Adrenomedullin (ADM) is a peptide hormone produced primarily in the adrenal glands, playing a crucial role in various physiological processes. As well as improving vascular integrity and decreasing vascular permeability, ADM acts as a vasodilator, positive inotrope, diuretic, natriuretic and bronchodilator, antagonizing angiotensin II by inhibiting aldosterone secretion. ADM also has antihypertrophic, anti-apoptotic, antifibrotic, antioxidant, angiogenic and immunoregulatory effects and antimicrobial properties. ADM expression is upregulated by hypoxia, inflammation-inducing cytokines, viral or bacterial substances, strength of shear stress, and leakage of blood vessels. These pathological conditions are established during systemic inflammation that can result from infections, surgery, trauma/accidents or burns. The ability to rapidly identify infections and the prognostic, predictive power makes it a valuable tool in severe viral and bacterial infections burdened by high incidence and mortality. This review sheds light on the pathophysiological processes that in severe viral or bacterial infections cause endothelitis up to the development of organ damage, the resulting increase in ADM levels dosed through its more stable peptide mid-regional proadrenomedullin (MR-proADM), the most significant studies that attest to its diagnostic and prognostic accuracy in highlighting the severity of viral or bacterial infections and appropriate therapeutic insights.

Sepsis causes immune dysregulation and endotheliitis, with an increase in mid-regional pro-adrenomedullin (MR-proADM). The aim of the study is to determine an MR-proADM value that, in addition to clinical diagnosis, can identify patients with localized infection or those with sepsis/septic shock, with specific organ damage or with the need for intensive care unit (ICU) transfer and prognosis. The secondary aim is to correlate the MR-proADM value with the length of stay (LOS). In total, 301 subjects with sepsis (124/301 with septic shock) and 126 with localized infection were retrospectively included. In sepsis, MR-proADM ≥ 3.39 ng/mL identified acute kidney injury (AKI); ≥2.99 ng/mL acute respiratory distress syndrome (ARDS); ≥2.28 ng/mL acute heart failure (AHF); ≥2.55 ng/mL Glascow Coma Scale (GCS) < 15; ≥3.38 multi-organ involvement; ≥3.33 need for ICU transfer; ≥2.0 Sequential Organ Failure Assessment (SOFA) score ≥ 2; and ≥3.15 ng/mL non-survivors. The multivariate analysis showed that MR-proADM ≥ 2 ng/mL correlates with AKI, anemia and SOFA score ≥ 2, and MR-proADM ≥ 3 ng/mL correlates with AKI, GCS < 15 and SOFA score ≥ 2. A correlation between mortality and AKI, GCS < 15, ICU transfer and cathecolamine administration was found. In localized infection, MR-proADM at admission ≥ 1.44 ng/mL identified patients with AKI; ≥1.0 ng/mL with AHF; and ≥1.44 ng/mL with anemia and SOFA score ≥ 2. In the multivariate analysis, MR-proADM ≥ 1.44 ng/mL correlated with AKI, anemia, SOFA score ≥ 2 and AHF. MR-proADM is a marker of oxidative stress due to an infection, reflecting severity proportionally to organ damage.

Background: Suppression of Tumorigenicity 2 (ST2), a member of the interleukin-1 receptor family, plays a crucial role in immune regulation. Elevated sST2 levels are associated with poor prognosis in various inflammatory and cardiovascular diseases, including acute heart failure (AHF), sepsis and transplant rejection. Objectives and methods: This study aimed to evaluate the diagnostic and prognostic accuracy of sST2, along with other biomarkers, such as high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), procalcitonin (PCT) and mid-regional pro-adrenomedullin (MR-proADM), in patients with AHF, sepsis and AHF/sepsis overlap. Results: A cohort of 74 patients was analyzed, and comparison statistics revealed that sST2 levels were significantly higher in the AHF/sepsis group (113.88 ng/mL) compared to the AHF group (42.24 ng/mL, p = 0.024), while no significant difference was observed between sepsis and AHF groups (p = 0.10). Other biomarkers, including hs-CRP and PCT, showed significant differences between the AHF and AHF/sepsis groups. ROC curve analysis identified sST2 as a strong predictor of mortality and readmission, with high AUC values for 30-day readmission (0.821) and mortality (0.87). Conclusions: These findings suggest that combining biomarkers, including sST2, could improve the early diagnosis, risk stratification and management of critically ill patients with overlapping AHF and sepsis. Further studies with larger populations are needed to validate these findings and explore the potential of integrating these biomarkers into clinical practice.

Background: Anti-synthetase Syndrome (ASyS) is an idiopathic inflammatory myopathy characterized by muscle weakness and inflammatory infiltrates in muscles. Sjogren’s disease (SD) is an autoimmune condition primarily affecting exocrine glands. Both these conditions may present lung involvement. We describe a female patient with anti-synthetase/SD overlap syndrome and review the literature to identify published cases describing this overlap, aiming to better define its clinical, radiological, and serological features. Methods: The case description was based on a retrospective collection of clinical, laboratory, and imaging data related to the patient’s diagnostic process and clinical course. Data were anonymized and handled in accordance with the competent territorial Ethics Committee. A literature review was performed using the MEDLINE and Scopus databases by combining the keywords “Anti-Synthetase syndrome”, “Sjögren disease”, “Sjögren syndrome”, “Myositis”, and “Interstitial lung disease” (ILD). Published cases were selected if they met the 2016 EULAR/ACR criteria for SD and at least one of the currently proposed classification criteria for ASyS. Results: The described case concerns a 68-year-old woman with rapidly progressive ILD. The diagnosis of anti-synthetase/SD overlap syndrome was based on clinical, serological (anti-Ro52 and anti-PL7 antibodies), histological, and radiological findings. Despite immunosuppressive and antifibrotic treatment, the clinical course worsened, leading to a poor outcome. In addition, six relevant cases were identified in the literature. Clinical presentations, autoantibody profiles, radiological findings, and outcomes were highly heterogeneous. Among the reported cases, no standardized treatment protocols were adopted, reflecting the lack of consensus in managing this rare condition. Conclusions: In anti-synthetase/SD overlap syndrome, ILD may follow a rapidly progressive course. Early recognition can be challenging, especially in the absence of muscular involvement. This case-based review highlights the need for more standardized approaches to the diagnosis and management of this rare and complex overlap syndrome.