Updates in the diagnosis and management of chronic thromboembolic disease.

PURPOSE OF REVIEW: Chronic thromboembolic disease (CTED) is distinct from chronic thromboembolic pulmonary hypertension (CTEPH) and is defined by dyspnea on exertion after acute pulmonary embolism with the presence of residual perfusion defects and absence of resting pulmonary hypertension. Here, we review clinical features and diagnostic criteria for CTED and summarize treatment options. RECENT FINDINGS: The optimal management for CTED is unclear as the long-term outcomes of conservative vs. invasive treatment for this disease have not been reported. There are a few studies evaluating outcomes of pulmonary thromboendarterectomy and balloon pulmonary angioplasty (BPA) in CTED, concluding that these procedures are safe and effective in select patients. However, these trials are small nonrandomized observational studies, reporting outcomes only up to 1 year after the intervention. Conservative management of CTED with observation, pulmonary hypertension-targeted therapy, or cardiopulmonary rehabilitation has not been studied. It is unknown whether these treatments are as effective or superior to pulmonary thromboendarterectomy or BPA in CTED. SUMMARY: The management of CTED is individualized and based on symptoms and exercise limitations. Early referral of patients with CTED to a specialized CTEPH center is recommended to determine if watchful waiting, BPA, or pulmonary thromboendarterectomy is most beneficial.

Composite Angioimmunoblastic T-Cell Lymphoma and Diffuse Large B-Cell Lymphoma Presenting with Distributive Shock.

Diffuse large B-cell lymphoma (DLBCL) and angioimmunoblastic T-cell lymphoma (AITL) are two subtypes of non-Hodgkin lymphoma (NHL). The simultaneous occurrence of DLBCL and AITL in a composite lymphoma is very rare, and there are no established treatment regimens. We present the case of an 85-year-old male admitted to the intensive care unit with distributive shock, lymphocytosis, and lymphadenopathy, who was subsequently diagnosed with composite AITL and DLBCL, and treated with brentuximab vedotin (BV) and rituximab. To our knowledge, this is the first case of composite lymphoma presenting with distributive shock and treated with BV and rituximab, with successful resolution of shock.

Airway Hemorrhage Complicating Pulmonary Thromboendarterectomy: Risk Factors and Outcomes.

BACKGROUND: Airway hemorrhage is a known complication of pulmonary thromboendarterectomy (PTE) in patients with chronic thromboembolic pulmonary hypertension. Predisposing factors for postoperative airway hemorrhage have not been well described. The aims of this study were to determine the incidence and outcomes of airway hemorrhage after PTE and to identify potential risk factors. METHODS: This was a retrospective chart review of subjects undergoing PTE between 2015 and 2019. Postoperative airway hemorrhage was defined as significant endobronchial bleeding requiring withholding anticoagulation, bronchial blocker placement, and/or extracorporeal membrane oxygenation (ECMO). RESULTS: Of 877 subjects who underwent PTE, 58 subjects (6.6%) developed postoperative airway hemorrhage. Subjects with hemorrhage were more likely to be women (60% vs 45%, P = .03), to be older (57.8 vs 54.0 years, P = .04), and to have a higher incidence of preoperative hemoptysis (19.0% vs 7.6%, P = .006) compared with control subjects (subjects without airway hemorrhage). Those with hemorrhage had significantly higher preoperative right atrial pressure (P = .002) and pulmonary vascular resistance (P < .001) and a higher incidence of residual pulmonary hypertension (P = .005). Airway hemorrhage management included ECMO with bronchial blocker (n = 2), bronchial blocker without ECMO (n = 26), or withholding anticoagulation alone until bleeding subsided (n = 30). Mortality was significantly higher in those with airway hemorrhage compared with control subjects (13.8% vs 1.2%, P < .001). CONCLUSIONS: The incidence of postoperative airway hemorrhage is low but associated with significant mortality. Older age, female sex, preoperative hemoptysis, and worse preoperative pulmonary hypertension were associated with an increased risk of developing postoperative airway hemorrhage.

Taste and Smell Disturbances in Patients with Gastroparesis and Gastroesophageal Reflux Disease.

BACKGROUND/AIMS: Patients with gastroparesis and gastroesophageal reflux disease (GERD) often report decreased enjoyment when eating. Some patients remark that food does not smell or taste the same. To determine if taste and/or smell disturbances are present in patients with gastroparesis and/or GERD and relate these to gastrointestinal symptom severity. METHODS: Patients with gastroparesis and/or GERD completed questionnaires evaluating taste and smell (Taste and Smell Survey [TSS]), Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM), and Demographics. TSS questioned the nature of taste/smell changes and the impact on quality of life. PAGI-SYM was used to calculate Gastroparesis Cardinal Symptom Index (GCSI) and Heartburn and Regurgitation Score (HB/RG). RESULTS: Seventy-six subjects were enrolled: healthy controls (n = 13), gastroparesis alone (n = 30), GERD alone (n = 10), and both gastroparesis and GERD (n = 23). Taste and smell disturbances were higher in patients with gastroparesis, GERD, and both gastroparesis and GERD compared to healthy controls. Taste and smell abnormalities were significantly correlated (r = 0.530, P < 0.001). Taste score was strongly correlated with HB/RG (r = 0.637, P < 0.001) and with GCSI (r = 0.536, P < 0.001). Smell score was also strongly correlated to HB/RG (r = 0.513, P < 0.001) and GCSI (r = 0.495, P < 0.001). CONCLUSIONS: Taste and smell abnormalities are prominent in gastroparesis and GERD patients. Abnormalities in taste and smell are significantly correlated with both gastroparesis and GERD symptom severity. Awareness of this high prevalence of taste and smell dysfunction among patients with gastroparesis and GERD may help to better understand the food intolerances these patients often have.

Phase I clinical evaluation of seasonal influenza hemagglutinin (HA) DNA vaccine prime followed by trivalent influenza inactivated vaccine (IIV3) boost.

Annual influenza vaccination reduces the risks of influenza when the vaccines are well matched to circulating strains, but development of an approach that induces broader and more durable immune responses would be beneficial. We conducted two companion Phase 1 studies, VRC 307 and VRC 309, over sequential seasons (2008-2009 and 2009-2010) in which only the influenza B strain component of the vaccines differed. Objectives were safety and immunogenicity of prime-boost vaccination schedules. A schedule of DNA vaccine encoding for seasonal influenza hemagglutinins (HA) prime followed by seasonal trivalent influenza inactivated vaccine (IIV3) boost (HA DNA-IIV3) was compared to placebo (PBS)-IIV3 or IIV3-IIV3. Cumulatively, 111 adults were randomized to HA DNA-IIV3 (n=66), PBS-IIV3 (n=25) or IIV3-IIV3 (n=20). Safety was assessed by clinical observations, laboratory parameters and 7-day solicited reactogenicity. The seasonal HA DNA prime-IIV3 boost regimen was evaluated as safe and well tolerated. There were no serious adverse events. The local and systemic reactogenicity for HA DNA, IIV and placebo were reported predominantly as none or mild within the first 5days post-vaccination. There was no significant difference in immunogenicity detected between the treatment groups as evaluated by hemagglutination inhibition (HAI) assay. The studies demonstrated the safety and immunogenicity of seasonal HA DNA-IIV3 regimen, but the 3-4week prime-boost interval was suboptimal for improving influenza-specific immune responses. This is consistent with observations in avian H5 DNA vaccine prime-boost studies in which a long interval, but not a short interval, was associated with improved immunogenicity. TRIAL REGISTRATION: NCT00858611 for VRC 307 and NCT00995982 for VRC 309.