Treatment Decision-Making of Secondary Prevention After Venous Thromboembolism: Data From the Real-Life START2-POST-VTE Register

Patients with venous thromboembolism (VTE) should receive a decision on the duration of anticoagulant treatment (AT) that is often not easy to make. Sixteen Italian clinical centers included patients with recent VTE in the START2-POST-VTE register and reported the decisions taken on duration of AT in each patient and the reasons for them. At the moment of this report, 472 (66.9%) of the 705 patients included in the registry were told to stop AT in 59.3% and to extend it in 40.7% of patients. Anticoagulant treatment lasted 653 months in >90% of patients and was extended in patients with proximal deep vein thrombosis because considered at high risk of recurrence or had thrombophilic abnormalities. d-dimer testing, assessment of residual thrombus, and patient preference were also indicated among the criteria influencing the decision. In conclusion, Italian doctors stuck to the minimum 3 months AT after VTE, while the secondary or unprovoked nature of the event was not seen as the prevalent factor influencing AT duration which instead was the result of a complex and multifactorial evaluation of each patient

Low in‑hospital mortality rate in patients with COVID‑19 receiving thromboprophylaxis: data from the multicentre observational START‑COVID Register

Abstract COVID-19 infection causes respiratory pathology with severe interstitial pneumonia and extra-pulmonary complications; in particular, it may predispose to thromboembolic disease. The current guidelines recommend the use of thromboprophylaxis in patients with COVID-19, however, the optimal heparin dosage treatment is not well-established. We conducted a multicentre, Italian, retrospective, observational study on COVID-19 patients admitted to ordinary wards, to describe clinical characteristic of patients at admission, bleeding and thrombotic events occurring during hospital stay. The strategies used for thromboprophylaxis and its role on patient outcome were, also, described. 1091 patients hospitalized were included in the START-COVID-19 Register. During hospital stay, 769 (70.7%) patients were treated with antithrombotic drugs: low molecular weight heparin (the great majority enoxaparin), fondaparinux, or unfractioned heparin. These patients were more frequently affected by comorbidities, such as hypertension, atrial fibrillation, previous thromboembolism, neurological disease,and cancer with respect to patients who did not receive thromboprophylaxis. During hospital stay, 1.2% patients had a major bleeding event. All patients were treated with antithrombotic drugs; 5.4%, had venous thromboembolism [30.5% deep vein thrombosis (DVT), 66.1% pulmonary embolism (PE), and 3.4% patients had DVT + PE]. In our cohort the mortality rate was 18.3%. Heparin use was independently associated with survival in patients aged ≥ 59 years at multivariable analysis. We confirmed the high mortality rate of COVID-19 in hospitalized patients in ordinary wards. Treatment with antithrombotic drugs is significantly associated with a reduction of mortality rates especially in patients older than 59 years

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Too many dangerous allergies

Mastocytosis is a rare clonal disease characterized by an abnormal proliferation of mast cells, which accumulate in one or several organ systems such as skin, bone marrow, liver, spleen, lymph nodes and gastrointestinal tract. The heterogeneity of the clinical presentation is typically related to different disease burdens in various tissues and symptoms due to the release of mast cell mediators. The diagnosis is often difficult and delayed. Here we describe the case of a 70-year old patient with a past history of drug-induced anaphylactic shock whose clinical presentation was dramatic and required intensive support: the diagnosis of systemic mastocytosis was reached after the exclusion of diseases more commonly encountered in routine clinical practice (e.g. stroke, pulmonary embolism)

Long-Term Outcomes in Two-Year Follow-Up after Primary Treatment in Patients with a Prior Venous Thromboembolic Event: A Prospective, Observational, Real-Life Study

Background: Patients with acute venous thromboembolism (VTE) need anticoagulation (AC) therapy for at least 3/6 months (primary treatment); after that period, they should receive a decision on the duration of therapy. Methods: This study examined the complications occurring during two years of follow-up (FU) in patients with a first VTE who were recruited in 20 clinical centers and had discontinued or prolonged AC. They were included in the START2-POST-VTE prospective observational study. Results: A total of 720 patients (53.5% males) who, after the completion of primary treatment, had received the decision to continue (n = 281, 39%; 76.1% with a DOAC) or discontinue (n = 439, 61%) AC were followed up for 2 years (total FU = 1318 years). The decision to prolong or suspend AC was made in similar proportions in patients with unprovoked or provoked index events. Courses of sulodexide treatment or Aspirin (100 mg daily) were prescribed to 20.3% and 4.5%, respectively, of the patients who discontinued AC. The bleeding rate was significantly higher in patients who extended AC (1.6% pt/y) than in those who stopped AC (0.1% pt/y; p = 0.001) and was higher in patients using standard-dose DOACs (3.1% pt/y) than in those using reduced-dose DOACs (0.4% pt/y). The recurrent VTE rates were similar between the two groups (2.2% pt/y during AC vs. 3% pt/y off AC). Conclusion: Physicians’ decisions about AC duration were independent of the unprovoked/provoked nature of the index event. The bleeding rate was higher in patients who continued AC using standard-dose DOACs. Surprisingly, the rate of thrombotic recurrence was not different between those who continued or discontinued AC. Randomized studies comparing different procedures to decide on the duration of AC after a first VTE are needed

Venous thromboembolism secondary to hospitalization for COVID-19: patient management and long-term outcomes

Background: Venous thromboembolism (VTE) is a complication of COVID-19 in hospitalized patients. Little information is available on long-term outcomes of VTE in this population.Objectives: We aimed to compare the characteristics, management strategies, and long-term clinical outcomes between patients with COVID-19-associated VTE and patients with VTE provoked by hospitalization for other acute medical illnesses.Methods: This is an observational cohort study, with a prospective cohort of 278 patients with COVID-19-associated VTE enrolled between 2020 and 2021 and a comparison cohort of 300 patients without COVID-19 enrolled in the ongoing START2-Register between 2018 and 2020. Exclusion criteria included age <18 years, other indications to anticoagulant treatment, active cancer, recent (<3 months) major surgery, trauma, pregnancy, and participation in interventional studies. All patients were followed up for a minimum of 12 months after treatment discontinuation. Primary end point was the occurrence of venous and arterial thrombotic events.Results: Patients with VTE secondary to COVID-19 had more frequent pulmonary embolism without deep vein thrombosis than controls (83.1% vs 46.2%, P <.001), lower prevalence of chronic inflammatory disease (1.4% and 16.3%, P <.001), and history of VTE (5.0% and 19.0%, P <.001). The median duration of anticoagulant treatment (194 and 225 days, P = 0.9) and the proportion of patients who discontinued anticoagulation (78.0% and 75.0%, P = 0.4) were similar between the 2 groups. Thrombotic event rates after discontinuation were 1.5 and 2.6 per 100 patient-years, respectively (P = 0.4). Conclusion: The risk of recurrent thrombotic events in patients with COVID-19- associated VTE is low and similar to the risk observed in patients with VTE secondary to hospitalization for other medical diseases

Genetically-driven CD39 expression shapes human tumor-infiltrating CD8+ T cell functions

In this study, we investigated the role of CD39 on tumor-infiltrating CD8+ T lymphocytes (CD8+ TILs) in colorectal, head and neck and pancreatic cancers. Partially confirming recent observations correlating the CD39 expression with T cell exhaustion, we demonstrated a divergent functional activity in CD39+CD8+ TILs. On the one hand, CD39+CD8+ TILs (as compared with their CD39– counterparts) produced significantly lower IFN- and IL-2 amounts, expressed higher PD-1, and inversely correlated with perforin and granzyme B expression. On the other, they displayed a significantly higher proliferative capacity ex vivo that was inversely correlated with the PD-1 expression. Therefore, CD39+CD8+ TILs, including those co-expressing the CD103 (a marker of T resident memory [TRM] cells), were defined as partially dysfunctional T cells that correlate with tumor patients with initial progression stages. Interestingly, our results identified for the first time a single nucleotide polymorphism (SNP rs10748643 A > G), as a genetic factor associated with CD39 expression in CD8+ TILs. Finally, we demonstrated that compounds inhibiting CD39-related ATPases improved CD39+CD8+ T cell effector function ex vivo, and that CD39+CD8+ TILs displayed effective suppression function in vitro. Overall these data suggest that the SNP analysis may represent a suitable predictor of CD39+CD8+ T cell expression in cancer patients, and propose the modulation of CD39 as a new strategy to restore partially exhausted CD8+ TILs