Eosinophilic Fasciitis with Concurrent Necrobiotic Granulomatous Dermatitis Related to Checkpoint Inhibition Therapy.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapeutics. However, loss of physiologic tolerance in few cases has triggered rare and novel immune-related adverse events (irAEs). Eosinophilic fasciitis, an infrequently reported diffuse scleroderma-like entity, has been associated with ICI therapy. We report a case of a patient with metastatic melanoma treated with nivolumab who developed eosinophilic fasciitis with concurrent granulomatous dermatitis and lymphadenitis, the latter of which mimicked melanoma recurrence radiographically. Furthermore, this patient had a severe presentation that subsequently proved to be treatment-resistant to both corticosteroid and steroid-sparing therapies. To our knowledge, eosinophilic fasciitis has not been reported concurrently with granulomatous dermatitis in literature. We provide a narrative of this case and a review of therapeutic approaches for severe or refractory irAEs. With the increasing popularity of ICI therapy, we believe it is essential for clinicians to identify novel irAEs and be aware of treatments as late recognition could prove fatal.

A Comparison of Immobilised Triphenylphosphine and 1-Hydroxybenzotriazole as Mediators of Catch-and-Release Acylation Under Flow Conditions.

Described herein is a comparative study of immobilised triphenylphosphine (PS-PPh3 ) and 1-hydroxybenzotriazole (PS-HOBt) to mediate amide couplings under continuous flow. Compared to Appel-type amidations (PS-PPh3 ), the developed 'catch-and-release' approach (PS-HOBt) afforded near-quantitative amide conversions. Utilising this strategy, sulfonyl chloride amenability enabled facile access to an expanded library of sulfonate and sulfonamides. Post-constructional peptide modification was also demonstrated, affording two Nß -functionalised pentapeptides in high yields and purities. In contrast to frequently utilised coupling agents, the PS-HOBt resin could be recycled six times without a reduction in efficacy or regeneration requirements.

Unique Dermoscopic and Histopathologic Features of Melanoma Arising in a Patient With BAP1 Tumor Predisposition Syndrome.

Breast cancer gene 1 (BRCA1)-Associated Protein Tumor Predisposition Syndrome (BAP1-TPDS) is a relatively newly discovered syndrome that may develop a variety of malignancies, including atypical melanoma resembling Spitz nevi. Dermoscopic and molecular findings aid in diagnosing melanoma in BAP1-TPDS, and clinicians should have a high index of suspicion and a low threshold for screening and diagnostic testing for cutaneous malignancies in these patients. We describe an atypical, amelanotic melanoma in a 45-year-old male with a history of BAP1-TPDS and nodular melanoma. The patient presented with a rapidly evolving lesion on the right arm. Given the patient's prior history of melanoma and of heterozygous BAP1 gene mutation, histopathological and molecular analysis was performed on the lesion, revealing a diffuse loss of BAP1 expression and multiple chromosomal aberrancies. In these cases, histopathological and molecular analysis remain the keys to diagnosis, but astute dermoscopic evaluation may help clinicians avoid initial diagnostic confusion and delays in treatment. Melanoma should always be considered in patients with BAP1-TPDS, even in the absence of classic gross, dermoscopic, histopathological, and molecular characteristics of typical melanoma.

Immobilized Carbodiimide Assisted Flow Combinatorial Protocol to Facilitate Amide Coupling and Lactamization.

Through a screen of over one hundred and 30 permutations of reaction temperatures, solvents, carbodiimide resins, and carbodiimide molar equivalences, in the presence, absence, or combination of diisopropylamine and benzotriazole additives, a convenient and first reported carbodiimide polymer-assisted flow approach to effect amide coupling and lactamization was developed. The protocol entails injecting a single solution (1:9 dimethylformamide: dichloromethane) containing a carboxylic acid and an amine or linear peptide sequence into a continuous stream of dichloromethane. The protocol remained viable in the absence of base, did not require carboxylate preactivation which, and in concert with minimal workup requirements, enabled the isolation of products in high yields. Compared to the utilization of untethered carbodiimide reagents, the flow procedure was also observed to provide a degree of racemization safety.

Colonic and perianal ulceration exhibiting vacuolar interface dermatitis in the setting of HIV.

We report a case of noninfectious vacuolar interface dermatitis associated with colonic and perianal ulceration in a patient with acquired immunodeficiency syndrome (AIDS), which responded to immunosuppressive treatment. Our findings suggest that interface dermatitis in the setting of AIDS may warrant further gastrointestinal evaluation and may respond to immunosuppression.

Bariatric surgery prior to living donor nephrectomy: a solution to expand the living donor kidney pool - a retrospective study.

Most transplant centers decline morbidly obese people for living kidney donation. Their inclusion in the living donor pool after weight loss and reversal of comorbidities by bariatric surgery could reverse the downward living donation trend. We investigated whether bariatric surgery in the morbidly obese altered their candidacy for donation, complicated their subsequent donor nephrectomy, and impacted their early postoperative outcomes in a series of 22 donors who had bariatric surgery 0.7-22 years prior to laparoscopic living donor nephrectomy. Eighteen would have been excluded from donation prior to bariatric surgery based on a body mass index (BMI) > 40. Seventeen reached a BMI < 35 after bariatric surgery. One had hypertension that resolved after bariatric surgery. Prior bariatric surgery did not influence port placement and laterality of donor nephrectomy. None required open conversion or blood transfusion. In an exploratory comparison with 37 donors with a BMI 35-40, length of stay and warm ischemic time were shorter, blood loss and postoperative complications were similar, and operative time was longer. We therefore advocate the consideration of bariatric surgery in preparation for donation in morbidly obese people since it positively alters their candidacy without major impact on the subsequent living donor nephrectomy and early outcomes.

Deep transfer learning-based hologram classification for molecular diagnostics.

Lens-free digital in-line holography (LDIH) is a promising microscopic tool that overcomes several drawbacks (e.g., limited field of view) of traditional lens-based microcopy. However, extensive computation is required to reconstruct object images from the complex diffraction patterns produced by LDIH. This limits LDIH utility for point-of-care applications, particularly in resource limited settings. We describe a deep transfer learning (DTL) based approach to process LDIH images in the context of cellular analyses. Specifically, we captured holograms of cells labeled with molecular-specific microbeads and trained neural networks to classify these holograms without reconstruction. Using raw holograms as input, the trained networks were able to classify individual cells according to the number of cell-bound microbeads. The DTL-based approach including a VGG19 pretrained network showed robust performance with experimental data. Combined with the developed DTL approach, LDIH could be realized as a low-cost, portable tool for point-of-care diagnostics.

Subcutaneous scalp nodule as the presenting symptom of systemic light-chain amyloidosis.

We present a case of subcutaneous nodular amyloidosis mimicking a pilar cyst. Further evaluation led to the diagnosis of malignant systemic light-chain amyloidosis. The epidemiology and histopathological features of light-chain amyloidosis with cutaneous involvement are reviewed, as well as current recommendations for initial evaluation.

Erythema annulare centrifugum-type eruption in a patient undergoing cancer vaccine immunotherapy.

Sipuleucel-T is a cellular immunotherapy approved for the treatment of metastatic castration-resistant prostate cancer. We report a patient developing an immune related adverse effect from sipuleucel-T drug-induced erythema annulare centrifugum-like eruption. A brief review of the mechanism and implications of this eruption are also included.