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.

(More than) doubling down: Effective fibrinolysis at a reduced rt-PA dose for catheter-directed thrombolysis combined with histotripsy

Deep vein thrombosis is a major source of morbidity and mortality worldwide. For acute proximal deep vein thrombosis, catheter-directed thrombolytic therapy is an accepted method for vessel recanalization. Thrombolytic therapy is not without risk, including the potential for hemorrhagic bleeding that increases with lytic dose. Histotripsy is a focused ultrasound therapy that generates bubble clouds spontaneously in tissue at depth. The mechanical activity of histotripsy increases the efficacy of thrombolytic therapy at doses consistent with current pharmacomechanical treatments for venous thrombosis. The objective of this study was to determine the influence of lytic dose on histotripsy-enhanced fibrinolysis. Human whole blood clots formed in vitro were exposed to histotripsy and a thrombolytic agent (recombinant tissue plasminogen activator, rt-PA) in a venous flow model perfused with plasma. Lytic was administered into the clot via an infusion catheter at concentrations ranging from 0 (control) to 4.54 μg/mL (a common clinical dose for catheter-directed thrombolysis). Following treatment, perfusate samples were assayed for markers of fibrinolysis, hemolysis, and intact red blood cells and platelets. Fibrinolysis was equivalent between the common clinical dose of rt-PA (4.54 μg/mL) and rt-PA at a reduction to one-twentieth of the common clinical dose (0.23 μg/mL) when combined with histotripsy. Minimal changes were observed in hemolysis for treatment arms with or without histotripsy, potentially due to clot damage from insertion of the infusion catheter. Likewise, histotripsy did not increase the concentration of red blood cells or platelets in the perfusate following treatment compared to rt-PA alone. At the highest lytic dose, a refined histotripsy exposure scheme was implemented to cover larger areas of the clot. The updated exposure scheme improved clot mass loss and fibrinolysis relative to administration of lytic alone. Overall, the data collected in this study indicate the rt-PA dose can be reduced by more than a factor of ten and still promote fibrinolysis when combined with histotripsy.

The Outcome of Catheter-Directed Thrombolysis in COVID-19-Associated Deep Vein Thrombosis

Introduction Published evidence of venous thrombotic complications of COVID-19 is lacking from India. This case series consists of twenty-nine adult patients who were COVID -19 positive and treated for Deep Vein Thrombosis (DVT) during the second wave of the COVID-19 pandemic, in India. The study was aimed at analyzing patient demographics of patients with DVT and the outcome of Catheter-Directed Thrombolysis (CDT) in COVID positive patients. Material and Methods: Patients who developed DVT while or after being COVID positive were managed between February and April 2021 at the institution of the first two authors and were included in this retrospective study. Demographic, clinical data, laboratory data, and treatment given were analyzed. All patients were followed up for 3 months with a Villalta score. Results: There were a total of 29 patients (12 male and 17 female) included in the study with a mean age of 47 ± 17 years. The average time of presentation from being COVID positive was 17.8 ± 3.6 days and one patient developed DVT after becoming Covid negative. All but one patient had lower limb involvement, with 42.8% having proximal and 57.2% distal DVT. All patients with Iliofemoral and two with Femoropopliteal DVT were treated with catheter-di thrombolysis and the other 15 patients were managed with anticoagulation alone. No re-thrombosis was observed in the thrombolysis group. Overall average Villalta score at 3 months was 10.7 ± 2.1 with a score of 10.58 ± 2.1 in the anticoagulation-only group and 10.85 ± 2.3 in the CDT group. Conclusion: COVID-19 seems to be an additional risk factor in the development of DVT. The outcome of such patients, treated by thrombolysis appears to be similar to non-COVID patients. In this, observational experience of the authors suggests that CDT could be offered to COVID positive patients with symptomatic Iliofemoral DVT with good outcomes and an acceptable post-intervention Villalta score.

Complications of Stroke

Stroke is one of the leading causes of disability and mortality and can cause a serious socioeconomic burden. Some of the comorbidities and secondary complications of stroke can threaten the patient's life or cause serious pain or negatively affect the patient's involvement in rehabilitation or worsen daily life activities or make it difficult to bring the patient into the community and workplace. This chapter focuses on the symptoms and signs, diagnosis, and management of these comorbidities and complications. It highlights diagnosis and treatment of cardiac problems, sleep disorders, deep vein thrombosis, pulmonary embolism, dysphagia, malnutrition, and pneumonia. Depression, central post-stroke pain, upper limb problems after stroke, spasticity, bladder dysfunction are also discussed in this chapter.