of the tumor immune microenvironment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Aragón-Franco, Ruiz-Manzano, Nava-Castro, Del Rìo Araiza, Garay-Canales, Pérez-Torres, Chacón-Salinas, Girón-Pérez and Morales-Montor.)