Congenital agenesis of the inferior vena cava (AIVC) is a rare vascular abnormality with a prevalence of 0.0005 to 1% in the general population. This condition is found in almost 5% of young patients (younger than 30 years) with proximal, typically bilateral, deep venous thrombosis (DVT) of the lower limbs, often in the absence of apparent risk factors. However, AIVC in young patients with DVT is probably underestimated because AIVC cannot be detected by the standard DVT diagnostic workup. Inherited thrombophilia has been reported in patients with AIVC-associated DVT, as an additional risk factor, but its role is poorly investigated. The best therapeutic strategy and the optimal duration of anticoagulant treatment of DVT in patients with AIVC are still unclear. Here, we describe 14 young patients (2 females and 12 males, mean age at first DVT: 27.8 ± 10.1 years), with color Doppler ultrasound (US) and abdominal computed tomography scan confirmed AIVC-associated DVT and discuss their characteristics in the framework of a literature review on this topic. Our patients were mainly males (10/12) and experienced proximal DVT events, not complicated by pulmonary embolism. DVT-precipitating factors were detected only in five cases, the two female patients (oral contraceptives and puerperium), and three male patients (one after leg fracture and two after abdominal surgery). Thrombophilic abnormalities were found in eight patients (heterozygous factor V Leiden mutation, n = 3; mild/moderate hyperhomocysteinemia, n = 3; reduced protein C activity, n = 1; antiphospholipid syndrome, n = 1). The majority of patients (13/14) were treated with long-term oral anticoagulant therapy and elastic stockings (ES), with a very low rate of DVT recurrence (1/14, mean follow-up 7 years). These clinical characteristics were largely consistent with those of 161 patients identified by review of the literature. On the whole, although many aspects are still poorly known, our case series and literature review suggest that a search should be undertaken for AIVC in young patients with proximal idiopathic, particularly when bilateral, DVT, which should then be treated with prolonged anticoagulation and ES.

To test the prognostic performance of different scores, both specifically designed for patients with COVID-19 and generic, in predicting in-hospital mortality and the need for mechanical ventilation (MV). We retrospectively collected clinical data of patients admitted to the Emergency Department of the University Hospital AOU Careggi, Florence, Italy, between February 2020 and January 2021, with a confirmed infection by SARS-CoV2. We calculated the following scores: Sequential Organ Failure Assessment (SOFA) score, CALL score, 4C Mortality score, QUICK score, CURB-65 and MuLBSTA score. The end-points were in-hospital mortality and the need for MV. We included 1208 patients, mean age 60 ± 17 years, 57% male sex. Compared to survivors, non-survivors showed significantly higher values of all the prognostic scores (4C: 13 [10–15] vs 8 [4–10]; CALL: 11 [10–12] vs 9 [7–11]; QUICK: 4 [1–6] vs 0 [0–3]; SOFA: 5 [4–6] vs 4 [4–5]; CURB: 2 [1–3] vs 1 [0–1]; MuLBSTA: 11 [9–13] vs 9 [7–11], all p < 0.001). Discriminative ability evaluated by the Receiver Operating Curve analysis showed the following values of the Area under the Curve: 0.83 for 4C, 0.74 for CALL, 0.70 for QUICK, 0.68 for SOFA, 0.76 for CURB and 0.64 for MuLBSTA. The mortality rate significantly increased in increasing quartiles of 4C and CALL score (respectively, 2, 8, 24 and 54% for the 4C score and 1, 17, 33 and 68% for the CALL score, both p < 0.001). 4C and CALL score allowed an early and good prognostic stratification of patients admitted for pneumonia induced by SARS-CoV2.

Warfarin is an oral anticoagulant, commonly used for primary and secondary prevention of venous and arterial thromboembolic events. The drug is characterized by narrow therapeutic index, widespread individual variability in clinical response, and high rates of adverse events, particularly bleeding complications. For these reasons, a close monitoring of the dosage, using the frequent assessment of coagulation status by means of International Normalized Ratio value, is mandatory. Warfarin is metabolized by hepatic cytochrome P-450. High CYP 450 activity may lead to low drug concentration and requires high warfarin doses to reach efficacy; conversely, low CYP 450 activity is responsible for high drug concentration and needs for low doses to avoid potential toxicity risks. The major isoforms of CYP involved in the metabolism of warfarin sodium are CYP1A2 (for the R-warfarin) and CYP2C9 (for the S-warfarin). The probes for testing CYP1A2 are phenacetin and caffeine while for CYP2C9 tolbutamide. Although S-warfarin has major activity, it was decided to exclude its phenotyping for ethical issues, being mandatory to use a drug (tolbutamide). Instead, it was chosen to test the 1A2 isoform, as the activity of the latter isoform could be investigated by using caffeine contained in the caffeinated beverages. Specifically, a single-point concentration of salivary caffeine (total overnight salivary caffeine assessment [TOSCA]) after an overnight period of the caffeinated beverages abstinence was utilized. In the present study, 75 nonsmoker patients regularly receiving warfarin sodium were enrolled. The results have showed a significant association of the warfarin dose with TOSCA values (coefficient = -0.15, standard error = 0.04, 95% confidence interval = -0.24 to -0.06, t = -3.23, P = .002). In conclusion, the phenotyping of CYP1A2 by TOSCA could be useful, if further proven, to help manage patients on warfarin in order to lessen severe adverse events.

Hypogammaglobulinemia is associated with increased 1-year mortality in chronic obstructive pulmonary disease [abstract].

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