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Int J Mol Sci ; 22(13)2021 Jul 01.
Article in English | MEDLINE | ID: covidwho-1295857


Hypercoagulation is one of the major risk factors for ICU treatment, mechanical ventilation, and death in critically ill patients infected with SARS-CoV-2. At the same time, hypoalbuminemia is one risk factor in such patients, independent of age and comorbidities. Especially in patients with severe SARS-CoV-2-infection, albumin infusion may be essential to improve hemodynamics and to reduce the plasma level of the main marker of thromboembolism, namely, the D-dimer plasma level, as suggested by a recent report. Albumin is responsible for 80% of the oncotic pressure in the vessels. This is necessary to keep enough water within the systemic circulatory system and for the maintenance of sufficient blood pressure, as well as for sufficient blood supply for vital organs like the brain, lungs, heart, and kidney. The liver reacts to a decrease in oncotic pressure with an increase in albumin synthesis. This is normally possible through the use of amino acids from the proteins introduced with the nutrients reaching the portal blood. If these are not sufficiently provided with the diet, amino acids are delivered to the liver from muscular proteins by systemic circulation. The liver is also the source of coagulation proteins, such as fibrinogen, fibronectin, and most of the v WF VIII, which are physiological components of the extracellular matrix of the vessel wall. While albumin is the main negative acute-phase protein, fibrinogen, fibronectin, and v WF VIII are positive acute-phase proteins. Acute illnesses cause the activation of defense mechanisms (acute-phase reaction) that may lead to an increase of fibrinolysis and an increase of plasma level of fibrinogen breakdown products, mainly fibrin and D-dimer. The measurement of the plasma level of the D-dimer has been used as a marker for venous thromboembolism, where a fourfold increase of the D-dimer plasma level was used as a negative prognostic marker in critically ill SARS-CoV-2 hospitalized patients. Increased fibrinolysis can take place in ischemic peripheral sites, where the mentioned coagulation proteins can become part of the provisional clot (e.g., in the lungs). Although critically ill SARS-CoV-2-infected patients are considered septic shock patients, albumin infusions have not been considered for hemodynamic resuscitation and as anticoagulants. The role of coagulation factors as provisional components of the extracellular matrix in case of generalized peripheral ischemia due to hypoalbuminemia and hypovolemia is discussed in this review.

Albumins/administration & dosage , COVID-19/therapy , Hemodilution/methods , Anticoagulants/administration & dosage , Blood Coagulation/drug effects , COVID-19/blood , COVID-19/metabolism , Critical Illness/therapy , Fibrinolysis/drug effects , Humans , SARS-CoV-2/isolation & purification , Thrombelastography
Tumori ; 107(6): NP24-NP27, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-992257


BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare tumor, accounting for about 1% of all pancreatic exocrine cancers. Consensus on the management of metastatic PACC remains unclear. CASE PRESENTATION: Starting from April 2019, a patient first received chemotherapy with two cycles of gemcitabine and nab-paclitaxel and two cycles of SOX regimen. After progression of disease evaluated based on RECIST 1.1, toripalimab and SOX regimen was administered because of PD-L1-positive expression, high tumor mutation burden (TMB), and somatic FANCA deletion in the tumor. Both the primary and metastatic tumor mass shrank significantly after two courses. The patient exhibited sustained partial response for at least six courses with well-controlled toxic effects. Then the treatment had to be stopped for 2 months because of the coronavirus disease 2019 pandemic. Computed tomography scan in March 2020 showed disease progression. Time from initiating treatment to tumor progression on toripalimab and SOX regimen treatment took up to at least 8 months. CONCLUSIONS: We present the first case report where a PD-L1 positive, high TMB, and FANCA-deleted pancreatic acinar cell carcinoma was treated using chemotherapy combined with immunotherapy, in which the patient exhibited satisfactory response and tolerance.

Antineoplastic Combined Chemotherapy Protocols/therapeutic use , B7-H1 Antigen/metabolism , Biomarkers, Tumor/genetics , Carcinoma, Acinar Cell/drug therapy , Immunotherapy/methods , Mutation , Pancreatic Neoplasms/drug therapy , Aged , Albumins/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Carcinoma, Acinar Cell/genetics , Carcinoma, Acinar Cell/immunology , Carcinoma, Acinar Cell/pathology , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Humans , Male , Paclitaxel/administration & dosage , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/immunology , Pancreatic Neoplasms/pathology