Ticagrelor: A Rare, Delayed Case of Angioedema.

Dual antiplatelet therapy (DAPT) with P2Y12 receptor inhibitors in conjunction with aspirin is the gold standard treatment for acute coronary syndrome (ACS) and to prevent stent thrombosis after percutaneous coronary intervention (PCI). While there have been reported allergic effects-particularly angioedema-linked to clopidogrel there is limited data on hypersensitivity reactions to ticagrelor. Here, we discuss a case of delayed-onset ticagrelor-induced angioedema in a patient, three weeks following initiation of DAPT with aspirin and ticagrelor status post-PCI with DES placement. The patient presented with acute onset tongue swelling and was successfully treated with epinephrine, steroids, and antihistamine. The C1 esterase inhibitor and tryptase levels were within normal limits. Ticagrelor was discontinued and the patient was transitioned to prasugrel for DAPT, without recurrence of symptoms. Given the few cases reported involving ticagrelor-induced angioedema, and the even rare, delayed onset cases such as those described above, it is imperative that clinicians be made aware of this adverse effect and its management.

Clinical Disease States Related to Mutations of the NOD2 Gene: A Case Report and Literature Review.

Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is a protein encoded by the NOD2 gene and plays an important role in the immune system. NOD2 is an intracellular pattern recognition receptor (PRR) responsible for the recognition of pathogens as well as the activation of many biochemical processes within cells of the host immune system. Mutations of the NOD2 gene can significantly impact the host's immune response against a variety of pathogens. In addition to immunodeficiency, mutations of the NOD2 gene have also been linked with several atopic diseases and autoimmune conditions such as rheumatoid arthritis and Crohn's disease (CD). There is also a distinct set of autoinflammatory conditions that are now classified as NOD2-associated autoinflammatory diseases (NAID). We present a case of a 63-year-old female with common variable immunodeficiency, eosinophilic asthma, and rheumatoid arthritis who was found to have a NOD2 mutation on genetic testing. As genetic testing continues to gain popularity, several disease states that were previously thought to be unrelated are now being recognized as originating from a common genetic defect.

Rapidly Progressive Glomerulonephritis: A COVID-19 Case Report.

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis is a systemic autoimmune disease that typically presents as a multi-organ manifesting disease of unclear etiology that can predispose to rapidly progressive glomerulonephritis (RPGN). If left untreated, ANCA-associated vasculitis can be fatal, and RPGN can progress to irreversible renal failure. Environmental and genetic factors have been implicated in the pathogenesis of this vasculitis. Coronavirus disease (COVID-19) has been noted to have various physiologic impacts on the body, with literature indicating possible autoimmune effects. We present a rare case of ANCA-associated vasculitis in an elderly male with no known autoimmune history after a recent illness with COVID-19. The patient had been seen as an outpatient with progressively declining renal function until he presented to the hospital with acute renal failure and pericarditis. Workup revealed elevated anti-myeloperoxidase antibody (MPO-AB) and perinuclear ANCA (p-ANCA) antibodies with a biopsy confirming focal cresenteric glomerulonephritis, and the patient was initiated on steroid therapy with notable improvement and a return to baseline kidney function.

Does the Combined Use of Aspirin and Immunotherapy Result in Better Outcomes in Non-Small Cell Lung Cancer Than Immunotherapy Alone?

INTRODUCTION:  Immunotherapy works by stimulating the immune system against cancer cells. Resistance to immunotherapy represents a significant challenge in the field of medical oncology. The mechanisms by which cancer cells evade immunotherapy are not well understood. Prior research suggested overexpression of prostaglandin E-2 (PGE-2) by cancer cells, which bind to EP-2 and EP-4 receptors on the tumor-specific cytotoxic T-lymphocytes (CTLs) and suppress their anticancer role. This immunosuppressive effect is involved in evading the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade of immunotherapy, which fuels cancer cell growth and recurrence. Studies found that combining PGE-2 blockade and a PD-1 signaling inhibitor helped promote the anticancer immunity cells. If confirmed in a clinical setting, the above in vitro findings could be of great clinical significance. METHODS:  Given that aspirin (ASA) blocks PGE-2 production, this work aimed to evaluate whether ASA use with immunotherapy results in better outcomes than immunotherapy alone. We performed a retrospective chart review of 500 non-small cell lung cancer (NSCLC) patients aged 21 years or older treated with PD-1 and/or PD-L1 directed immunotherapy at St. Luke's University Health Network between July 2015 and July 2021. Relevant patient, disease, and treatment-related variables were collected, including ASA use (≥ 81 mg daily) and the type of immunotherapy. Bivariate analyses were conducted to determine which variables to include in a multivariable model.  The four primary outcomes included survival at 18-months, both after diagnosis and starting immunotherapy, achieving complete remission (CR), and having a progressive disease (PD), as defined by RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Secondary outcomes included therapy-related toxicities and complications in the different treatment groups.   Results: After bivariate analysis, no statistical significance was found for a difference in 18-month survival between ASA and non-ASA groups (50.3% vs 49.7%, p-value = 0.79). ASA with PD-L1 inhibitor showed a trend towards a higher likelihood of achieving CR [adjusted odds ratio (AOR) 1.85] with a p-value close to statistical significance (0.06). However, ASA with PD-L1 showed high statistical significance as an independent variable associated with a decreased likelihood of having PD (AOR 0.44, p < 0.001). These findings suggest that NSCLC patients receiving PD-L1 inhibitors could benefit more from daily ASA than patients treated with PD-1 inhibitors. Our study emphasizes using the Eastern Cooperative Oncology Group (ECOG) scoring of the performance status (PS) in NSCLC patients. Poorer PS was associated with lower survival, decreased likelihood of CR, and more PD. Other variables associated with worse outcomes were advanced cancer stage at diagnosis and male gender. Low-PD-L1 expression in NSCLC was associated with an increased likelihood of survival; this could be of clinical significance, especially with previous studies suggesting better outcomes of using ASA in PD-L1 low tumors.  Conclusion: These findings suggest that daily ASA use with PD-L1 inhibitors is associated with more favorable outcomes in NSCLC. More studies are needed to investigate further the potential benefits vs. risks of using ASA with different immunotherapies and the other possible variables affecting treatment outcomes.

Tolerability of Six Months Indirect Cold (Physical) Plasma Treatment of the Scalp for Hair Loss.

Androgenetic alopecia (AGA) is a chronic form of hair loss. Cold atmospheric (physical) plasma (CAP) is partly ionized gas with various widely researched effects on living tissues. CAP is an emerging treatment modality in dermatology with uses for chronic leg ulcer, actinic keratosis, warts, and other applications. Its previously demonstrated ability to induce stem cell differentiation in various cell types makes CAP a possible treatment option for AGA. Directly creating CAP on the scalp surface has drawbacks, but indirect CAP treatment—when a CAP-treated liquid is used as topical therapy—offers an alternative. In a clinical pilot study, we treated 14 patients with AGA using the indirect CAP method for three months (4 patients) and six months (10 patients). The indirect CAP treatment was well tolerated and while the primary goal of the study was not to assess efficacy, most patients reported improvement, and the investigator’s assessment also showed improvement in most patients. Our findings create the foundation for longer, extensive trials to systematically assess the efficacy of indirect CAP treatment for AGA. ClinicalTrials.gov: NCT04379752 J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5186.