Adoption of a dedicated multidisciplinary team is associated with improved survival in acute pulmonary embolism.

BACKGROUND: Acute pulmonary embolism remains a significant cause of mortality and morbidity worldwide. Benefit of recently developed multidisciplinary PE response teams (PERT) with higher utilization of advanced therapies has not been established. METHODS: To evaluate patient-centered outcomes and cost-effectiveness of a multidisciplinary PERT we performed a retrospective analysis of 554 patients with acute PE at the university of Virginia between July 2014 and June 2015 (pre-PERT era) and between April 2017 through October 2018 (PERT era). Six-month survival, hospital length-of-stay (LOS), type of PE therapy, and in-hospital bleeding were assessed upon collected data. RESULTS: 317 consecutive patients were treated for acute PE during an 18-month period following institution of a multidisciplinary PE program; for 120 patients PERT was activated (PA), the remaining 197 patients with acute PE were considered as a separate, contemporary group (NPA). The historical, comparator cohort (PP) was composed of 237 patients. These 3 groups were similar in terms of baseline demographics, comorbidities and risk, as assessed by the Pulmonary Embolism Severity Index (PESI). Patients in the historical cohort demonstrated worsened survival when compared with patients treated during the PERT era. During the PERT era no statistically significant difference in survival was observed in the PA group when compared to the NPA group despite significantly higher severity of illness among PA patients. Hospital LOS was not different in the PA group when compared to either the NPA or PP group. Hospital costs did not differ among the 3 cohorts. 30-day re-admission rates were significantly lower during the PERT era. Rates of advanced therapies were significantly higher during the PERT era (9.1% vs. 2%) and were concentrated in the PA group (21.7% vs. 1.5%) without any significant rise in in-hospital bleeding complications. CONCLUSIONS: At our institution, all-cause mortality in patients with acute PE has significantly and durably decreased with the adoption of a PERT program without incurring additional hospital costs or protracting hospital LOS. Our data suggest that the adoption of a multidisciplinary approach at some institutions may provide benefit to select patients with acute PE.

Role of medical and molecular imaging in COPD.

Chronic obstructive pulmonary disease (COPD) is expected to climb on the podium of the leading causes of mortality worldwide in the upcoming decade. Clinical diagnosis of COPD has classically relied upon detecting irreversible airflow obstruction on pulmonary function testing as a global assessment of pulmonary physiology. However, the outcome is still not favorable to decrease mortality due to COPD. Progress made in both medical and molecular imaging fields are beginning to offer additional tools to address this clinical problem. This review aims to describe medical and molecular imaging modalities used to diagnose COPD and to select patients for appropriate treatments and to monitor response to therapy.

Treatment of Comorbid Obstructive Sleep Apnea by Upper Airway Stimulation Results in Resolution of Debilitating Symptoms of Restless Legs Syndrome.

ABSTRACT: An association between restless legs syndrome (RLS) and obstructive sleep apnea (OSA) has been suggested for decades but has been questioned in recent years given the apparently similar prevalence of RLS among patients with OSA and the general population. Still, marked improvement in symptoms of RLS has been reported in patients with OSA treated with continuous positive airway pressure (CPAP). Whether the effect of OSA treatment on RLS extends to modalities of OSA treatment other than CPAP remains an open question. Here, we report the case of a patient with OSA and comorbid debilitating RLS who underwent upper airway stimulation device implantation and subsequently experienced near-resolution of her severe RLS symptoms. Upper airway stimulation devices may be an option for patients with OSA and severe RLS intolerant to conventional CPAP modalities.

Vasopressin use in critically ill cirrhosis patients with catecholamine-resistant septic shock: The CVICU cohort.

AIM: To examine patient-centered outcomes with vasopressin (AVP) use in patients with cirrhosis with catecholamine-refractory septic shock. METHODS: We conducted a single center, retrospective cohort study enrolling adult patients with cirrhosis treated for catecholamine-resistant septic shock in the intensive care unit (ICU) from March 2011 through December 2013. Other etiologies of shock were excluded. Multivariable regression models were constructed for seven and 28-d mortality comparing AVP as a second-line therapy to a group of all other vasoactive agents. RESULTS: Forty-five consecutive patients with cirrhosis were treated for catecholamine-resistant septic shock; 21 received AVP while the remaining 24 received another agent [phenylephrine (10), dopamine (6), norepinephrine (4), dobutamine (2), milrinone (2)]. In general, no significant differences in baseline demographics, etiology of cirrhosis, laboratory values, vital signs or ICU mortality/severity of illness scores were observed with the exception of higher MELD scores in the AVP group (32.4, 95%CI: 28.6-36.2 vs 27.1, 95%CI: 23.6-30.6, P = 0.041). No statistically significant difference was observed in unadjusted 7-d (52.4% AVP vs 58.3% and P = 0.408) or 28-d mortality (81.0% AVP vs 87.5% non-AVP, P = 0.371). Corticosteroid administration was associated with lower 28-d mortality (HR = 0.37, 95%CI: 0.16-0.86, P = 0.021) independent of AVP use. CONCLUSION: AVP is similar in terms of patient centered outcomes of seven and 28-d mortality, in comparison to all other vasopressors when used as a second line vasoactive agent in catecholamine resistant septic shock. Large-scale prospective study would help to refine current consensus standards and provide further support to our findings.

Cancer vaccines. Any future?

The idea that vaccination can be used to fight cancer is not new. Approximately 100 years ago, researchers attempted to stimulate a tumor-specific, therapeutic immune response to tumors by injecting patients with cells and extracts from their own tumors, or tumors of the same type from different individuals. During the last decade, great efforts have been made to develop immunotherapeutic approaches for the treatment of malignant diseases as alternatives to traditional chemo- and radiotherapy. A quintessential goal of immunotherapy in cancer is treatment with vaccines that elicit potent anti-tumor immune responses without side effects. In this article, we have attempted to review some of the most problematic issues facing the development of cancer vaccines. With the prospect of immunosuppression, an ill-designed cancer vaccine can be more harmful than a no-benefit therapy. We have noted that "immunoediting" and "immunodominance" are the premier setbacks in peptide-based vaccines and therefore it appears necessary not only to manipulate the activity of a vast number of principal components but also to finely tune their concentrations in time and space. In the face of all these quandaries, it is at least doubtful that any reliable anti-cancer vaccine strategy will emerge in the near future.

Synthesis, characterization, and intracellular uptake of carboxyl-terminated poly(amidoamine) dendrimer-stabilized iron oxide nanoparticles.

We report the synthesis and characterization of a group of carboxyl-functionalized poly(amidoamine) (PAMAM) dendrimers of generation 3 (G3) that were used for the stabilization of superparamagnetic iron oxide (Fe(3)O(4)) nanoparticles (NPs). Folic acid (FA) molecules were conjugated onto the dendrimer surfaces in an attempt to achieve specific targeted imaging of tumor cells that overexpress FA receptors using dendrimer-stabilized Fe(3)O(4) NPs. Fe(3)O(4) NPs were synthesized using controlled co-precipitation of Fe(ii) and Fe(iii) ions and the formed dendrimer-stabilized Fe(3)O(4) NPs were characterized using transmission electron microscopy (TEM) and polyacrylamide gel electrophoresis (PAGE). The intracellular uptake of dendrimer-stabilized Fe(3)O(4) NPs was tested in vitro using KB cells (a human epithelial carcinoma cell line) that overexpress FA receptors. It appears that carboxyl-terminated PAMAM dendrimer-stabilized Fe(3)O(4) NPs can be uptaken by KB cells regardless of the repelling force between the negatively charged cells and the negatively charged particles. In the presence of a large amount of carboxyl terminal groups on the dendrimer surface, the receptor-mediated endocytosis of Fe(3)O(4) NPs stabilized by FA-modified dendrimers was not facilitated. It implies that the surface charge of dendrimer-stabilized magnetic iron oxide NPs in biological medium is an important factor influencing their biological performance.

HPLC analysis of functionalized poly(amidoamine) dendrimers and the interaction between a folate-dendrimer conjugate and folate binding protein.

Poly(amidoamine) (PAMAM) dendrimers of different generations with carboxyl, acetyl, and hydroxyl terminal groups and a folic acid (FA)-dendrimer conjugate were separated and analyzed using reverse-phase high performance liquid chromatography (HPLC). Analysis of both the individual PAMAM derivatives and the separation of mixed generations can be achieved using a linear gradient 0-50% acetonitrile (ACN) (balance water) within 40 min. We also show that PAMAMs with defined acetylation and carboxylation degrees can be analyzed using HPLC. Furthermore, a generation 5 dendrimer-FA conjugate (G5.75Ac-FA4; Ac denotes acetyl) was analyzed and its specific binding with a bovine folic acid binding protein (FBP) was monitored. The HPLC and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) results indicate the formation of three complexes after the binding of G5.75Ac-FA4 with FBP. Dendrimers with FA moieties show much higher specific binding capability with FBP than those without FA moieties. Findings from this study indicate that HPLC is an effective technique not only for characterization and separation of functionalized PAMAM dendrimers and conjugates but also for investigation of the interaction between dendrimers and biomolecules.