IgG4 serologic elevation in a patient with severe hidradenitis suppurativa: a case report and review of the literature.

Hidradenitis suppurativa (HS) is a chronic cutaneous and systemic inflammatory condition. Increasingly, reports have found that immunoglobulins play a role in the exaggerated immune response occurring in severe HS. It is important to recognize these implications as HS patients may present with laboratory abnormalities relating to chronic inflammation and immune activation. If these laboratory abnormalities are mistakenly associated with another disease process, it could lead to invasive workup and treatment, causing harm to patients. We describe the case of a 23-year-old woman with Hurley stage III HS who was hospitalized and found to have persistent immunoglobulin-G4 (IgG4) elevation. Upon discharge, the patient was diagnosed with IgG4-related disease (IgG4-RD) and started treatment with azathioprine. However, the biopsy ultimately was negative for IgG4-RD, and she presented to our clinic several months later with worsening HS disease during an active flare. Physical examination revealed actively draining nodules and sinus tracts in the bilateral axillae, inguinal folds, and mons pubis region. A confusing laboratory marker with HS was observed in this case. IgG4 has the potential to inhibit or activate inflammation depending on the context, and so IgG4 elevation has been noted in varying disease states. IgG4 elevation is observed in chronic inflammatory states and may represent a compensatory response by the body. While no other cases have reported the association between HS and IgG4 elevation, IgG levels have been found to reflect HS disease severity. Therefore, IgG4 could play a potential role in HS disease monitoring, and awareness of this association is important for providers when managing patients with HS.

Use of Albumin In Situ Hybridization to Diagnose Cutaneous Metastatic Hepatocellular Carcinoma With Poorly Differentiated Features: A Case Report and Review of the Literature.

ABSTRACT: Hepatocellular carcinoma (HCC) rarely metastasizes to the skin. When it occurs, it is often poorly differentiated making the diagnosis challenging. There exists a male predominance, and clinical presentation usually includes papules or nodules resembling pyogenic granulomas or dermal deposits. Histopathology shows malignant dermal cells. Hepatoid features including nests or cords of cells arranged in a trabecular or pseudoglandular pattern, sinusoidal formation, or the presence of bile exist in less than 50% of cases. Limitations exist with immunohistochemical staining, particularly in poorly differentiated neoplasms. Albumin in situ hybridization is more sensitive for detecting poorly differentiated HCC. Immunostaining in conjugation with albumin in situ hybridization enhances the detection of metastatic hepatocellular carcinoma. We report the case of a 74-year-old man with a history of HCC and a stable lung metastasis who presented with painful, growing bumps on his nose for 2 months. Examination revealed multiple, pink to white, shiny dermal-based papules with telangiectasias involving the right nasal tip and naris. Alpha-fetoprotein level was markedly elevated. Computed tomography showed expanding right lower lobe lung nodules. Histopathology of the cutaneous biopsy revealed features of a poorly differentiated basaloid carcinoma. Immunohistochemical staining was diffusely positive for glypican-3, focally positive for arginase-1, and negative for hepatocyte paraffin 1. Albumin in situ hybridization was diffusely positive, clinching the diagnosis of HCC. Metastatic HCC is a rare encounter for dermatopathologists. We aim to increase awareness of its occurrence in patients with advanced HCC and highlight the importance of clinical correlation when faced with poorly differentiated or unusual-looking basaloid neoplasms.

Large-bore Aspiration Thrombectomy with the FlowTriever System for the Treatment of Pulmonary Embolism: A Large Single-Center Retrospective Analysis.

PURPOSE: Evaluate the outcomes of patients undergoing large-bore aspiration thrombectomy for the treatment of pulmonary embolism at a large university medical center. MATERIALS AND METHODS: All patients treated for pulmonary embolism with the FlowTriever System (Inari Medical, Irvine, CA) between September 2019 and January 2023 were retrospectively analyzed. The primary safety and effectiveness outcomes included 7- and 30-day all-cause mortality, major bleeding, procedure-associated clinical decompensation, pulmonary vascular or cardiac injury, and pulmonary artery pressure reduction. Additional outcomes included technical success (completing thrombectomy with the device as intended), changes in hemodynamics and supplemental oxygen requirements, and postprocedural intensive care unit stay. RESULTS: A total of 286 patients were identified. The mean age was 60.5 years, and 90.9% of patients presented with intermediate-risk pulmonary embolism. Technical success was achieved in 96.9% (n = 277) of cases. The average reduction in mean pulmonary arterial pressure was 6.8 mmHg, from 28.7 ± 9.0 to 21.9 ± 8.0 mmHg (p < 0.0001). Two major bleeds (0.7%), 2 pulmonary vascular injuries (0.7%), and 4 (1.4%) procedure-associated decompensations were reported, but no device-related deaths occurred. The mean post-procedure intensive care unit stay was 2.0 ± 4.1 days, and 49.3% of patients had no postprocedural intensive care unit admittance. The overall 7-day and 30-day all-cause mortality rates were 2.4% and 6.7%, respectively, with a 30-day pulmonary embolism-related mortality rate of 3.5%. CONCLUSION: This non-industry-sponsored single-center analysis of large-bore aspiration thrombectomy in a large population corroborates the findings of other studies and confirms that this approach is safe and effective for the treatment high- and intermediate-risk pulmonary embolism. LEVEL OF EVIDENCE IV: Retrospective observational study.

Hybrid 18F-Fluoroethyltyrosine PET and MRI with Perfusion to Distinguish Disease Progression from Treatment-Related Change in Malignant Brain Tumors: The Quest to Beat the Toughest Cases.

Conventional MRI has important limitations when assessing for progression of disease (POD) versus treatment-related changes (TRC) in patients with malignant brain tumors. We describe the observed impact and pitfalls of implementing 18F-fluoroethyltyrosine (18F-FET) perfusion PET/MRI into routine clinical practice. Methods: Through expanded-access investigational new drug use of 18F-FET, hybrid 18F-FET perfusion PET/MRI was performed during clinical management of 80 patients with World Health Organization central nervous system grade 3 or 4 gliomas or brain metastases of 6 tissue origins for which the prior brain MRI results were ambiguous. The diagnostic performance with 18F-FET PET/MRI was dually evaluated within routine clinical service and for retrospective parametric evaluation. Various 18F-FET perfusion PET/MRI parameters were assessed, and patients were monitored for at least 6 mo to confirm the diagnosis using pathology, imaging, and clinical progress. Results: Hybrid 18F-FET perfusion PET/MRI had high overall accuracy (86%), sensitivity (86%), and specificity (87%) for difficult diagnostic cases for which conventional MRI accuracy was poor (66%). 18F-FET tumor-to-brain ratio static metrics were highly reliable for distinguishing POD from TRC (area under the curve, 0.90). Dynamic tumor-to-brain intercept was more accurate (85%) than SUV slope (73%) or time to peak (73%). Concordant PET/MRI findings were 89% accurate. When PET and MRI conflicted, 18F-FET PET was correct in 12 of 15 cases (80%), whereas MRI was correct in 3 of 15 cases (20%). Clinical management changed after 88% (36/41) of POD diagnoses, whereas management was maintained after 87% (34/39) of TRC diagnoses. Conclusion: Hybrid 18F-FET PET/MRI positively impacted the routine clinical care of challenging malignant brain tumor cases at a U.S. institution. The results add to a growing body of literature that 18F-FET PET complements MRI, even rescuing MRI when it fails.

Utilizing Stimuli Responsive Linkages to Engineer and Enhance Polymer Nanoparticle-Based Drug Delivery Platforms.

The devastating nature of cancer continues to be one of the leading causes of death in the world. Chemotherapy is among the most common forms of cancer treatment but comes with a host of adverse effects caused by the therapeutic agents damaging healthy tissue and organs. To limit these side effects, scientists have been designing stimuli responsive drug delivery vessels for targeted release. This Review focuses on the incorporation of stimuli responsive linkages in targeted drug delivery systems to enhance therapeutic efficiency. These platforms are primarily employed to control the distribution of anticancer agents in the body to reduce the adverse side effects caused by their toxicities. We will outline how drug delivery vessels are constructed so that exposure to select environmental and external stimuli releases the enclosed drug only at the target site. Stimuli responsive components are integrated within drug delivery vessels in the form of cross-linkers, polymers, and surface modifications. The changes, these moieties undergo upon stimuli exposure, cascade into larger scale alterations to the platforms, resulting in complete disassembly, reversible morphological variations, and enhanced cellular uptake. The ability for these modes of delivery to be initiated exclusively under stimuli exposure allows for release of toxic therapeutic agents to be confined only to the affected area.

Theranostics Based on Magnetic Nanoparticles and Polymers: Intelligent Design for Efficient Diagnostics and Therapy.

Theranostics is a fast-growing field due to demands for new, efficient therapeutics which could be precisely delivered to the target site using multimodal imaging with enhancing auxiliary actions. In this review article we discuss theranostic nanoplatforms containing polymers and magnetic nanoparticles along with other components. Magnetic nanoparticles allow for both diagnostic and therapeutic (hyperthermia) capabilities, while polymers can be reservoirs for drugs and are easily functionalized for cell targeting. We focus on the most important design strategies to achieve optimal theranostic effects as well as the roles of different components included in theranostics, reviewing the literature from the last 5 years.