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Two series of novel Cu (II) (4a–e) and Ni (II) (5a–e) complexes bearing 1-(N-phenylthiocarbamoyl)-pyrazoline ligands (3a–e) were synthesized and characterized. The structures of Ni (II) complexes 5a, c were confirmed by X-ray crystallography; both complexes have a distorted octahedral coordination environment of the Ni (II); metal atoms are coordinated by pyridyl and pyrazoline nitrogen atoms and thiocarbonyl sulfur of two ligand moiety, with two chloride anions in the outer sphere. The Cu (II) complex 4a derived from ligand 3a demonstrate a non-typical electrochemical behavior indicating Cu (I) complex formation which can be explained either by pyrazoline ligand ring opening in DMF solution or by a non-innocent nature of 3a. All of the synthesized complexes were cytotoxic against HCT116 and К562 cell lines; the most cytotoxic ligand was 3d, which is structurally related to combretastatin A4.

The use of biocidal agents is a common practice for protection against biofouling in biomass-rich environments. In this paper, oligohexamethyleneguanidine (OHMG) polymer, known for its biocidal properties, was further modified with para-aminosalicylic acid (PAS) to enhance its properties against microorganisms coated with a lipid membrane. The structure of the product was confirmed by 1H NMR, 13C NMR, and FTIR spectroscopy. The values of the minimum inhibitory concentration (MIC) against Mycobacterium smegmatis ATCC 607 and Pseudomonas chlororaphis 449 were found to be 1.40 and 1.05 μg/mL, respectively. The synthesized substance was used as an additive to the polymer matrix of the composite optical oxygen sensor material. A series of samples with different contents of OHMG-PAS was prepared using a co-dissolution method implying the fabrication of a coating from a solution containing both polymers. It turned out that the mutual influence of the components significantly affects the distribution of the indicator in the matrix, surface morphology, and contact angle. The optimal polymer content turned out to be wt.3%, at which point the water contact angle reaches almost 122°, and the fouling rate decreases by almost five times, which is confirmed by both the respiratory MTT assay and confocal microscopy with staining. This opens up prospects for creating stable and biofouling-resistant sensor elements for use in air tanks or seawater.

Tubulin-targeting agents attract undiminished attention as promising compounds for the design of anti-cancer drugs. Verubulin is a potent tubulin polymerization inhibitor, binding to colchicine-binding sites. In the present work, a series of verubulin analogues containing a cyclohexane or cycloheptane ring 1,2-annulated with pyrimidine moiety and various substituents in positions 2 and 4 of pyrimidine were obtained and their cytotoxicity towards cancer and non-cancerous cell lines was estimated. The investigated compounds revealed activity against various cancer cell lines with IC50 down to 1–4 nM. According to fluorescent microscopy data, compounds that showed cytotoxicity in the MTT test disrupt the normal cytoskeleton of the cell in a pattern similar to that for combretastatin A-4. The hit compound (N-(4-methoxyphenyl)-N,2-dimethyl-5,6,7,8-tetrahydroquinazolin-4-amine) was encapsulated in biocompatible nanocontainers based on Ca2+ or Mg2+ cross-linked alginate and it was demonstrated that its cytotoxic activity was preserved after encapsulation.

The efficacy of photodynamic therapy (PDT) strictly depends on the availability of molecular oxygen to trigger the light-induced generation of reactive species. Fluorocarbons have an increased ability to dissolve oxygen and are attractive tools for gas delivery. We synthesized three fluorous derivatives of chlorin with peripheral polyfluoroalkyl substituents. These compounds were used as precursors for preparing nanoemulsions with perfluorodecalin as an oxygen depot. Therefore, our formulations contained hydrophobic photosensitizers capable of absorbing monochromatic light in the long wavelength region and the oxygen carrier. These modifications did not alter the photosensitizing characteristics of chlorin such as the generation of singlet oxygen, the major cytocidal species in PDT. Emulsions readily entered HCT116 colon carcinoma cells and accumulated largely in mitochondria. Illumination of cells loaded with emulsions rapidly caused peroxidation of lipids and the loss of the plasma membrane integrity (photonecrosis). Most importantly, in PDT settings, emulsions potently sensitized cells cultured under prolonged (8 weeks) hypoxia as well as cells after oxygen depletion with sodium sulfite (acute hypoxia). The photodamaging potency of emulsions in hypoxia was significantly more pronounced compared to emulsion-free counterparts. Considering a negligible dark cytotoxicity, our materials emerge as efficient and biocompatible instruments for PDT-assisted eradication of hypoxic cells.

2,4,6-Trichloro-1,3,5-triazine (cyanuric chloride) is an excellent coupling reagent for the preparation of highly structured multifunctional molecules. Three component systems based on porphyrin, cyanuric chloride and carborane clusters were prepared by a one-pot stepwise amination of cyanuric chloride with 5-(4-aminophenyl)-10,15,20-triphenylporphyrin, followed by replacement of the remaining chlorine atoms with carborane S- or N-nucleophiles. Some variants of 1,3,5-triazine derivatives containing porphyrin, carborane and residues of biologically active compounds such as maleimide, glycine methyl ester as well as thioglycolic acid, mercaptoethanol and hexafluoroisopropanol were also prepared. A careful control of the reaction temperature during the substitution reactions will allow the synthesis of desired compounds in a good to high yields. The structures of synthesized compounds were determined with UV-vis, IR, 1H NMR, 11B NMR, MALDI-TOF or LC-MS spectroscopic data. The dark and photocytotoxicity as well as intracellular localization and photoinduced cell death for compounds 8, 9, 17, 18 and 24 were evaluated.

Copper-containing agents are promising antitumor pharmaceuticals due to the ability of the metal ion to react with biomolecules. In the current study, we demonstrate that inorganic Cu2+ in the form of oxide nanoparticles (NPs) or salts, as well as Cu ions in the context of organic complexes (oxidation states +1, +1.5 and +2), acquire significant cytotoxic potency (2–3 orders of magnitude determined by IC50 values) in combinations with N-acetylcysteine (NAC), cysteine, or ascorbate. In contrast, other divalent cations (Zn, Fe, Mo, and Co) evoked no cytotoxicity with these combinations. CuO NPs (0.1–1 µg/mL) together with 1 mM NAC triggered the formation of reactive oxygen species (ROS) within 2–6 h concomitantly with perturbation of the plasma membrane and caspase-independent cell death. Furthermore, NAC potently sensitized HCT116 colon carcinoma cells to Cu–organic complexes in which the metal ion coordinated with 5-(2-pyridylmethylene)-2-methylthio-imidazol-4-one or was present in the coordination sphere of the porphyrin macrocycle. The sensitization effect was detectable in a panel of mammalian tumor cell lines including the sublines with the determinants of chemotherapeutic drug resistance. The components of the combination were non-toxic if added separately. Electrochemical studies revealed that Cu cations underwent a stepwise reduction in the presence of NAC or ascorbate. This mechanism explains differential efficacy of individual Cu–organic compounds in cell sensitization depending on the availability of Cu ions for reduction. In the presence of oxygen, Cu+1 complexes can generate a superoxide anion in a Fenton-like reaction Cu+1L + O2 → O2−. + Cu+2L, where L is the organic ligand. Studies on artificial lipid membranes showed that NAC interacted with negatively charged phospholipids, an effect that can facilitate the penetration of CuO NPs across the membranes. Thus, electrochemical modification of Cu ions and subsequent ROS generation, as well as direct interaction with membranes, represent the mechanisms of irreversible membrane damage and cell death in response to metal reduction in inorganic and organic Cu-containing compounds.

Outcomes for high-risk neuroblastoma have improved with the addition of antidisialoganglioside (GD2) antibody-mediated immunotherapy to multimodality therapy. Urticaria is an expected side effect of anti-GD2 immunotherapy. Rarely, despite maximal use of antihistamines and H2 receptor antagonists, refractory urticaria can result in impaired quality of life, and delays or discontinuation of immunotherapy. The anti-IgE monoclonal antibody, omalizumab, is approved for the treatment of asthma and chronic spontaneous urticaria. We successfully managed grade 3, naxitamab-related urticaria refractory to standard management in 2 patients using omalizumab, allowing for continued anti-GD2 immunotherapy. Omalizumab did not impact antitumor activity or immunogenicity of naxitamab., Competing Interests: M.L. declares consulting roles with Novartis. S.M. declares consulting roles with Ymabs Therapeutics, US WorldMeds, EUSA Pharma, and Innervate RP Inc. The remaining authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Chimeric antigen receptor T-cell (CAR-T) therapy, including axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel), has demonstrated significant efficacy in treating refractory or relapsed diffuse large B-cell lymphoma and B-cell acute lymphoblastic leukemia. Though adverse events such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are well characterized, the dermatologic adverse event (DAE) profile is less thoroughly described. This study aims to provide the first comprehensive analysis of DAEs associated with axi-cel and tisa-cel using real-world data from the FDA Adverse Event Reporting System (FAERS) database. FAERS database reports citing axi-cel or tisa-cel in patients aged 16 years or older were included, excluding duplicate reports and off-label indications. Disproportionality analysis by reporting odds ratio (ROR) was utilized to detect increased reporting of drug-adverse event combinations. Of the 11,256,845 reports in the FAERS database, 5559 identified CAR-T therapy as the primary suspected drug. After exclusions, 3,666 reports were analyzed (2,168 for axi-cel and 1,498 for tisa-cel). Among these, 2.7% of axi-cel and 5.1% of tisa-cel cases reported DAEs. There was a statistically significant increased reporting of 2 DAE groups associated with CAR-T therapy: severe cutaneous eruptions (ROR 5.18, 95% CI 1.29, 20.76) and vascular cutaneous (ROR 2.91, 95% CI 1.51, 5.60). The median time to DAE onset was 3 days after CAR T-cell infusion. Death was a reported outcome in 11.9% and 13.0% of axi-cel and tisa-cel DAE cases, respectively, and in 50% and 25% of severe cutaneous eruptions and vascular cutaneous cases, respectively. This study reveals a significantly increased reporting rate of severe cutaneous eruptions and vascular cutaneous DAEs associated with CAR-T therapy, with both event groups associated with high mortality. These results emphasize the importance of monitoring dermatologic toxicities in clinical practice to ensure timely identification and management of potentially severe adverse events., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Comprehensive genomic sequencing is becoming a critical component in the assessment of hematologic malignancies, with broad implications for patients' management. In this context, unequivocally discriminating somatic from germline events is challenging but greatly facilitated by matched analysis of tumor:normal pairs of samples. In contrast to solid tumors, in hematologic malignancies conventional sources of normal control material (peripheral blood, buccal swabs, saliva) could be highly involved by the neoplastic process, rendering them unsuitable. In this work we describe our real-world experience using cell-free DNA (cfDNA) isolated from nail clippings as an alternate source of normal control material, through the dedicated review of 2,610 tumor:nail pairs comprehensively sequenced by MSK-IMPACT-heme. Overall, we found that nail cfDNA is a robust germline control for paired genomic studies. In a subset of patients, nail DNA may be contaminated by tumor DNA, reflecting unique attributes of the hematologic disease and transplant history. Contamination is generally low level, but significantly more common among patients with myeloid neoplasms (20.5%; 304/1,482) than among those with lymphoid diseases (5.4%; 61/1,128) and particularly enriched in myeloproliferative neoplasms with marked myelofibrosis. When identified in patients with lymphoid and plasma-cell neoplasms, mutations commonly reflected a myeloid profile and correlated with a concurrent/evolving clonal myeloid neoplasm. Donor DNA was identified in 22% (11/50) of nails collected after allogeneic stem-cell transplantation. In this cohort, an association with a recent history of graft-versus-host disease was identified. These findings should be considered as a potential limitation to the use of nails as a source of normal control DNA but could also provide important diagnostic information regarding the disease process.

Graft-versus-host disease (GVHD) is a complication following allogeneic hematopoietic cell transplant that frequently causes multiorgan affection and decrease in quality of life. Global assessment and care of these patients require a multidisciplinary approach, but access to focused clinics is limited given their scarcity and location in major cities, as well as mobility and transportation challenges that frequently affect these patients. Thus, we established a multispecialty GVHD telehealth (TH) clinic and hypothesized that a virtual platform will expand access to clinical care in children and adults. The clinic team members included BMT specialist, nursing, dermatologist, dentist, nutritionist, physiatrist, research personnel, and others as needed. We evaluated all GVHD-related visits (in-person and TH) conducted in a single center from 01/2022 to 12/2022. Ninety-three patients received a total of 308 visits, and one-third were via TH. Approximately half of the in-person group had at least 1 TH visit, and 10 patients were seen exclusively via TH. Most patients had advanced chronic GVHD. More male patients were seen in GVHD clinic, but female patients had increased in clinic visits via TH (41% TH versus 32% in-person). One-third of clinic visits were from patients of racial and ethnic minorities. While only 6% (n = 12/217) of in-person visits were for patients living >100 miles from the center, 34% (n = 31/91) of TH visits were from far distances including out-of-state. At baseline, the most common patient-reported symptoms in a subset of patients included fatigue, disturbed sleep, and distress. Fifteen patients completed a follow-up symptom survey and reported significantly reduced distress regarding their GVHD (P = .02), although other symptoms remained stable. A multidisciplinary TH clinic provided care for adult and pediatric patients with GVHD. We demonstrated preliminary feasibility of building a robust TH platform with a collaborative multispecialty approach that allowed access and continuity of medical care. Gender inequalities were reduced, and distance to our center represented a lesser barrier to attending specialized care via TH. Additionally, patients reported a significant reduction in distress. Our findings support the ongoing development of a virtual platform to improve access to specialized GVHD care., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest Dr Markova is a consultant for ADC Therapeutics, Alira Health, AstraZeneca, Blueprint Medicines, Protagonist Therapeutics, OnQuality, Sanofi, and Janssen and receives royalties from UpToDate. Dr Lacouture is a consultant for Johnson and Johnson, Novocure, Janssen, Novartis, Deciphera, Kintara, RBC/La Roche Posay, Trifecta, Genentech, Loxo, Seattle Genetics, Lutris, OnQuality, Roche, Oncoderm, Apricity. Authors Chen and Lavin have no conflicts of interest to declare.

Background: Malignant wounds can present in up to 14.5% of patients with advanced cancer, significantly reducing quality of life (QoL). Management of malignant wounds is generally palliative, with the goal of improving or maintaining QoL. There is a lack of data on the impact of wound care clinics on QoL in patients with malignant wounds., Objectives: We sought to assess the QoL in patients with malignant wounds attending a wound care clinic. We also aimed to describe the baseline QoL, trends in QoL, physical symptoms, and treatment modalities that affect QoL in patients with malignant wounds over time., Methods: This retrospective observational study included 36 patients attending a wound care clinic at an oncologic hospital from 1/1/2016-4/1/2023. As part of the standard of care, these patients complete a Skindex-16 QoL survey at each visit. The Skindex-16 is a validated instrument to measure the effects of skin diseases on QoL. Data were extracted from the electronic medical record. Descriptive statistics, graphical methods, and random effects models for change were used to describe the patient population and the QoL measures over time., Results: Of the 36 patients who completed at least one Skindex-16 questionnaire, 69.4% were female, and 50.0% developed malignant wounds from breast cancer, 30.5% from nonmelanoma skin cancer, and 8.3% from sarcoma. At the initial visit, 86.1% of patients had exudate associated with their malignant wound, 52.7% of patients had malodor, 63.9% had bleeding, 69.4% had pain, and 50% had pruritus. The mean baseline Skindex-16 score was 54.5, falling into the "extremely severe" category, with a mean score of 15.4, 18.8, and 20.3 for the symptoms, emotions, and functioning domains, respectively. Nineteen patients completed at least one additional Skindex-16 questionnaire at follow-up visits (visit two 52.8%, visit three 33.3%, visit four 19.4%, visit five or greater 13.9%). Compared to the mean Skindex-16 score at baseline, there was an 18.5 point improvement at visit 2 (95% CI: 3.3-33.7, p = 0.018)., Conclusion: Malignant wounds severely adversely affect patients' quality of life. However, patients experienced improved quality of life after being treated at a dedicated wound clinic.

Levothyroxine (LT4), being "narrow therapeutic index" drug, may lead to significant fluctuations in thyroid stimulating hormone (TSH) levels. Such fluctuations can result in clinically noteworthy disruptions in thyroid function and give rise to adverse clinical consequences. Consequently, regulatory standards for LT4 potency have been tightened, with the most stringent specifications requiring maintenance of potency within the range of 95-105% of the labeled dose throughout the entire shelf-life of the product. The LT4 new formulation with tightened specification adheres to these rigorous standards, demonstrating established bioequivalence to its older formulation while upholding an equivalent standard of safety and efficacy. Furthermore, the novel formulation exhibits enhanced stability and an extended shelf-life. Of paramount significance is its capacity to provide patients with accurate and consistent dosing, thereby effectively catering to their medical requirements. The primary objective of the Asia-Pacific advisory board meeting (held in June 2022 with endocrinologists, experts from India, Indonesia, Philippines, Thailand, Malaysia and Singapore) was to establish the importance of appropriate communication to HCPs, patients and other stakeholders regarding the LT4 new formulation. The aim of this brief review is to highlight the importance of communication with healthcare professionals that should focus on providing accurate information on the LT4 new formulation, emphasizing efficacy, safety, and bioequivalence with clear guidance and ensure that patients and clinicians are fully informed about any changes to medications such as LT4 to reduce the risk of unrelated adverse events being incorrectly attributed to the newer formulation.

Purpose: Late alopecia, defined as incomplete hair regrowth > 6 months following cytotoxic chemotherapy or > 6 months from initiation of endocrine therapy, negatively impacts quality of life and may affect dose intensity of adjuvant therapy. This study investigates the effect of oral minoxidil in women with chemotherapy and/or endocrine therapy-induced late alopecia., Methods: The rate of clinical response was assessed by standardized photography and quantitated with trichoscopy., Results: Two hundred and sixteen patients (mean age 57.8 ± 13.7) were included. The most common cancer diagnosis was breast, in 170 patients (79.1%). Alopecia developed after chemotherapy in 31 (14.4%) patients, endocrine monotherapy in 65 (30.1%) patients, and chemotherapy followed by endocrine therapy in 120 (55.6%) patients. In 119 patients, standardized photography assessments were used to determine clinical change in alopecia after a median of 105 (IQR = 70) days on oral minoxidil and revealed improvement in 88 (74%) patients. Forty-two patients received quantitative trichoscopic assessments at baseline and at follow-up after a median of 91 (IQR = 126) days on oral minoxidil. Patients had clinically and statistically significant increases in frontal hair shaft density (from 124.2 hairs/cm 2 at initial to 153.2 hairs/cm 2 at follow-up assessment, p = 0.008) and occipital shaft density (from 100.3 hairs/cm 2 at initial to 123.5 hairs/cm 2 at follow-up assessment. p = 0.004). No patients discontinued oral minoxidil due to adverse events., Conclusions: Overall, oral minoxidil was well tolerated by patients and may benefit both frontal and occipital late alopecia in cancer survivors treated with cytotoxic and/or endocrine therapy by increasing hair shaft and follicle density., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Palmar-plantar erythrodysesthesia (PPE) is a slowly developing cutaneous reaction commonly experienced by patients treated with fluoropyrimidines. While erythrodysesthesia normally presents in a palmar-plantar distribution, it can also present with genital involvement, but this presentation is likely underreported and incorrectly attributed to an acute reaction from radiation therapy. This article aims to define erythrodysesthesia of the penis and scrotum as a rare but significant side effect of capecitabine., Case Presentation: We identified five cases of moderate to severe penis and scrotal erythrodysesthesia over a 2-year period at a large tertiary cancer center, representing an estimated incidence of 3.6% among male patients with rectal cancer who were treated with fluoropyrimidine-based chemoradiation within our institution., Conclusions: Improved understanding of erythrodysesthesia involving the penis and scrotum can facilitate early identification and treatment of symptoms, and possibly prevent the discontinuation or delay of cancer treatment in patients treated with capecitabine and similar drugs. These clinical advances would improve and prolong patient quality of life during cancer treatment and prevent complications that result in hospitalization., (© 2024. The Author(s).)

The introduction of immune checkpoint inhibitors (ICIs) has transformed the management of various malignancies. Alongside their therapeutic success, the widespread application of ICIs has unveiled a spectrum of immune-related adverse events (irAEs), most often affecting the skin. Cutaneous irAEs (cirAEs) encompass a range from common morbilliform and lichenoid rashes to more severe conditions such as bullous dermatoses and psoriasiform eruptions, each presenting distinct clinical challenges. Moreover, less common but clinically severe cutaneous reactions like toxic epidermal necrolysis have also been observed. cirAEs are frequently observed, with an incidence ranging from 37% to 70% for anti-cytotoxic T lymphocyte-associated antigen-4 antibodies and 17% to 40% for anti- programmed death-1/anti-programmed death ligand-1 antibodies. Recognizing the critical need for effective therapeutic strategies, this review carefully examines current approaches and guidelines for managing cirAEs., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

With an increasing number of patients eligible for immune checkpoint inhibitors, the incidence of immune-related adverse events (irAEs) is on the rise. Dermatologic immune-related adverse events (D-irAEs) are the most common and earliest to manifest, often with important downstream consequences for the patient. Current guidelines lack clarity in terms of diagnostic criteria for D-irAEs. The goal of this project is to better define D-irAE for the purposes of identification, diagnosis, and future study of this important group of diseases.The objectives of this project were to develop consensus guidance for an approach to D-irAEs including disease definitions and severity grading. Knowing that consensus among oncologists, dermatologists, and irAE subspecialists would be critical for usability, we formed a Dermatologic irAE Disease Definition Panel. The panel was composed of 34 experts, including oncologists, dermatologists, a rheumatologist, and an allergist/immunologist from 22 institutions across the USA and internationally. A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two virtual meetings to discuss areas of controversy. Panelists rated content for usability, appropriateness, and accuracy on 9-point scales in electronic surveys and provided free text comments. A working group aggregated survey responses and incorporated them into revised definitions. Consensus was based on numeric ratings using the RAND/UCLA Appropriateness Method with prespecified definitions.Following revisions based on panelist feedback, all items received consensus in the second round of ratings. Consensus definitions were achieved for 10 core D-irAE diagnoses: ICI-vitiligo, ICI-lichen planus, ICI-psoriasis, ICI-exanthem, ICI-bullous pemphigoid, ICI-Grover's, ICI-eczematous, ICI-eruptive atypical squamous proliferation, ICI-pruritus without rash, and ICI-erosive mucocutaneous. A standard evaluation for D-irAE was also found to reach consensus, with disease-specific exceptions detailed when necessary. Each disorder's description includes further details on disease subtypes, symptoms, supportive exam findings, and three levels of diagnostic certainty (definite, probable, and possible).These consensus-driven disease definitions standardize D-irAE classification in a useable framework for multiple disciplines and will be the foundation for future work. Given consensus on their accuracy and usability from a representative panel group, we anticipate that they can be used broadly across clinical and research settings., Competing Interests: Competing interests: MS: Consulting with Amgen, AbbVie, Arcutis, Bausch Health, Boehringer Ingelheim, Bristol-Myers-Squibb, Eli Lilly Canada, Fresenius Kabi Canada, Galderma, Incyte, Janssen, L’Oreal Canada, LEO Pharmaceuticals, Merck, Novartis, Pierre Fabre, Pfizer, Sanofi, Sun Pharmaceuticals, UCB Canada.LCC: Research funding- Bristol-Myers Squibb, Consulting- AmgenAM: Research Funding: Amryt Pharma, Incyte Corporation, Kintara Therapeutics, Novartis, Novocure Consulting: ADC Therapeutics, Alira Health, AstraZeneca, Blueprint Medicines, Protagonist Therapeutics, OnQuality, and Janssen Royalties: UpToDateCAN: CAN has received research grants from Boehringer Ingelheim and participated in an advisory board for work related to pustular psoriasis and palmoplantar pustulosis.VH: Royalties from UpToDateML: Research funding: Onquality, Novartis, AZ, Lutris, Novocure; Consulting: Onquality, Novartis, AZ, Lutris, Novocure, La Roche Posay, JanssenMC: PI for Blueprint, Cogent, Author for UpToDateNRL: Consultant for or has received honoraria from Seattle Genetics, Sanofi, Bayer, Seattle Genetics, Sanofi, Silverback and Synox Therapeutics outside the submitted work., (© 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.)

Purpose: The combination of trastuzumab and pertuzumab (HP) as part of a taxane-based regimen has shown benefit in the adjuvant and metastatic HER2 + breast cancer setting. In the CLEOPATRA trial, pruritus was reported in 11-17.6% of patients. The clinical phenotype and potential treatment strategies for this event have not been reported., Methods: A retrospective review of 2583 patients receiving trastuzumab and pertuzumab for the treatment of HER2 + breast cancer from 11/23/2011 to 6/21/2021 was performed at Memorial Sloan Kettering Cancer Center (MSKCC). Patient demographics, pruritus characteristics, and treatments as documented in the electronic medical record (EMR) were included in this analysis., Results: Of 2583 pts treated with HP, 122 (4.72%) with pruritus were identified. On average, patients experienced pruritus 319.0 days (8-3171) after initiation of HP. The upper extremities (67.4%), back (29.3%), lower extremities (17.4%), and shoulders (14.1%) were the most commonly affected regions. Grade 1/2 pruritus (97.6%) occurred in most cases. Patients responded primarily to treatment with topical steroids (52.2%), antihistamines (29.9%), emollients (20.9%), and gabapentinoids (16.4%). Of those with pruritus, 4 patients (3.3%) required treatment interruption or discontinuation., Conclusions: Pruritus is uncommon in patients on trastuzumab and pertuzumab, generally a chronic condition, with gabapentinoids or antihistamines representing effective therapies., (© 2023. The Author(s).)

Immune-related cutaneous adverse events (ircAEs) commonly occur in patients on treatment with immune checkpoint inhibitors and can significantly reduce patient quality of life. These are often treated with immunomodulatory agents, including glucocorticoids, immunosuppressants, and biologics. While often effective at managing symptoms, these therapies can cause several adverse events which may limit their use. In addition, immunomodulatory agents should be used with particular caution in patients receiving immunotherapy, as the efficacy of the oncologic regimen may potentially be undermined. In this review, we summarize the safety of systemic therapies that are used in the management of ircAEs, with a particular focus on the resultant risk of secondary tumor progression in patients with active cancer.

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a predominantly drug-induced disease, with a mortality rate of 15-20%, that engages the expertise of multiple disciplines: dermatology, allergy, immunology, clinical pharmacology, burn surgery, ophthalmology, urogynecology, and psychiatry. SJS/TEN has an incidence of 1-5/million persons per year in the United States, with even higher rates globally. One of the challenges of SJS/TEN has been developing the research infrastructure and coordination to answer questions capable of transforming clinical care and leading to improved patient outcomes. SJS/TEN 2021, the third research meeting of its kind, was held as a virtual meeting on August 28-29, 2021. The meeting brought together 428 international scientists, in addition to a community of 140 SJS/TEN survivors and family members. The goal of the meeting was to brainstorm strategies to support the continued growth of an international SJS/TEN research network, bridging science and the community. The community workshop section of the meeting focused on eight primary themes: mental health, eye care, SJS/TEN in children, non-drug induced SJS/TEN, long-term health complications, new advances in mechanisms and basic science, managing long-term scarring, considerations for skin of color, and COVID-19 vaccines. The meeting featured several important updates and identified areas of unmet research and clinical need that will be highlighted in this white paper., Competing Interests: KM was employed by Stevens-Johnson Syndrome Foundation. EJP reports grants from National Institutes of Health (R01HG010863, R01AI152183, U01AI154659) and from the National Health and Medical Research Council of Australia. She receives Royalties and consulting fees from UpToDate and has received consulting fees from Janssen, Verve, Biocryst, Regeneron, AstraZeneca and Novavax. The remaining 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. The reviewer OI declared a shared affiliation with the author AS to the handling editor at the time of review., (Copyright © 2023 Marks, Botta, Abe, Beachkofsky, Boothman, Carleton, Chung, Cibotti, Dodiuk-Gad, Grimstein, Hasegawa, Hoofnagle, Hung, Kaffenberger, Kroshinsky, Lehloenya, Martin-Pozo, Micheletti, Mockenhaupt, Nagao, Pakala, Palubinsky, Pasieka, Peter, Pirmohamed, Reyes, Saeed, Shupp, Sukasem, Syu, Ueta, Zhou, Chang, Becker, Bellon, Bonnet, Cavalleri, Chodosh, Dewan, Dominguez, Dong, Ezhkova, Fuchs, Goldman, Himed, Mallal, Markova, McCawley, Norton, Ostrov, Phan, Sanford, Schlundt, Schneider, Shear, Shinkai, Tkaczyk, Trubiano, Volpi, Bouchard, Divito and Phillips.)

Background: Cutaneous immune-related adverse events (cirAEs) remain a prevalent and common sequelae of immune checkpoint inhibitor (ICI) therapy, often necessitating treatment interruption and prolonged immune suppression. Treatment algorithms are still poorly defined, based on single-institution case reports without adequate safety assessments, and subject to publication bias., Methods: Data in this registry were collected through a standardized REDCap form distributed to dermatologists via email listserv., Results: Ninety-seven cirAEs were reported from 13 institutions in this registry. Topical and systemic steroids were the most common treatments used; however, targeted treatment matched to disease morphology was identified at numerous sites. Novel cirAE therapy uses that to our knowledge have not been previously described were captured including tacrolimus for the treatment of follicular, bullous, and eczematous eruptions and phototherapy for eczematous eruptions. Moreover, further evidence of cirAE treatment applications sparsely described in literature were also captured in this study including dupilumab and rituximab for bullous eruptions, phototherapy for lichenoid and psoriasiform eruptions, and acitretin for psoriasiform eruptions, among others. No serious adverse events were reported. Numerous targeted therapeutics including dupilumab, rituximab, and psoriasis biologics, among others, were associated with a cirAE grade improvement of ≥2 grades in every patient treated., Conclusion: This study suggests that a multi-institutional registry of cirAEs and management is not only feasible but that the information collected can be used to detect, evaluate, and rigorously assess targeted treatments for cirAEs. Further expansion and modification to include treatment progression may allow for sufficient data for specific treatment recommendations to be made., (© 2023 The Authors. International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Importance: Scoring systems for Stevens-Johnson syndrome and epidermal necrolysis (EN) only estimate patient prognosis and are weighted toward comorbidities and systemic features; morphologic terminology for EN lesions is inconsistent., Objectives: To establish consensus among expert dermatologists on EN terminology, morphologic progression, and most-affected sites, and to build a framework for developing a skin-directed scoring system for EN., Evidence Review: A Delphi consensus using the RAND/UCLA appropriateness criteria was initiated with a core group from the Society of Dermatology Hospitalists to establish agreement on the optimal design for an EN cutaneous scoring instrument, terminology, morphologic traits, and sites of involvement., Findings: In round 1, the 54 participating dermatology hospitalists reached consensus on all 49 statements (30 appropriate, 3 inappropriate, 16 uncertain). In round 2, they agreed on another 15 statements (8 appropriate, 7 uncertain). There was consistent agreement on the need for a skin-specific instrument; on the most-often affected skin sites (head and neck, chest, upper back, ocular mucosa, oral mucosa); and that blanching erythema, dusky erythema, targetoid erythema, vesicles/bullae, desquamation, and erosions comprise the morphologic traits of EN and can be consistently differentiated., Conclusions and Relevance: This consensus exercise confirmed the need for an EN skin-directed scoring system, nomenclature, and differentiation of specific morphologic traits, and identified the sites most affected. It also established a baseline consensus for a standardized EN instrument with consistent terminology.

Immune checkpoint inhibitors (ICI) target the PD-1/PD-L1 and CTLA-4 pathways and allows the immune system to deliver antitumor effects. However, it is also associated with well-documented immune-related cutaneous adverse events (ircAEs), affecting up to 70-90% of patients on ICI. In this study, we describe the characteristics of and patient outcomes with ICI-associated steroid-refractory or steroid-dependent ircAEs treated with dupilumab. Patients with ircAEs treated with dupilumab between March 28, 2017, and October 1, 2021, at Memorial Sloan Kettering Cancer Center were included in this retrospective study, which assessed the rate of clinical response of the ircAE to dupilumab and any associated adverse events (AEs). Laboratory values were compared before and after dupilumab. All available biopsies of the ircAEs were reviewed by a dermatopathologist. Thirty-four of 39 patients (87%, 95% CI: 73% to 96%) responded to dupilumab. Among these 34 responders, 15 (44.1%) were complete responders with total ircAE resolution and 19 (55.9%) were partial responders with significant clinical improvement or reduction in severity. Only 1 patient (2.6%) discontinued therapy due to AEs, specifically, injection site reaction. Average eosinophil counts decreased by 0.2 K/mcL (p=0.0086). Relative eosinophils decreased by a mean of 2.6% (p=0.0152). Total serum immunoglobulin E levels decreased by an average of 372.1 kU/L (p=0.0728). The most common primary inflammatory patterns identified on histopathological examination were spongiotic dermatitis (n=13, 33.3%) and interface dermatitis (n=5, 12.8%). Dupilumab is a promising option for steroid-refractory or steroid-dependent immune-related cutaneous adverse events, particularly those that are eczematous, maculopapular, or pruritic. Among this cohort, dupilumab was well-tolerated with a high overall response rate. Nonetheless, prospective, randomized, controlled trials are warranted to confirm these observations and confirm its long-term safety., Competing Interests: Competing interests: YJ receives research funding from Bayer, Bristol-Myers Squibb, Cycle for Survival, Department of Defense, Eli Lilly, Fred’s Team, Genentech/Roche, Merck, NCI, RGENIX, is on the advisory board or serves as a consultant for Amerisource Bergen, Arcus Biosciences, AstraZeneca, Basilea Pharmaceutica, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Geneos Therapeutics, GlaxoSmithKline, Imedex, Imugene, Lynx Health, Merck, Merck Serono, Mersana Therapeutics, Michael J. Hennessy Associates, Paradigm Medical Communications, PeerView Institute, Pfizer, Research to Practice, RGENIX, Seagen, Silverback Therapeutics, Zymeworks Inc., and has stock options with RGENIX. EAQ receives royalties from UpToDate. PC is a consultant for Merck, Immunocore, AstraZeneca, and Pfizer and has equity interest in Rgenix. MEL has a consultant role with Johnson and Johnson, Novocure, QED, Bicara, Janssen, Novartis, F. Hoffmann-LaRoche AG, EMD Serono, AstraZeneca, Innovaderm, Deciphera, DFB, Azitra, Kintara, RBC/La Roche Posay, Trifecta, Varsona, Genentech, Loxo, Seattle Genetics, Lutris, On Quality, Azitra, Roche, Oncoderm, NCODA, and Apricity. MEL receives research funding from Lutris, Paxman, Novocure, J&J, US Biotest, OQL, Novartis, and AstraZeneca. AM receives research funding from Incyte Corporation and Amryt Pharma; consults for Blueprint Medicines, ADC Therapeutics, Alira Health, OnQuality, Protagonist Therapeutics, and Janssen; and receives royalties from up to date., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Adoptive cellular immunotherapy, mainly hematopoietic stem cell transplant and CAR-T cell therapy have revolutionized treatment of patients with acute leukemia. Indications and inclusion criteria for these treatments have expanded in recent years. While these therapies are associated with significant improvements in disease response and overall survival, patients may experience adverse events from associated chemotherapy conditioning, engraftment, cytokine storm, supportive medications, and post-transplant maintenance targeted therapies. Supportive oncodermatology is a growing specialty to manage cutaneous toxicities resulting from the anti-cancer therapies. In this review, we summarize diagnosis and management of the common cutaneous adverse events including drug eruptions, graft-versus-host disease, neoplastic and paraneoplastic complications in patients undergoing cellular therapies., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Dermatologic adverse events (dAEs) occur frequently in hospitalized patients and can significantly reduce quality of life. Physicians grade dAEs using the Common Terminology Criteria of Adverse Events (CTCAE). However, they often underestimate symptom frequency and severity. The patient-reported outcomes (PRO) version of the CTCAE (PRO-CTCAE) was developed to assess symptoms from the patient's perspective. In this study, we assessed the patient-reported burden of dAEs via the PRO-CTCAE questionnaire and compared results with dAE assessment by treating oncologists and dermatologists., Methods: Patients admitted to Memorial Sloan Kettering Cancer Center from 6/1/2018 to 4/30/2019 and received a dermatology consultation were eligible. Once enrolled, participants completed a PRO-CTCAE questionnaire on 14 dermatologic symptoms. CTCAE grades assigned by oncology and dermatology were obtained from clinical notes, and kappa statistics were calculated to evaluate the level of agreement between physician and patient evaluations., Results: A total of 100 patients (mean age 59.4, 55% male) were prospectively enrolled. The most common patient-reported dAEs were rash (72%), swelling (67%), pruritus (64%), bruising (53%), and hives (37%). Oncologists and dermatologists underreported dAEs except for rash (median kappa values 0.3 [0.02-0.84] and 0.32 [0.02-0.87], respectively). Oncologists and dermatologists were concordant with each other's documented assessment of dAEs (median kappa value 0.985 [0.55-1])., Conclusion: Oncology patient-reported dAEs in a tertiary academic oncologic referral center were under-recognized by providers. PRO-CTCAE may be a useful tool to optimize inpatient dermatologic care for cancer patients by detecting and allowing management of patient-reported dAEs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A design of Pt(IV) prodrugs with tumor cell targeting moieties leading to increased selectivity is of interest. Herein, we designed a novel Pt(IV) prodrugs with COX-inhibitor naproxen, long-chain hydrophobic stearic acid moiety and biotin as axial ligands. We have established that for Pt(IV) prodrugs with biotin and naproxen or stearate in axial position, the lipophilicity rather than biotin receptors expression is the main factor of cytotoxicity. We also monitored the reduction speed of Pt(IV) prodrug 3 with naproxen and biotin in axial positions in A549 cells using XANES and demonstrated that the prodrug gradually releases cisplatin within 20 hours of incubation.

The rapid evolution of anti-cancer therapy (including chemotherapy, targeted therapy, and immunotherapy) in recent years has led to a more favorable efficacy and safety profile for a growing cancer population, and the improvement of overall survival and reduction of morbidity for many cancers. Anti-cancer therapy improves outcomes for cancer patients; however, many classes of anti-cancer therapy have been implicated in the induction of bullous dermatologic adverse events (DAE), leading to reduced patient quality of life and in some cases discontinuation of life-prolonging or palliative therapy. Timely and effective management of adverse events is critical for reducing treatment interruptions and preserving an anti-tumor effect. Bullous DAE may be limited to the skin or have systemic involvement with greater risk of morbidity and mortality. We present the epidemiology, diagnosis, pathogenesis, and management of bullous DAE secondary to anti-cancer therapies to enable clinicians to optimize management for these patients.