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.

Transarterial Radioembolization for Unresectable Hepatocellular Carcinoma: Real-Life Efficacy and Safety Analysis of Korean Patients

Transarterial radioembolization (TARE) has become widely used in the treatment of HCC, one of the most common causes of cancer mortality worldwide. Here we investigated the long-term clinical outcomes of patients with hepatocellular carcinoma (HCC) treated with TARE in a multi-medical center in Korea. A total of 149 patients treated with TARE from 2008–2014 were recruited. The pre-treatment HCC stage was classified according to the BCLC stage, of which C and D were defined as advanced HCC. Advanced HCC stage and Child–Turcotte–Pugh (CTP) score A were identified in 62 (42%) and 134 (90%) patients, respectively. Portal vein thrombosis (PVT) was identified in 58 patients (38.9%). The median time to progression (TTP) was 14 months, and the median overall survival (OS) and progression-free survival (PFS) were 18.6 and 8.9 months, respectively. The overall tumor response was 47%, and the disease control rate was 78%. OS and PFS differed significantly according to the presence of liver cirrhosis, extrahepatic metastasis, tumor response and curative treatment after TARE (all, p < 0.05). Multiple tumors and major PVT were other independent factors related to OS, while the des-gamma carboxy protein level predicted PFS (all, p < 0.05). Tumor size was an independent predictor of tumor response. TTP, OS and PFS all differed among BCLC stages. The serious adverse effect after TARE was clinically not significant. Therefore, TARE is safe and effective in treating early to advanced HCCs.

Recent Developments in Clinical Plasma Proteomics—Applied to Cardiovascular Research

The human plasma proteome mirrors the physiological state of the cardiovascular system, a fact that has been used to analyze plasma biomarkers in routine analysis for the diagnosis and monitoring of cardiovascular diseases for decades. These biomarkers address, however, only a very limited subset of cardiovascular diseases, such as acute myocardial infarct or acute deep vein thrombosis, and clinical plasma biomarkers for the diagnosis and stratification cardiovascular diseases that are growing in incidence, such as heart failure and abdominal aortic aneurysm, do not exist and are urgently needed. The discovery of novel biomarkers in plasma has been hindered by the complexity of the human plasma proteome that again transforms into an extreme analytical complexity when it comes to the discovery of novel plasma biomarkers. This complexity is, however, addressed by recent achievements in technologies for analyzing the human plasma proteome, thereby facilitating the possibility for novel biomarker discoveries. The aims of this article is to provide an overview of the recent achievements in technologies for proteomic analysis of the human plasma proteome and their applications in cardiovascular medicine.

COVID-19 is associated with higher risk of venous thrombosis, but not arterial thrombosis, compared with influenza: Insights from a large US cohort

Introduction Infection with SARS-CoV-2 is typically compared with influenza to contextualize its health risks. SARS-CoV-2 has been linked with coagulation disturbances including arterial thrombosis, leading to considerable interest in antithrombotic therapy for Coronavirus Disease 2019 (COVID-19). However, the independent thromboembolic risk of SARS-CoV-2 infection compared with influenza remains incompletely understood. We evaluated the adjusted risks of thromboembolic events after a diagnosis of COVID-19 compared with influenza in a large retrospective cohort. Methods We used a US-based electronic health record (EHR) dataset linked with insurance claims to identify adults diagnosed with COVID-19 between April 1, 2020 and October 31, 2020. We identified influenza patients diagnosed between October 1, 2018 and April 31, 2019. Primary outcomes [venous composite of pulmonary embolism (PE) and acute deep vein thrombosis (DVT); arterial composite of ischemic stroke and myocardial infarction (MI)] and secondary outcomes were assessed 90 days post-diagnosis. Propensity scores (PS) were calculated using demographic, clinical, and medication variables. PS-adjusted hazard ratios (HRs) were calculated using Cox proportional hazards regression. Results There were 417,975 COVID-19 patients (median age 57y, 61% women), and 345,934 influenza patients (median age 47y, 66% women). Compared with influenza, patients with COVID-19 had higher venous thromboembolic risk (HR 1.53, 95% CI 1.38–1.70), but not arterial thromboembolic risk (HR 1.02, 95% CI 0.95–1.10). Secondary analyses demonstrated similar risk for ischemic stroke (HR 1.11, 95% CI 0.98–1.25) and MI (HR 0.93, 95% CI 0.85–1.03) and higher risk for DVT (HR 1.36, 95% CI 1.19–1.56) and PE (HR 1.82, 95% CI 1.57–2.10) in patients with COVID-19. Conclusion In a large retrospective US cohort, COVID-19 was independently associated with higher 90-day risk for venous thrombosis, but not arterial thrombosis, as compared with influenza. These findings may inform crucial knowledge gaps regarding the specific thromboembolic risks of COVID-19.

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.

Interventional recanalization therapy in patients with non-cirrhotic, non-malignant portal vein thrombosis: comparison between transjugular versus transhepatic access

Purpose To compare the safety and outcome of transjugular versus percutaneous technique in recanalization of non-cirrhotic, non-malignant portal vein thrombosis. Methods We present a retrospective bicentric analysis of 21 patients with non-cirrhotic, non-malignant PVT, who were treated between 2016 and 2021 by interventional recanalization via different access routes (percutaneous [PT] vs. transjugular in transhepatic portosystemic shunt [TIPS] technique). Complication rates with a focus on periprocedural bleeding and patency as well as outcome were compared. Results Of the 21 patients treated (median age 48 years, range of 19–78), seven (33%) patients had an underlying prothrombotic condition. While 14 (57%) patients were treated for acute PVT, seven (43%) patients had progressive thrombosis with known chronic PVT. Nine patients underwent initial recanalization via PT access and twelve via TIPS technique. There was no significant difference in complete technical success rate according to initial access route (55.5% in PT group vs. 83.3% in TIPS group, p = 0.331). However, creation of an actual TIPS was associated with higher technical success in restoring portal venous flow (86.6% vs. 33.3%, p = 0.030). 13 (61.9%) patients received thrombolysis. Nine (42.8%) patients experienced hemorrhagic complications. In a multivariate analysis, thrombolysis (p = 0.049) and PT access as the first procedure (p = 0.045) were significant risk factors for bleeding. Conclusion Invasive recanalization of the portal vein in patients with PVT and absence of cirrhosis and malignancy offers a good therapeutic option with high recanalization and patency rates. Bleeding complications result predominantly from a percutaneous access and high amounts of thrombolytics used; therefore, recanalization via TIPS technique should be favored.