Rebalanced hemostasis in advanced liver disease: thromboelastography vs. standard coagulation tests

Datele publicate în ultimul deceniu sugerează că evaluarea hemostazei la pacienții cu boală hepatică avansată (BHA) utilizând probele de coagulare standard (timp de protrombină, INR, numărul trombocitelor) nu reflectă fidel statusul coagulării. Deși istoric se presupunea că pacienții cu ciroză hepatică sunt ”anticoagulați spontan”, fapt sugerat de frecvența evenimentelor hemoragice și alterarea coagulogramei standard, s-a constatat de asemenea și o incidență crescută a evenimentelor trombotice, atât în teritoriul splanhnic (tromboza sistemului venos portal), cât și în circulația sistemică. Pornind de la aceste premise, s-a dovedit faptul că pacienții cu BHA au un profil hemostatic reechilibrat, care compensează diminuarea cantitativă a factorilor procoagulanți sintetizați în ficat cu modificări secundare în cascada coagulării. Dezavantajul major al probelor de coagulare standard este reprezentat de evaluarea exclusivă a deficitului de factori procoagulanți, ilustrând astfel doar una dintre fațetele coagulării la pacienții cu BHA. Metodele viscoelastice de evaluare a coagulării, precum tromboleastografia (TEG) sau trombelastometria rotațională (ROTEM), permit evaluarea globală a procesului de coagulare, evaluând toate etapele coagulării (de la formarea trombului la fibrinoliză) și analizând atât elementele pro- cât și anticoagulante. Astfel, utilizând TEG, se poate efectua o apreciere adecvată a riscului hemoragic sau protrombotic, evitând administrarea excesivă de preparate sanguine precum plasma proaspătă congelată, crioprecipitat sau masă trombocitară, care au potențialul de a agrava hipertensiunea portală.Increasing evidence suggests that standard coagulation tests - SCTs (prothrombin time, INR, platelet count) fail to adequately assess hemostasis in patients with advanced liver disease (ALD). According to the prior paradigm, cirrhotic patients were considered ”spontaneously anticoagulated”, an assumption based on the relative frequency of bleeding events and the alteration of SCTs. However, these patients also have a higher incidence of thrombotic events in the splanchnic venous system and systemic circulation. Based on these grounds, research has shown that ALD patients have a rebalanced hemostatic profile, as secondary alterations in the coagulation system compensate for the decrease in liver-derived procoagulant factors. The major caveat in using SCTs in cirrhosis derives from their failure to assess hemostasis beyond the deficit in procoagulant factors. Viscoelastic tests, such as thromboelastography (TEG) or rotational thromboelastometry (ROTEM), can provide a global assessment of hemostasis, evaluating the entire coagulation process (from clot formation to fibrinolysis) as well as the balance of pro- and anticoagulant factors. Therefore, a TEG-based coagulation assessment can limit unnecessary blood product use (such as fresh frozen plasma, cryoprecipitate, or platelets), thus preserving a scarce resource and limiting the detrimental effects of transfusions

Predictive Factors for the Positivity of the Sentinel Lymph Node in Malignant Melanoma

Malignant melanoma is a neoplasia that has its origin in the melanocytes, the melanin-synthesizing pigment cells present in the epidermis or sometimes in the dermis. Sentinel lymph node biopsy (SLNB) is the standard procedure used for staging patients with malignant melanoma in the majority of surgical centers in the world. With a probability of approximately 20% of finding positive lymph nodes, it spares a large number of patients of a complete lymphatic dissection. The aim of this study is to evaluate the factors that can predict the positivity of sentinel lymph nodes in malignant melanoma patients. We performed a retrospective study analyzing the histopathologic reports of patients who underwent SLNB for malignant melanoma between 2012 and 2015. There were 32 patients identified, out of which only three (9.37%) had positive SLN, so the majority of our patients were spared of regional lymphatic dissection. In our series, lymphatic invasion (p = 0.01), Breslow index >4 mm (p = 0.0064), AJCC staging (p = 0.0008), the presence of precursory lesions (p = 002), and microsatellitosis (p = 0.017) were predictive factors for the positivity of the SLN in malignant melanoma patients. Although our results are similar to those published in the literature, we consider that larger cohort studies should be performed to consolidate our results

The Role of Immunohistochemistry in the Differential Diagnosis between Intrahepatic Cholangiocarcinoma, Hepatocellular Carcinoma and Liver Metastasis, as Well as Its Prognostic Value

Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent primary hepatic malignant tumor, after hepatocellular carcinoma (HCC). Its incidence has risen worldwide, yet the only potentially curative treatment, surgical resection, is seldom applicable, and the median overall survival remains extremely low. So far, there are no personalized therapy regimens. This study investigated whether routine immunohistochemical stains have diagnostic and/or prognostic value in iCCA. Clinical, imaging, and pathology data were retrospectively gathered for patients diagnosed with iCCA, HCC, or liver metastases assessed using liver needle biopsies. Three study groups with an equal number of cases (n = 65) were formed. In the iCCA group, CK19, CA19-9, CK7, and CEA demonstrated the highest sensitivities (100%, 100%, 93.7%, and 82.6%, respectively). The most relevant stains used for diagnosing HCCs were Glypican 3, CD34 (sinusoidal pattern), and Hep Par 1, with corresponding sensitivities of 100%, 100%, and 98.2%. The immunohistochemical panels for diagnosing metastatic tumors were chosen after correlating the clinical data and morphologic H&E aspects. Moderate/intensely positive CK7 expression and absent/low amount of intratumoral immune cells were favorable prognostic factors and correlated with increased overall survival in both the univariate analysis and the multivariate regression adjusted for age, existence of cirrhosis, number of tumors, and tumor differentiation

Unveiling Health Inequalities: Exploring Metabolic Dysfunction in Rural Roma Communities

Background: Europe’s largest ethnic minority, the Roma, are often confronted with substantial obstacles that result in health disparities. Research indicates that there are elevated rates of both communicable and non-communicable diseases, such as metabolic syndrome (MetS), among Roma communities, often linked to living conditions, limited education, or poverty. This study centers on remote rural Roma settlements in Romania, evaluating the prevalence of metabolic dysfunction, obesity, and liver steatosis while considering socio-economic and lifestyle factors. Methods: Over a period of 36 months, local visits to a total of 25 rural Roma communities were conducted, where a medical team gathered information through a standardized questionnaire and conducted a physical exam on every participant. Liver steatosis was also recorded with the help of a portable wireless ultrasound device. Results: Our study included 343 participants, with a predominance of female subjects, representing 72.5% (n = 249) of the patients. The prevalence of obesity, defined by a body mass index (BMI) above 30 kg/m2, was 32.2% (n = 111). Arterial hypertension was found to have a prevalence of 54.1% (n = 185), with de novo hypertension being observed in 19.2% patients (n = 66). Type 2 diabetes mellitus was found in 28.9% patients (n = 99), with 19.5% being de novo cases. The prevalence of hepatic steatosis was 57.2% (n = 111/194). A positive association between metabolic features and at-risk behaviors was found. Conclusions: This study underscores the transition from infectious to metabolic diseases in vulnerable communities and highlights the urgency of targeted public health strategies tailored to the unique needs of rural Roma populations, aiming to mitigate health disparities and promote equitable healthcare access

The Dynamics of the Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios Predict Progression to Septic Shock and Death in Patients with Prolonged Intensive Care Unit Stay

Background and objectives: The prognoses of patients experiencing a prolonged stay in the intensive care unit (ICU) are often significantly altered by hospital-acquired infections (HAIs), the early detection of which might be cumbersome. The aim of this study was to investigate the roles of the neutrophil-to-lymphocyte (NLR), derived-NRL (d-NLR), platelet-to-lymphocyte (PLR), and lymphocyte-to-C-reactive protein (LCR) ratios in predicting the progression to septic shock and death. Materials and Methods: A retrospective analysis of a consecutive series of ninety COVID-19 patients with prolonged hospitalization (exceeding 15 days) admitted to the ICU was conducted. The prevalence of culture-proven HAIs throughout their hospital stays was documented. NLR, dNLR, PLR, and LCR were recorded on admission, day 7, and day 14 to assess their discriminative prowess for detecting further progression to septic shock or death. Results: The prevalence of HAIs was 76.6%, 50% of patients met the criteria for septic shock, and 50% died. The median time to the first positive culture was 13.5 days and 20.5 days for developing septic shock. Mechanical ventilation was a key contributing factor to HAI, septic shock, and mortality. On admission and day 7 NLR, dNLR, PLR, and LCR values had no prognostic relevance for events occurring late during hospitalization. However, day-14 NLR, dNLR, and PLR were independent predictors for progression to septic shock and mortality and have shown good discriminative capabilities. The AUCs for septic shock were 0.762, 0.764, and 0.716, while the values for predicting in-hospital death were 0.782, 0.778, and 0.758, respectively. Conclusions: NLR, dNLR, and PLR are quick, easy-to-use, cheap, effective biomarkers for the detection of a more severe disease course, of the late development of HAIs, and of the risk of death in critically ill patients requiring a prolonged ICU stay