Tumor therapeutic response monitored by telemetric temperature sensing, a preclinical study on immunotherapy and chemotherapy.

Temperature in the body and the tumor reflects physiological and pathological conditions. A reliable, contactless, and simplistic measurement system can be used for long-term monitoring of disease progression and therapy response. In this study, miniaturized battery-free wireless chips implanted into growing tumors on small animals were used to capture both basal and tumor temperature dynamics. Three preclinical models: melanoma (B16), breast cancer (4T1), and colon cancer (MC-38), were treated with adoptive T cell transfer, AC-T chemotherapy, and anti-PD-1 immunotherapy respectively. Each model presents a distinctive pattern of temperature history dependent on the tumor characteristic and influenced by the administered therapy. Certain features are associated with positive therapeutic response, for instance the transient reduction of body and tumor temperature following adaptive T cell transfer, the elevation of tumor temperature following chemotherapy, and a steady decline of body temperature following anti-PD-1 therapy. Tracking in vivo thermal activity by cost-effective telemetric sensing has the potential of offering earlier treatment assessment to patients without requiring complex imaging or lab testing. Multi-parametric on-demand monitoring of tumor microenvironment by permanent implants and its integration into health information systems could further advance cancer management and reduce patient burden.

The mixed spongiotic and interface reaction pattern: A study of clinical and histopathologic findings.

BACKGROUND: Categorization of biopsy specimens into inflammatory reaction patterns is central to dermatopathologic assessment. Mixed inflammatory patterns are poorly characterized and may represent clinicopathologic challenges. The purpose of this study was to identify clinical and histopathologic findings associated with the mixed spongiotic-interface dermatitis (SID) histopathologic pattern. METHODS: Fifty-one institutional biopsy specimens of SID were identified over a 2-year period by retrospective natural language search. Histopathologic and clinical features were identified. RESULTS: The most common histopathologic features associated with SID were mild spongiosis (51%), focal vacuolar interface change (72%), lymphocytic exocytosis (92%), and superficial-dermal lymphocytic infiltrate (94%) with variable eosinophils (61%). Clinically, 80% of subjects presented with a symmetric morbilliform eruption. Polypharmacy (94%), immunosuppression (47%), and history of malignancy (47%) were common. The most common diagnoses were drug reaction (37%), possible drug reaction (12%), and viral exanthem (12%). Drug reaction with eosinophilia and systemic symptoms represented 25% of all confirmed cutaneous adverse drug reactions (CADR). Average time from drug initiation to symptom initiation was 20 days (SD: 22.3, range: 0-90); median disease duration was 25.5 days. Spongiotic vesicles and Langerhans cells were less common in patients with a strong clinicopathologic diagnosis of drug reaction compared to non-drug eruptions (p = 0.04). CONCLUSIONS: The mixed SID pattern is commonly encountered in CADR but may represent a more subacute course, implying consideration for inciting medication(s) started before the typical 7- to 14-day window.

A Fatal Case of Diffuse Alveolar Hemorrhage in the Setting of Systemic Lupus Erythematosus: A Case Report and Review of Noninfectious Causes of Acute Pulmonary Hemorrhage in Adults.

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease, characterized by autoantibody production and immune complex formation, that has the potential to affect virtually any organ. Pleuropulmonary involvement occurs in 50-70% and commonly manifests as pleuritis and pleural effusion. Diffuse alveolar hemorrhage (DAH) is a rare manifestation of SLE. Most cases of DAH occur in young adults with an underlying autoimmune disease such as systemic vasculitis or Goodpasture syndrome. SLE is typically lower on the list of initial differential diagnoses of DAH due to its rarity compared to other etiologies. We present a case of a patient with dyspnea on exertion, dry coughs, lower extremity edema, and intermittent periorbital edema who ultimately succumbed to respiratory failure secondary to DAH in the setting of SLE. The diagnosis of SLE was suspected clinically and confirmed at autopsy due to her rapid clinical deterioration. DAH requires prompt intervention, and management is guided by the underlying disease process. SLE is a potentially treatable disease; therefore, timely diagnosis is important in order to exclude other noninfectious causes of DAH (reviewed in this report) and to initiate appropriate therapy.

The antinuclear antibody dense fine speckled pattern and possible clinical associations: An indication of a proinflammatory microenvironment.

BACKGROUND: Indirect immunofluorescence (IIF) is the most prevalent screening antinuclear antibody test for systemic autoimmune rheumatic disease (SARD). Certain IIF patterns have known antibody and disease associations, but the dense fine speckled (ANA-DFS) pattern has no confirmed clinical associations. Our objective was to determine the prevalence of SARD among a group of ANA-DFS positive individuals and to identify final diagnoses among non-SARD individuals in order to determine possible clinical associations with the ANA-DFS pattern. METHODS: A retrospective study of 425 patients from a university health care system with a positive ANA-DFS pattern consecutively between August 2017 and September 2018. Sera samples underwent ANA testing by IIF on HEp-2 cell substrates (Euroimmun, Germany). Clinical information was retrieved from electronic health records and stored in a de-identified database. RESULTS: The prevalence of SARD was 24%. Undetermined diagnosis (17%), skin disorders (12.1%), and fibromyalgia/chronic pain syndrome/chronic fatigue syndrome (11.8%) were the most common non-SARD diagnoses. Taking into account past medical history, the most common non-SARD were atopic disorders (21.2%), fibromyalgia/chronic pain syndrome/chronic fatigue syndrome (17.6%), and skin disorders (16.7%). CONCLUSIONS: The ANA-DFS pattern may be indicative of an underlying antigen-antibody interaction that plays a role in either the initiation or propagation of immunologic reactions. DFS70/LEDGF is a transcription factor involved in cell survival and stress protection, and autoantibodies may inhibit its function. It is likely that there are other antibodies producing the ANA-DFS pattern besides anti-DFS70/LEDGF, and more research is necessary to identify additional antibody specificities. The ANA-DFS pattern may be an indicator of a proinflammatory microenvironment given the high frequency of symptomatic patients and disease processes with an immunologic basis (including SARD).