Inflammation-Induced Coagulopathy Substantially Differs Between COVID-19 and Septic Shock: A Prospective Observational Study

Critical COVID-19, like septic shock, is related to a dysregulated systemic inflammatory reaction and is associated with a high incidence of thrombosis and microthrombosis. Improving the understanding of the underlying pathophysiology of critical COVID-19 could help in finding new therapeutic targets already explored in the treatment of septic shock. The current study prospectively compared 48 patients with septic shock and 22 patients with critical COVID-19 regarding their clinical characteristics and outcomes, as well as key plasmatic soluble biomarkers of inflammation, coagulation, endothelial activation, platelet activation, and NETosis. Forty-eight patients with matched age, gender, and co-morbidities were used as controls. Critical COVID-19 patients exhibited less organ failure but a prolonged ICU length-of-stay due to a prolonged respiratory failure. Inflammatory reaction of critical COVID-19 was distinguished by very high levels of interleukin (IL)-1β and T lymphocyte activation (including IL-7 and CD40L), whereas septic shock displays higher levels of IL-6, IL-8, and a more significant elevation of myeloid response biomarkers, including Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) and IL-1ra. Subsequent inflammation-induced coagulopathy of COVID-19 also differed from sepsis-induced coagulopathy (SIC) and was characterized by a marked increase in soluble tissue factor (TF) but less platelets, antithrombin, and fibrinogen consumption, and less fibrinolysis alteration. In conclusion, COVID-19 inflammation-induced coagulopathy substantially differs from SIC. Modulating TF release and activity should be evaluated in critical COVID-19 patients.

Biomarkers for sepsis: more than just fever and leukocytosis—a narrative review

A biomarker describes a measurable indicator of a patient's clinical condition that can be measured accurately and reproducibly. Biomarkers offer utility for diagnosis, prognosis, early disease recognition, risk stratification, appropriate treatment (theranostics), and trial enrichment for patients with sepsis or suspected sepsis. In this narrative review, we aim to answer the question, "Do biomarkers in patients with sepsis or septic shock predict mortality, multiple organ dysfunction syndrome (MODS), or organ dysfunction?" We also discuss the role of pro- and anti-inflammatory biomarkers and biomarkers associated with intestinal permeability, endothelial injury, organ dysfunction, blood–brain barrier (BBB) breakdown, brain injury, and short and long-term mortality. For sepsis, a range of biomarkers is identified, including fluid phase pattern recognition molecules (PRMs), complement system, cytokines, chemokines, damage-associated molecular patterns (DAMPs), non-coding RNAs, miRNAs, cell membrane receptors, cell proteins, metabolites, and soluble receptors. We also provide an overview of immune response biomarkers that can help identify or differentiate between systemic inflammatory response syndrome (SIRS), sepsis, septic shock, and sepsis-associated encephalopathy. However, significant work is needed to identify the optimal combinations of biomarkers that can augment diagnosis, treatment, and good patient outcomes.

Role of Biomarkers in the Integrated Management of Melanoma

Melanoma, which is an aggressive skin cancer, is currently the fifth and seventh most common cancer in men and women, respectively. The American Cancer Society reported that approximately 106,110 new cases of melanoma were diagnosed in the United States in 2021, with 7,180 people dying from the disease. This information could facilitate the early detection of possible metastatic lesions and the development of novel therapeutic techniques for melanoma. Additionally, early detection of malignant melanoma remains an objective of melanoma research. Recently, melanoma treatment has substantially improved, given the availability of targeted treatments and immunotherapy. These developments have highlighted the significance of identifying biomarkers for prognosis and predicting therapy response. Biomarkers included tissue protein expression, circulating DNA detection, and genetic alterations in cancer cells. Improved diagnostic and prognostic biomarkers are becoming increasingly relevant in melanoma treatment, with the development of newer and more targeted treatments. Here, the author discusses the aspects of biomarkers in the real-time management of patients with melanoma.

Electroconvulsive therapy effects on anhedonia and reward circuitry anatomy: a dimensional structural neuroimaging approach

Anhedonia is a core symptom of major depressive disorder (MDD) resulting from maladaptive reward processing. Electroconvulsive therapy (ECT) appears to be an effective treatment for patients with treatment-resistant depression (TRD). However, no previous neuroimaging studies have taken a dimensional approach to assess whether ECT-induced gray matter (GM) volume changes are specifically related to improvements in anhedonia and positive valence emotional constructs. Here we aimed to assess the relationship between right unilateral (RUL) ECT-induced brain volumetric changes and improvement in anhedonia and reward processing in patients with TRD. We evaluated 15 patients at two time points (before the first ECT session and after acute ECT completion) using magnetic resonance imaging (MRI), clinical scales (i.e., Quick Inventory of Depressive Symptomatology [QIDS] for syndromal depression severity and Snaith-Hamilton Pleasure Scale [SHAPS] for anhedonia) and the Temporal Experience of Pleasure Scale (TEPS) for anticipatory and consummatory experiences of pleasure. Patients with TRD showed a significant improvement in anhedonia symptoms and both anticipatory and consummatory pleasure after RUL ECT completion. Moreover, GM volume increases within the right reward system were related to anhedonia responders and, specifically, improvement in anticipatory (but not consummatory) reward. We highlight the importance of a dimensional and circuit-based approach to understanding target engagement and the mechanism of action of ECT, with the goal to define symptom- and circuit-specific response biomarkers for device neuromodulation therapies.

Fluid Biomarkers for Monitoring Structural Changes in Polyneuropathies: Their Use in Clinical Practice and Trials

Reliable and responsive tools for monitoring disease activity and treatment outcomes in patients with neuropathies are lacking. With the emergence of ultrasensitive blood bioassays, proteins released with nerve damage are potentially useful response biomarkers for many neurological disorders, including polyneuropathies. In this review, we provide an overview of the existing literature focusing on potential applications in polyneuropathy clinical care and trials. Whilst several promising candidates have been identified, no studies have investigated if any of these proteins can serve as response biomarkers of longitudinal disease activity, except for neurofilament light (NfL). For NfL, limited evidence exists supporting a role as a response biomarker in Guillain-Barré syndrome, vasculitic neuropathy, and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Most evidence exists for NfL as a response biomarker in hereditary transthyretin-related amyloidosis (hATTR). At the present time, the role of NfL is therefore limited to a supporting clinical tool or exploratory endpoint in trials. Future developments will need to focus on the discovery of additional biomarkers for anatomically specific and other forms of nerve damage using high-throughput technologies and highly sensitive analytical platforms in adequality powered studies of appropriate design. For NfL, a better understanding of cut-off values, the relation to clinical symptoms and long-term disability as well as dynamics in serum on and off treatment is needed to further expand and proceed towards implementation.

Efficacy and Response Biomarkers of Apatinib in the Treatment of Malignancies in China: A Review

Apatinib is a multitarget tyrosine kinase inhibitor marketed in China for the treatment of advanced gastric cancer (GC) and hepatocellular carcinoma (HCC). It has also been used off-label for the treatment of many other malignancies. To comprehensively evaluate the efficacy of apatinib as a targeted therapy in the treatment of malignancies, we conducted systematic online and manual searches of the literature on apatinib in the treatment of malignancies. In this review, we first summarized the efficacy of apatinib against various malignancies based on clinical trials where results have been reported. In prospectively registered trials, apatinib has been proven to be effective against GC, HCC, lung cancer, breast cancer, sarcoma, esophageal cancer, colorectal cancer, ovarian cancer, cervical cancer, cholangiocarcinoma, diffuse large B-cell lymphoma, nasopharyngeal carcinoma, and differentiated thyroid cancer. The response biomarkers for apatinib were also reviewed. This review will serve as a good reference for the application of apatinib in clinical studies and the design of clinical trials.

Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis

We performed a retrospective analysis of angiosarcoma (AS) genomic biomarkers and their associations with the site of origin in a cohort of 143 cases. Primary sites were head and neck (31%), breast (22%), extremity (11%), viscera (20%), skin at other locations (8%), and unknown (9%). All cases had Next Generation Sequencing (NGS) data with a 592 gene panel, and 53 cases had Whole Exome Sequencing (WES) data, which we used to study the microenvironment phenotype. The immunotherapy (IO) response biomarkers Tumor Mutation Burden (TMB), Microsatellite Instability (MSI), and PD-L1 status were the most frequently encountered alteration, present in 36.4% of the cohort and 65% of head and neck AS (H/N-AS) (p < 0.0001). In H/N-AS, TMB-High was seen in 63.4% of cases (p < 0.0001) and PDL-1 positivity in 33% of cases. The most common genetic alterations were TP53 (29%), MYC amplification (23%), ARID1A (17%), POT1 (16%), and ATRX (13%). H/N-AS cases had predominantly mutations in TP53 (50.0%, p = 0.0004), POT1 (40.5%, p < 0.0001), and ARID1A (33.3%, p = 0.5875). In breast AS, leading alterations were MYC amplification (63.3%, p < 0.0001), HRAS (16.1%, p = 0.0377), and PIK3CA (16.1%, p = 0.2352). At other sites, conclusions are difficult to generate due to the small number of cases. A microenvironment with a high immune signature, previously associated with IO response, was evenly distributed in 13% of the cases at different primary sites. Our findings can facilitate the design and optimization of therapeutic strategies for AS.

Dark Side of Cancer Therapy: Cancer Treatment-Induced Cardiopulmonary Inflammation, Fibrosis, and Immune Modulation

Advancements in cancer therapy increased the cancer free survival rates and reduced the malignant related deaths. Therapeutic options for patients with thoracic cancers include surgical intervention and the application of chemotherapy with ionizing radiation. Despite these advances, cancer therapy-related cardiopulmonary dysfunction (CTRCPD) is one of the most undesirable side effects of cancer therapy and leads to limitations to cancer treatment. Chemoradiation therapy or immunotherapy promote acute and chronic cardiopulmonary damage by inducing reactive oxygen species, DNA damage, inflammation, fibrosis, deregulation of cellular immunity, cardiopulmonary failure, and non-malignant related deaths among cancer-free patients who received cancer therapy. CTRCPD is a complex entity with multiple factors involved in this pathogenesis. Although the mechanisms of cancer therapy-induced toxicities are multifactorial, damage to the cardiac and pulmonary tissue as well as subsequent fibrosis and organ failure seem to be the underlying events. The available biomarkers and treatment options are not sufficient and efficient to detect cancer therapy-induced early asymptomatic cell fate cardiopulmonary toxicity. Therefore, application of cutting-edge multi-omics technology, such us whole-exome sequencing, DNA methylation, whole-genome sequencing, metabolomics, protein mass spectrometry and single cell transcriptomics, and 10 X spatial genomics, are warranted to identify early and late toxicity, inflammation-induced carcinogenesis response biomarkers, and cancer relapse response biomarkers. In this review, we summarize the current state of knowledge on cancer therapy-induced cardiopulmonary complications and our current understanding of the pathological and molecular consequences of cancer therapy-induced cardiopulmonary fibrosis, inflammation, immune suppression, and tumor recurrence, and possible treatment options for cancer therapy-induced cardiopulmonary toxicity.