Granulomatous Panniculitis as a Complication of Subcutaneous Testosterone Pellet Therapy.

A 51-year-old man with a 3-year history of exogenous testosterone pellet injections to the left buttock presented for routine skin examination. While the patient reported recurrent drainage from the site of testosterone replacement therapy (TRT) injections, he continued to receive repeated implantations every 6 months. On physical examination, a 12-mm irregular, brown macule was identified within a poorly demarcated, ecchymotic, and fluctuant subcutaneous plaque on the left buttock with a sinus tract draining serosanguinous fluid. The pigmented lesion was biopsied, revealing malignant melanoma in situ; hence, a wide local excision was scheduled. During the procedure, necrotic subcutaneous fat was observed surrounding the site of biopsy, and a region measuring 18 cm2 approximately was debrided and submitted for pathologic evaluation. Histopathologic examination revealed a diffused subcutaneous granulomatous infiltrate with septal and lobular panniculitis and fat necrosis as well as peripherally palisading histiocytes and hemosiderin deposition (Figures 1A and B). Similar findings were observed in another specimen from the same segment of debrided tissue, compatible with granulomatous panniculitis. Periodic acid-Schiff (PAS), Gram's, and acid-fast bacilli (AFB) stains revealed no microorganisms. During surgical exploration, six foreign bodies were discovered and identified as undissolved testosterone pellets. The patient was referred to a wound care center, but ultimately lost to follow-up.

Evaluation of the Safety of Calcitonin Gene-Related Peptide Antagonists for Migraine Treatment Among Adults With Raynaud Phenomenon.

Importance: Calcitonin gene-related peptide (CGRP) antagonists have demonstrated tremendous promise in migraine management. However, these medications decrease reflex vasodilatory response, which may lead to exacerbation of microvascular disease in susceptible patients, such as patients with Raynaud phenomenon (RP). Objective: To investigate the microvascular complications of CGRP antagonists in patients with underlying RP. Design, Setting, and Participants: This retrospective cohort study was performed from May 18, 2018, to September 15, 2020, in Mayo Clinic Health System patients with Raynaud phenomenon while undergoing CGRP antagonist therapy to treat migraine. Inclusion criteria were age older than 18 years, history of migraine, past or current treatment with CGRP antagonists, and diagnosis of primary or secondary RP. Exposure: Treatment with CGRP antagonists. Main Outcomes and Measures: The main outcome measure was microvascular complications (eg, worsening RP, digital ulcerations, and gangrenous necrosis) after initiation of treatment with a CGRP antagonist. Patient demographic and clinical characteristics were compared between those who experienced complications and those who did not. Results: A total of 169 patients (163 [96.4%] female; 151 [89.3%] non-Hispanic White; mean [SD] age, 46 [13] years) were identified. Of the 169 patients, 9 (5.3%) exhibited microvascular complications, ranging from worsening RP to gangrene and autonecrosis that required distal digit amputation. Comparative analysis did not find statistically significant differences in demographic or clinical characteristics between the 2 cohorts. All 9 patients with complications were female (mean [SD] age, 40 [12] years). Five of the 9 patients (55.6%) had previously diagnosed RP; in 3 the RP was primary, and 2 it was secondary to scleroderma. The other 4 patients (44.4%) were newly diagnosed with RP. Eight of the 9 patients (88.9%) had chronic migraine; 4 had migraine with aura, and 5 had migraine without aura. The CGRP antagonist agents temporally associated with the microvascular complications included galcanezumab (in 3 patients), erenumab (in 5 patients), and fremanezumab (in 1 patient). Conclusions and Relevance: The results of this study indicate that microvascular complications of CGRP antagonist use in patients with underlying RP are uncommon. The incidence of serious adverse events, although rare, warrant caution when considering the use of these agents in patients with RP.

Irreversible Electroporation in Liver Cancers and Whole Organ Engineering.

Liver cancers contribute significantly to cancer-related mortality worldwide and liver transplants remain the cornerstone of curative treatment for select, early-stage patients. Unfortunately, because of a mismatch between demand and supply of donor organs, liver cancer patients must often wait extended periods of time prior to transplant. A variety of local therapies including surgical resection, transarterial chemoembolization, and thermal ablative methods exist in order to bridge to transplant. In recent years, a number of studies have examined the role of irreversible electroporation (IRE) as a non-thermal local ablative method for liver tumors, particularly for those adjacent to critical structures such as the vasculature, gall bladder, or bile duct. In addition to proving its utility as a local treatment modality, IRE has also demonstrated promise as a technique for donor organ decellularization in the context of whole-organ engineering. Through complete non-thermal removal of living cells, IRE allows for the creation of an acellular extra cellular matrix (ECM) scaffold that could theoretically be recellularized and implanted into a living host. Here, we comprehensively review studies investigating IRE, its role in liver cancer treatment, and its utility in whole organ engineering.

Radiogenomics and Radiomics in Liver Cancers.

Radiogenomics is a computational discipline that identifies correlations between cross-sectional imaging features and tissue-based molecular data. These imaging phenotypic correlations can then potentially be used to longitudinally and non-invasively predict a tumor's molecular profile. A different, but related field termed radiomics examines the extraction of quantitative data from imaging data and the subsequent combination of these data with clinical information in an attempt to provide prognostic information and guide clinical decision making. Together, these fields represent the evolution of biomedical imaging from a descriptive, qualitative specialty to a predictive, quantitative discipline. It is anticipated that radiomics and radiogenomics will not only identify pathologic processes, but also unveil their underlying pathophysiological mechanisms through clinical imaging alone. Here, we review recent studies on radiogenomics and radiomics in liver cancers, including hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and metastases to the liver.

Quadrilateral Space Syndrome: Diagnosis and Clinical Management.

Quadrilateral space syndrome (QSS) is a rare disorder characterized by axillary nerve and posterior humeral circumflex artery (PHCA) compression within the quadrilateral space. Impingement is most frequently due to trauma, fibrous bands, or hypertrophy of one of the muscular borders. Diagnosis can be complicated by the presence of concurrent traumatic injuries, particularly in athletes. Since many other conditions can mimic QSS, it is often a diagnosis of exclusion. Conservative treatment is often first trialed, including physical exercise modification, physical therapy, and therapeutic massage. In patients unrelieved by conservative measures, surgical decompression of the quadrilateral space may be indicated.

Triplet Separation Drives Singlet Fission after Femtosecond Correlated Triplet Pair Production in Rubrene.

Singlet fission, a multistep molecular process in which one photon generates two triplet excitons, holds great technological promise. Here, by applying a combination of transient transmittance and two-dimensional electronic spectroscopy with 5 fs laser pulses, we resolve the full set of fission steps before the onset of spin dephasing. In addition to its role as a viable singlet fission material, single-crystalline rubrene is selected because its energetics and transition dipole alignment uniquely allow for the unambiguous identification of the various fission steps through their contributions to distinct spectroscopic features. The measurements reveal that the neighboring correlated triplet pair achieves its maximum population within 20 fs. Subsequent growth of the triplet signal on picosecond time scales is attributable to spatial separation of the triplets, proceeding nonadiabatically through weakly coupled but near-resonant states. As such, we provide evidence in crystalline rubrene for a singlet fission step that, until now, has not been convincingly observed.