How Many Times Can One Go Back to the Drawing Board before the Accurate Diagnosis and Surgical Treatment of Glucagonoma?

Glucagonomas are neuroendocrine tumors (NETs) that arise from the alpha cells of the pancreatic islets. They are typically slow-growing tumors associated with abnormal glucagon secretion, resulting in one or more non-specific clinical features, such as necrolytic migratory erythema (NME), diabetes, diarrhea, deep vein thrombosis, weight loss, and depression. Here, we report the case of a 44-year-old male with a history of diabetes mellitus, presenting with a pruritic and painful disseminated cutaneous eruption of erythematous plaques, with scales and peripheral pustules, misdiagnosed as disseminated pustular psoriasis and treated for 2 years with oral retinoid and glucocorticoids. During this period, the patient complained of weight loss of 32 kg and diarrhea and developed deep vein thrombosis. These symptoms, together with an inadequate response to therapy of the skin lesions, led to the reassessment of the initial diagnosis. Laboratory tests confirmed elevated plasma glucagon levels (>1000 pg/mL) and computed tomography (CT) scans revealed a 35/44 mm tumor in the pancreatic tail. Due to considerable disease complications and the COVID-19 pandemic, the surgical removal of the tumor was delayed for nearly 2 years. During this time, somatostatin analogue therapy efficiently controlled the glucagonoma syndrome and likely prevented tumor progression. As in other functional pancreatic NETs, the early clinical recognition of hormonal hypersecretion syndrome and the multidisciplinary approach are the keys for best patient management.

Comparison of deep vein thrombosis risks in acute respiratory distress syndrome Caused by COVID-19 and Bacterial Pneumonia: A Retrospective Cohort Study

Background: High incidence of deep vein thrombosis (DVT) has been observed in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 and those by bacterial pneumonia. However, it is also important to differentiate between these two groups of patients. Study Design and Methods: We performed a retrospective cohort study to investigate the difference of DVT between the two independent cohorts of ARDS and eventually enrolled 240 patients, 105 of whom with ARDS caused by COVID-19 and 135 by bacterial pneumonia. We analyzed demographics and clinical characteristics for patients with and without DVT in these two cohorts and explored the main differences and similarities between them.Results: The 28-days incidence of DVT in COVID-19 cohort was higher than that in bacterial pneumonia cohort (57.1% vs 41.5%, P=0.016). Taking death as competitive risk, Fine-Gray test showed no significant difference in 28-day cumulative incidence of DVT between these two groups (P=0.220). Fine-Gray competing risk analysis showed an association between CK (creatine kinase isoenzyme)-MB levels, PaO2 (partial pressure of arterial oxygen)/FiO2 (fraction of inspired oxygen) ratios, D-dimer levels and DVT in COVID-19 cohort and an association between serum creatinine levels, IMV, and DVT in bacterial pneumonia cohort. The sensitivity and specificity of corresponding receiver operating characteristic curve originating from the combination of CK-MB levels, PaO2/FiO2 ratios and D-dimer levels ≥ 0.5 µg/mL was not inferior to those of the Padua prediction score and the Wells score for screening for DVT in COVID-19 cohort.Conclusions: Compared with patients with ARDS caused by bacterial pneumonia, the incidence of DVT is higher by logistic model in patients with ARDS caused by COVID-19, and the risk factors for DVT are completely different. Our novel prediction model can aid early identifying patients with high risk for DVT.

Development and validation of a prediction model to estimate risk of acute pulmonary embolism in deep vein thrombosis patients

Venous thromboembolism (VTE), clinically presenting as deep vein thrombosis (DVT) or pulmonary embolism (PE). Not all DVT patients carry the same risk of developing acute pulmonary embolism (APE). To develop and validate a prediction model to estimate risk of APE in DVT patients combined with past medical history, clinical symptoms, physical signs, and the sign of the electrocardiogram. We analyzed data from a retrospective cohort of patients who were diagnosed as symptomatic VTE from 2013 to 2018 (n = 1582). Among them, 122 patients were excluded. All enrolled patients confirmed by pulmonary angiography or computed tomography pulmonary angiography (CTPA) and compression venous ultrasonography. Using the LASSO and logistics regression, we derived a predictive model with 16 candidate variables to predict the risk of APE and completed internal validation. Overall, 52.9% patients had DVT + APE (773 vs 1460), 47.1% patients only had DVT (687 vs 1460). The APE risk prediction model included one pre-existing disease or condition (respiratory failure), one risk factors (infection), three symptoms (dyspnea, hemoptysis and syncope), five signs (skin cold clammy, tachycardia, diminished respiration, pulmonary rales and accentuation/splitting of P2), and six ECG indicators (SIQIIITIII, right axis deviation, left axis deviation, S1S2S3, T wave inversion and Q/q wave), of which all were positively associated with APE. The ROC curves of the model showed AUC of 0.79 (95% CI, 0.77–0.82) and 0.80 (95% CI, 0.76–0.84) in the training set and testing set. The model showed good predictive accuracy (calibration slope, 0.83 and Brier score, 0.18). Based on a retrospective single-center population study, we developed a novel prediction model to identify patients with different risks for APE in DVT patients, which may be useful for quickly estimating the probability of APE before obtaining definitive test results and speeding up emergency management processes.

Comparative Study of Deep Vein Thrombosis Recanalization Using Doppler Ultrasound in Different Post-Treatment Intervals in Traumatic Patients

Deep vein thrombosis (DVT) is a prevalent vascular disease characterized by pelvic and limb deep vein thrombophlebitis, and it has a high incidence in traumatic patients. Contrary to older studies, recent research has reported that recanalization in DVT is not a slow process. The present study aimed at the comparative examination of DVT recanalization with Doppler ultrasound in different intervals following treatment with heparin or enoxaparin. This prospective study was conducted on all traumatic patients hospitalized in Imam Reza Hospital of Kermanshah, Iran, with the clinical and sonographic diagnosis of DVT in limb veins. Doppler ultrasound was performed two weeks, one month, and three months following treatment in order to examine recanalization. Data were analyzed using statistical tests in SPSS16 at the significance level of <0.05. Based on Doppler ultrasound, a significant difference was found between the degree of recanalization in patients aged <45 years and those aged >45 years, between male and female patients, and between different DVT locations (P<0.05). After three months of treatment with heparin and enoxaparin, the degree of recanalization was increased in DVT. Moreover, it was found that Doppler ultrasound is a useful tool for the diagnosis of recanalization in patients with DVT.

What We Know (and Do not Know) Regarding the Pathogenesis of Pulmonary Thrombosis in COVID-19

The clinical course of coronavirus disease 2019 (COVID-19) is often complicated by the onset of venous thrombosis and thromboembolism (VTE), encompassing also pulmonary thrombosis. Recent statistics attests that the cumulative frequency of VTE can be as high as 30% in COVID-19 hospitalized patients, increasing to nearly 40 to 70% (depending on systematic screening) in those with severe illness, mechanical ventilation, or intensive care unit admission. The risk of venous thrombosis seems mostly limited to the active phase of disease, and is directly associated with some genetic (i.e., inherited prothrombotic predisposition) and demographical factors (male sex, overweight/obesity), disease severity (risk increasing progressively from hospitalization to development of severe illness, being the highest in patients needing mechanical ventilation and/or intensive care), presence and extent of pulmonary disease, coexistence of multiple risk factors (immobilization, mechanical ventilation, co- or superinfections), along with increased values of inflammatory and thrombotic biomarkers. At least three different phenotypes of pulmonary thrombosis may develop in COVID-19 patients, one caused by typical embolization from peripheral venous thrombosis (e.g., deep vein thrombosis), a second type triggered by local inflammation of nearby pulmonary tissue, and a third one mostly attributable to the prothrombotic state consequent to the pronounced systemic inflammatory response (i.e., the so-called cytokine storm) that is frequently observed in COVID-19. Although the pathogenesis of these three conditions has different features, their discrimination is essential for diagnostic and therapeutic purposes. The prognosis of COVID-19 patients who develop pulmonary thrombosis is also considerably worse than those who do not, thus probably needing frequent monitoring and more aggressive therapeutic management.

Upper extremity deep vein thrombosis in COVID-19: Incidence and correlated risk factors in a cohort of non-ICU patients

Background Venous thromboembolism is a frequent complication of COVID-19 infection. Less than 50% of pulmonary embolism (PE) is associated with the evidence of deep venous thrombosis (DVT) of the lower extremities. DVT may also occur in the venous system of the upper limbs especially if provoking conditions are present such as continuous positive airway pressure (CPAP). The aim of this study was to evaluate the incidence of UEDVT in patients affected by moderate-severe COVID-19 infection and to identify potential associated risk factors for its occurrence. Methods We performed a retrospective analysis of all patients affected by moderate-severe COVID-19 infection admitted to our unit. In accordance with the local protocol, all patients had undergone a systematic screening for the diagnosis of UEDVT, by vein compression ultrasonography (CUS). All the patients were receiving pharmacological thromboprophylaxis according to international guidelines recommendations. Univariate and multivariate analyses were used to identify risk factors associated with UEDVT. Results 257 patients were included in the study, 28 patients were affected by UEDVT with an incidence of 10.9% (95% CI, 7.1–14.7). At univariate analysis UEDVT appeared to be significantly associated (p< 0.05) with pneumonia, ARDS, PaO2/FiO2, D-dimer value higher than the age adjusted cut off value and need for CPAP ventilation. Multivariate analysis showed a significant association between UEDVT and the need for CPAP ventilation (OR 5.95; 95% IC 1.33–26.58). Increased mortality was found in patients affected by UEDVT compared to those who were not (OR 3.71; 95% CI, 1.41–9.78). Conclusions UEDVT can occur in COVID-19 patients despite adequate prophylaxis especially in patients undergoing helmet CPAP ventilation. Further studies are needed to identify the correct strategy to prevent DVT in these patients.

D-dimer level significance for deep vein thrombosis screening in the third trimester: a retrospective study

Background Venous thromboembolism often develops after surgery and childbirth, resulting in death in some cases. Although early deep vein thrombosis (DVT) detection can predict pulmonary thromboembolism, there is no early screening method for DVT in pregnant women. Lack of consensus regarding significance or setting and cut-off value interpretation of D-dimer levels further impedes venous thromboembolism screening in pregnant women. This study aimed to examine the utility of third-trimester serum D-dimer levels as a screening test for DVT during pregnancy and to determine the frequency of asymptomatic DVT using lower-limb compression ultrasonography. Methods This single-center retrospective study included 497 pregnant women who underwent elective cesarean section at term in our hospital between January 2013 and December 2019. Serum D-dimer levels were preoperatively measured at 32–37 weeks’ gestation. The presence or absence of DVT in patients with serum D-dimer levels ≥ 3.0 µg/ml, the cut-off value, was examined using compression ultrasonography. In all patients, the presence or absence of clinical venous thrombosis (symptoms such as lower-limb pain, swelling, and heat sensation) was examined within 4 postoperative weeks. The Royal College of Obstetricians and Gynecologists Guideline 2015 was referred to determine risk factors for the onset of venous thrombosis during pregnancy. Among those, we examined the risk factors for DVT that result in high D-dimer levels during pregnancy. Results The median age and body mass index were 35 (20–47) years and 21.2 (16.4–41.1) kg/m2, respectively. Further, the median gestational age and D-dimer levels were 37 weeks and 2.1 (0.2–16.0) µg/ml, respectively. Compression ultrasonography was performed on 135 (26.5%) patients with a D-dimer level ≥ 3.0 µg/ml, with none of the patients showing DVT. All patients were followed up for 4 postoperative weeks, with none presenting with venous thromboembolism. Multivariate analysis showed that hypertensive disorders of pregnancy are an independent risk factor for venous thromboembolism that causes high D-dimer levels (odds ratio: 2.48, 95% confidence interval: 1.05–6.50, P = 0.04). Conclusion There may be low utility in screening for DVT using D-dimer levels in the third trimester. Further, prepartum asymptomatic DVT has a low frequency, indicating the low utility of compression ultrasonography. Trial registration Institutional Review Board of Tottori University Hospital (IRB no. 20A149).

Risk Factors for Post-Thrombotic Syndrome in Patients With a First Proximal Deep Venous Thrombosis Treated With Direct Oral Anticoagulants

The incidence of post-thrombotic syndrome (PTS) in patients with deep vein thrombosis (DVT) treated with direct oral anticoagulants (DOACs) remains a matter of debate. Hence, our endeavor to investigate a large cohort of patients with a first episode of proximal DVT treated with DOACs to ascertain the incidence and predisposing risk factors for PTS. All consecutive patients referred to the Thrombotic and Haemorrhagic Diseases Unit of Padova University Hospital (Italy) between January 2014 and January 2018 for a first episode of proximal DVT were considered for enrollment. Participants received DOACs for a minimum period of 3 months. PTS was assessed using the Villalta score up to 36 months after DVT diagnosis. Among 769 enrolled patients (M/F 353/416, age range 26–87 years), 152 (19.8%) developed PTS and 30 (3.9%) developed severe PTS. The adjusted hazard ratio was significant for obesity (1.64, 95% CI 1.28–2.39) and DVT site (femoral and/or iliac veins vs popliteal vein) (1.23, 95% CI 1.15–3.00). The incidence of PTS is not negligible in patients with proximal DVT despite the use of DOACs. We identified obesity and iliofemoral DVT as possible risk factors for PTS. Larger prospective studies are needed to confirm our findings and optimize therapeutic strategies.

A Popliteal Vein Aneurysm Accompanied by Lower Persistent Sciatic Vein

Popliteal venous aneurysms (PVAs) are rare. Surgical treatment is recommended because of the risk of deep vein thrombosis and fatal pulmonary embolism. A persistent sciatic vein (PSV) is also a rare anomaly. We report a case of a PVA accompanied by a lower PSV. A 70-year-old man was admitted due to left leg heaviness. He had undergone ablation of both great saphenous veins 6 years prior to the admission. Duplex ultrasound showed a PVA on his left leg, which was 3.2 × 2.4 cm in size. The patient was treated with tangential aneurysmectomy with lateral venorrhaphy. His symptom gradually resolved. He received warfarin at a therapeutic range for 3 months. Duplex ultrasound at 6 months later showed no evidence of any recurrent aneurysm or venous reflux. His follow-up has revealed no complications for 18 months. Surgical treatment and perioperative therapeutic anticoagulation are recommended for treating PVAs. Tangential aneurysmectomy with venorrhaphy is the most common and the simplest surgical method.