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Background: Covid-19 vaccination has started in the majority of the countries at the global level. Cancer patients are at high risk for infection, serious illness, and death from COVID-19 and need vaccination guidance and support. Guidance availability in the English language only is a major limit for recommendations’ delivery and their application in the world’s population and generates information inequalities across the different populations. Methods: Most of the available COVID-19 vaccination guidance for cancer patients was screened and scrutinized by the European Cancer Patients Coalition (ECPC) and an international oncology panel of 52 physicians from 33 countries. Results: A summary guidance was developed and provided in 28 languages in order to reach more than 70 percent of the global population. Conclusion: Language barrier and e-guidance availability in the native language are the most important barriers when communicating with patients. E-guidance availability in various native languages should be considered a major priority by international medical and health organizations that are communicating with patients at the global level.

Objective Chronic venous insufficiency (CVI) has an increased prevalence among obese individuals with body mass indices (BMI) over 30. A safe, efficacious, and evidence-based recommended treatment for CVI due to superficial venous reflux (SVR) in great saphenous veins (GSVs), small saphenous veins (SSVs), accessory saphenous veins (ASVs), and reflux in the perforator veins (PVs) is endovenous thermal ablation (EVTA). We sought to identify if BMI is an independent risk factor for recanalization after EVTA. Methods All patients with CVI were initially managed conservatively, and those with pathologic SVR refractory to compression therapy were offered EVTAs depending on the site of reflux. Sonographic confirmation of SVR was defined as >500 milliseconds of reflux in the GSVs, SSVs, and ASVs and a diameter >4 mm. PV reflux was confirmed as >350 milliseconds of reflux and a diameter >2.5 mm. All patients received a follow-up duplex ultrasound 1 week after the procedure, every 3 months for the first year, and every 6 months thereafter. Multivariate analysis with logistic regression was performed regarding patients' age, ablation modality (laser vs radiofrequency ablation), vein location and laterality, BMI, and recanalization. Results From 2013 to 2018, 9739 endovenous ablations were performed on 3070 patients. Endovenous laser was used in 3862 procedures and radiofrequency ablation in 5831 procedures. Veins treated with EVTA were distributed as follows: 6182 GSVs, 2509 SSVs, 597 ASVs, and 451 PVs. The mean patient age was 61.1 years (15-99, standard deviation [SD] ±15.6) with a mean BMI of 31.2 kg/m2 (13.7-69.5, SD ±7.3). A total of 68.4% patients were women and 31.4% men. The mean follow-up was 25.8 months (0-65.9, SD ±12.9). Multivariate statistical analysis with logistic regression was used to determine potential statistical significance between BMI and vein recanalization after EVTA. Overall, obese patients experienced more recanalizations than nonobese patients (P = .032), with an average BMI of 33 kg/m2 for recanalizations. PVs were statistically more likely to recanalize than any other vein (P = .0001). A secondary analysis was performed with the exclusion of PVs, due to their five times increased risk of recanalization, and showed no significant difference of recanalization across all BMI subgroups (P = .127). Conclusions BMI does not predict recanalization risk after EVTA, except for ablations performed on PVs.

International audience; Clinical manifestations of COVID-19 caused by the new coronavirus SARS-CoV-2 are associated with age1,2. Adults develop respiratory symptoms, which can progress to acute respiratory distress syndrome (ARDS) in the most severe form, while children are largely spared from respiratory illness but can develop a life-threatening multisystem inflammatory syndrome (MIS-C)3-5. Here, we show distinct antibody responses in children and adults after SARS-CoV-2 infection. Adult COVID-19 cohorts had anti-spike (S) IgG, IgM and IgA antibodies, as well as anti-nucleocapsid (N) IgG antibody, while children with and without MIS-C had reduced breadth of anti-SARS-CoV-2-specific antibodies, predominantly generating IgG antibodies specific for the S protein but not the N protein. Moreover, children with and without MIS-C had reduced neutralizing activity as compared to both adult COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children independent of whether they develop MIS-C, with implications for developing age-targeted strategies for testing and protecting the population.

Background: The number of fatalities due to coronavirus disease 2019 (COVID-19) is escalating with more than 800,000 deaths globally. The scientific community remains in urgent need of prognostic tools to determine the probability of survival in patients with COVID-19 and to determine the need for hospitalization. Methods: This is a retrospective cohort study of patients with a diagnosis of COVID-19 admitted to a tertiary center between March 2020 and July 2020. Patients age 18 years and older were stratified into two groups based on their troponin-I level in the first 24 h of admission (groups: elevated vs. normal). The aim of the study is to explore the utility of cardiac troponin-I level for early prognostication of patients with COVID-19. Results: This cohort of 257 patients included 122/257 (47%) women with a mean age of 63 ± 17 years. Patients with an elevated troponin-I level were more likely to be older (77 ± 13 vs. 58 ± 16 years, P < 0.0001), have a history of hypertension (P < 0.0001), diabetes mellitus (P = 0.0019), atrial fibrillation or flutter (P = 0.0009), coronary artery disease (P < 0.0001), and chronic heart failure (P = 0.0011). Patients with an elevated troponin-I level in the first 24 h of admission were more likely to have higher in-hospital mortality (52% vs. 10%, P < 0.0001). Troponin-I level in the first 24 h of admission had a negative predictive value of 89.7% and a positive predictive value of 51.9% for all-cause in-hospital mortality. Conclusions: Troponin-I elevation is commonly seen in patients with COVID-19 and is significantly associated with fatal outcomes. However, a normal troponin-I level in the first 24 h of admission had a high negative predictive value for all-cause in-hospital mortality, thereby predicting favorable survival at the time of discharge. Cardiol Res. 2020;11(6):398-404 doi: https://doi.org/10.14740/cr1159

BACKGROUND AND AIM Impella is frequently used to unload the left ventricle in patients with cardiogenic shock on venoarterial extracorporeal membrane oxygenation (VA-ECMO). There is limited data regarding the use of this strategy. This study aims to evaluate the safety and efficacy of the said strategy. METHODS A systematic search for studies comparing Impella plus VA-ECMO (ECVAD) vs VA-ECMO alone was performed using Pubmed, Cochrane Library, and Scopus. Studies meeting inclusion criteria were then used to perform a meta-analysis. RESULTS Three studies involving 448 patients were included in the final analysis. In total, 117 (26%) patients were female, mean age was 57 years. VA-ECMO was placed in 355 out of 448 (79%) patients, while ECVAD was placed in 93 out of 448 (21%). Death occurred in 49 out of 93 (52.6%) patients on ECVAD and 226 out of 355 (63.6%) on ECMO, relative risk (RR): 0.76, confidence interval (CI), 95% (0.62-0.94) P = .01. Hemolysis was present in 46 (49.4%) patients in the ECVAD vs 67 (18%) in the ECMO group, RR: 2.64, CI, 95% (1.97-3.55) P

A Think-Tank Meeting was convened by the National Cancer Institute (NCI) to solicit experts' opinion on the development and application of multiomic single-cell analyses, and especially single-cell proteomics, to improve the development of a new generation of biomarkers for cancer risk, early detection, diagnosis, and prognosis as well as to discuss the discovery of new targets for prevention and therapy. It is anticipated that such markers and targets will be based on cellular, subcellular, molecular, and functional aberrations within the lesion and within individual cells. Single-cell proteomic data will be essential for the establishment of new tools with searchable and scalable features that include spatial and temporal cartographies of premalignant and malignant lesions. Challenges and potential solutions that were discussed included (i) The best way/s to analyze single-cells from fresh and preserved tissue; (ii) Detection and analysis of secreted molecules and from single cells, especially from a tissue slice; (iii) Detection of new, previously undocumented cell type/s in the premalignant and early stage cancer tissue microenvironment; (iv) Multiomic integration of data to support and inform proteomic measurements; (v) Subcellular organelles-identifying abnormal structure, function, distribution, and location within individual premalignant and malignant cells; (vi) How to improve the dynamic range of single-cell proteomic measurements for discovery of differentially expressed proteins and their post-translational modifications (PTM); (vii) The depth of coverage measured concurrently using single-cell techniques; (viii) Quantitation - absolute or semiquantitative? (ix) Single methodology or multiplexed combinations? (x) Application of analytical methods for identification of biologically significant subsets; (xi) Data visualization of N-dimensional data sets; (xii) How to construct intercellular signaling networks in individual cells within premalignant tumor microenvironments (TME); (xiii) Associations between intrinsic cellular processes and extrinsic stimuli; (xiv) How to predict cellular responses to stress-inducing stimuli; (xv) Identification of new markers for prediction of progression from precursor, benign, and localized lesions to invasive cancer, based on spatial and temporal changes within individual cells; (xvi) Identification of new targets for immunoprevention or immunotherapy-identification of neoantigens and surfactome of individual cells within a lesion.

Objective Proximal venous outflow obstruction (PVOO) in the iliac veins and superficial venous disease are inter-related in ways not fully understood. We observed among our patients undergoing vein stent placement for PVOO a significant number having had prior endovenous thermal ablations (EVTA) in their history. This study was undertaken to better characterize these patients and develop an algorithm in their management. Methods In a combined retrospective and prospective data registry of 682 patients who underwent vein stent placement for chronic PVOO at a single institution from March 2013 to November 2017, 100 limbs of 99 patients (14.5% of all patients) had a history of EVTA or other superficial venous procedures before their vein stenting. Limbs with dilated truncal veins on ultrasound examination or limbs that underwent poststent EVTA or superficial venous procedures were excluded. The mean age of these 99 patients was 60.2 years (range, 28-88 years; standard deviation, 13.855). Fifty-one percent of the patients were male. The most common presenting symptom of the patient cohort was edema (n = 59), followed by venous-related skin changes (n = 22). Results Bilateral stents were performed in 58%, with a mean number of 2.06 stents per patient. EVTA was the primary superficial vein procedure in 97%. Bilateral EVTA were performed in 53% and unilateral EVTA in 47%. The mean time between the first EVTA to vein stenting was 1202.7 days. Patients were followed at 30 days, 90 days, 6 months, 1 year, and >1 year. The outcome for each patient at each postoperative visit was compared with preoperative parameters (subject's assessment, physical examination, and provider assessment) and was scored as follows: -1 (worse than preoperative), 0 (no change), +1 (mildly improved), +2 (significantly improved), or +3 (completely recovered). The mean outcome score at 30 days was 1.63 (84 patients), 2.05 at 90 days (62 patients), 2.09 at 6 months (74 patients), 1.93 at 1 year (54 patients), and 1.97 at >1 year (39 patients). Conclusions Approximately 15% of patients undergoing vein stent placement for chronic PVOO have an antecedent history of superficial venous disease and EVTA. PVOO should be considered and the patient evaluated accordingly if symptoms persisted or recurred after EVTA. Vein stent placement among these patients with PVOO will result in further symptomatic relief, but complete symptomatic relief is not observed in everyone. The algorithm for the management of these patients warrants further investigation.

Objective: Mice genetically deficient in endothelial nitric oxide synthase (Nos3 −/− ) have fasting hyperinsulinemia and hepatic insulin resistance, indicating the importance of Nos3 (nitric oxide synthase) in maintaining metabolic homeostasis. Although the current paradigm holds that these metabolic effects are derived specifically from the expression of Nos3 in the endothelium, it has been established that bone marrow–derived cells also express Nos3. The aim of this study was to investigate whether bone marrow–derived cell Nos3 is important in maintaining metabolic homeostasis. Approach and Results: To test the hypothesis that bone marrow–derived cell Nos3 contributes to metabolic homeostasis, we generated chimeric male mice deficient or competent for Nos3 expression in circulating blood cells. These mice were placed on a low-fat diet for 5 weeks, a time period which is known to induce hepatic insulin resistance in global Nos3-deficient mice but not in wild-type C57Bl/6 mice. Surprisingly, we found that the absence of Nos3 in the bone marrow–derived component is associated with hepatic insulin resistance and that restoration of Nos3 in the bone marrow–derived component in global Nos3-deficient mice is sufficient to restore hepatic insulin sensitivity. Furthermore, we found that overexpression of Nos3 in bone marrow–derived component in wild-type mice attenuates the development of hepatic insulin resistance during high-fat feeding. Finally, compared with wild-type macrophages, the loss of macrophage Nos3 is associated with increased inflammatory responses to lipopolysaccharides and reduced anti-inflammatory responses to IL-4, a macrophage phenotype associated with the development of hepatic and systemic insulin resistance. Conclusions: These results would suggest that the metabolic and hepatic consequences of high-fat feeding are mediated by loss of Nos3/nitric oxide actions in bone marrow–derived cells, not in endothelial cells.

Background Endovenous thermal ablation has become the procedure of choice in the treatment of superficial venous reflux disease. The current armamentarium of devices and techniques aimed at the elimination of saphenous reflux offers surgeons and interventionalists a variety of treatment options; however, there is a lack of data comparing the safety of these products. The most concerning complication after endovenous thermal ablation is endothermal heat-induced thrombosis (EHIT) due to the risk of progression to deep venous thrombosis. This study aimed to compare the incidence rate of EHIT between radiofrequency ablation (RFA) and endovenous laser therapy (EVLT). Methods This was a single-center, office-based, retrospective study over the course of 5 years, in which 3,218 consecutive patients underwent 10,029 endovenous saphenous ablations. The patient cohort was 66.2% female, with an average age of 61.9 years. At the time of each individual intervention, 24, 212, 3,620, 4,806, 200, and 1,167 patients had Clinical-Etiology-Anatomy-Pathophysiology disease 1, 2, 3, 4, 5, and 6, respectively. Results There was a total of 3,983 EVLT and 6,091 RFA procedures. The most common vessel treated was the great saphenous vein, 63.6% of the time, followed by the small saphenous vein (25.6%), accessory saphenous vein (6.1%), and perforator vein (4.6%). There were 186 cases of EHIT, with 137 (73.6%) identified as type 1 as per the Kabnick classification. Endovenous ablation performed via RFA resulted in significantly more cases of EHIT than of EVLT (109 vs. 77; P = 0.034; odds ratio = 1.52), which was confirmed by a multivariate analysis. Conclusions In the largest single-center study of endovenous saphenous ablations to date, RFA was shown to pose a significantly higher risk of EHIT than of EVLT.

INTRODUCTION: Acute pancreatitis (AP) and acute aortic dissection (AAD) are medical emergencies that must be promptly recognized to avoid the development of life-threatening complications. Both of these diseases can present with chest or epigastric pain which can radiate to the back, thus, early suspicion based on clinical presentation and risk factors is essential. We present the case of a 56-year-old patient initially diagnosed with AP who was later found to have an AAD. CLINICAL FINDINGS: A 56-year-old man with a history of alcohol abuse presented with 1 day of diffuse abdominal pain, nausea and vomiting. His lipase was 3,909 U/L and creatinine was 2.19 mg/dL and he was diagnosed with acute alcoholic pancreatitis with acute kidney injury. A non-contrast computed tomography (NCCT) scan of the abdomen showed aortic calcifications. He received 3.8 liters of fluids after which he developed acute respiratory distress requiring intubation. A workup for extracorporeal membrane oxygenation (ECMO) was initiated, given the suspicion of acute respiratory distress syndrome (ARDS) due to pancreatitis. This revealed an AAD with severe aortic regurgitation on transthoracic echocardiography (TTE). CT angiogram showed type A AAD involving the aortic root, ascending aorta, descending aorta, suprarenal and infrarenal abdominal aorta. The celiac axis, superior mesenteric artery (SMA) and inferior mesenteric artery (IMA) were patent. OUTCOMES: The patient underwent type A AAD repair with mechanical aortic valve replacement and survived the acute event. His AP resolved and he was discharged home with appropriate follow up. CONCLUSION: We hypothesize that if our patient was not assessed for ECMO, the finding of AAD would have been a diagnostic challenge. AP secondary to AAD is rare but a high index of suspicion is required for diagnosis.

INTRODUCTION AND OBJECTIVE:We present cumulative results describing the clinical performance of IsoPSA, a blood-based, structure-focused assay for high grade prostate cancer, in a large scale, pros...

A significant percentage of patients with gastroesophageal reflux disease (GERD) will not respond to proton pump inhibitor (PPI) therapy. The causes of PPI-refractory GERD are numerous and diverse, and include adherence, persistent acid, functional disorders, nonacid reflux, and PPI bioavailability. The evaluation should start with a symptom assessment and may progress to imaging, endoscopy, and monitoring of esophageal pH, impedance, and bilirubin. There are a variety of pharmacologic and procedural interventions that should be selected based on the underlying mechanism of PPI failure. Pharmacologic treatments can include antacids, prokinetics, alginates, bile acid binders, reflux inhibitors, and antidepressants. Procedural options include laparoscopic fundoplication and LINX as well as endoscopic procedures, such as transoral incisionless fundoplication and Stretta. Several alternative and complementary treatments of possible benefit also exist.

With wider recognition of left renal vein compression / obstruction, especially as an incidental finding, the significance as it relates to the patient's symptoms needs to be evaluated in light of variable practices and results of treatment. This communication deals with problems of diagnosis, clinical significance, options and indications for treatment.

Early during the Coronavirus disease 2019 (Covid-19) pandemic, concerns were raised regarding potential adverse outcomes in patients taking angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs). These concerns were based on animal studies showing increased ACE-2 expression in mice treated with ACEI/ARB. This is a single-center, retrospective, cohort study of 289 patients diagnosed with 2019 Novel Coronavirus (SARS-CoV-2) hospitalized between March of 2020 and June of 2020. The study was intended to investigate the impact of ACEIs and/or ARBs on in-hospital mortality, intensive care unit (ICU) admission, postadmission hemodialysis requirement, and the need for mechanical ventilation in patients with COVID-19. This cohort of 289 patients included 139 of 289 women (48%) with a mean age of 61 ± 19 years. Patients using ACEIs/ARBs were older (69.68 vs. 57.9 years; P0.0001), more likely to have a history of hypertension (97% vs. 36%; P0.0001), diabetes mellitus (48% vs. 20.9%; P0.0001), chronic heart failure (11.39% vs. 4.29%; P0.0512), coronary artery disease (20.25% vs. 7.14%; P0.0025), stroke/Transient Ischemic Attack (7.59% vs. 2.38%; P0.0761), chronic kidney disease (11.39% vs. 3.33%; P0.0167), atrial fibrillation/flutter (18.99% vs. 7.14%; P0.0080), and dementia (22.7% vs. 11.4%; P0.0233) compared with the nonuser group. There was significantly higher in-hospital mortality in patients using ACEIs/ARBs than nonusers, respectively (32.9% vs. 15.2%; P0.0015). However, a multivariate logistics regression analysis performed to adjust for common confounders demonstrated no significant difference in all-cause in-patient mortality (P 0.7141). Admission to ICU, postadmission hemodialysis requirement, and mechanical ventilation showed no significant differences between the 2 groups (P = NS). This study suggests that the use of ACEIs and ARBs in patients with COVID-19 was not found to significantly increase all-cause in-hospital mortality, ICU admissions, and hemodialysis and mechanical ventilation requirements.

Objective Iliac vein stenting of nonthrombotic iliac vein lesions is an evolving treatment course for management of chronic venous insufficiency. To characterize these lesions, we examined our experience treating these lesions with balloon venoplasty before stenting. Methods A retrospective analysis was performed to study all patients who underwent venograms with venoplasty and stenting of iliac veins from February 2013 to July 2016. All patients included in the study were treated with a trial conservative management for 3 consecutive months before venogram and, if indicated, venoplasty was performed. If a greater than 50% reduction in cross-sectional area or diameter was observed on intravascular ultrasound examination, the stenotic area was treated with balloon angioplasty, sized to nonstenotic distal vein segment (range, 10 × 40 mm to 16 × 60 mm). Intravascular ultrasound examination was also used to measure the area of stenotic iliofemoral veins before and after balloon angioplasty. Results A total of 1021 venograms with venoplasty and stenting of iliac veins were performed in 713 patients from February 2013 to July 2016. The mean age of the study population age was 64.88 years (range, 21-99 years; standard deviation [SD], 14.57), with 451 female and 262 male patients. Before angioplasty, the mean cross-sectional stenotic area was 67.97 mm2 (range, 6-318 mm2; SD, 34.87). After balloon angioplasty, the mean stenotic area increased to 78.80 (range, 6-334 mm2; SD, 44.50; P 10% of baseline before venoplasty); group B, decreased ( Conclusions Our data show there is a highly variable response after venoplasty of stenotic area of nonthrombotic iliac vein lesions. Balloon venoplasty showed greater improvement in improving the area of stenotic left-sided lesions. However, stenting of the lesions should be performed routinely owing to recoil and spasm in lesions.

Objective Iliac vein stent placement is an increasingly common procedure in the treatment of chronic proximal venous outflow obstruction (PVOO), but secondary interventions after vein stent placement remain poorly characterized. Our goal was to identify the incidence, indications, operative findings, and outcomes of secondary interventions after the primary iliac vein stent procedure at a single institution. Methods We retrospectively reviewed the clinical history of 490 patients (57.6% female, 42.4% male; mean age, 60.77 years [range, 18-92 years]; 93.28% follow-up, with a mean follow-up of 308.59 days) who underwent iliac vein stent placement for PVOO between October 2013 and January 2016. We evaluated the clinical presentation, intraoperative findings, and outcomes of those patients requiring a secondary intervention after an initial iliac vein stent procedure. Results Secondary interventions after an initial stent placement were identified in 50 of 490 patients (10.2%; mean age, 61.54 years [range, 19-92 years]; 58% female [n = 29]). At the time of each individual intervention, 1, 18, 17, 1, and 13 patients had Clinical, Etiology, Anatomy, and Pathophysiology class 2, 3, 4, 5, and 6 disease, respectively. Of these 50 patients, 58% (n = 29) of secondary interventions were due to recurrence of symptoms after the initial stent surgery, 18% (n = 9) were due to the development of new symptoms, and 24% (n = 12) were due to persistence of symptoms. The primary cause of PVOO in the patient cohort was 52% (n = 26) extrinsic iliac vein compression, 28% post-thrombotic, and 20% mixed. Intraoperative findings during the secondary intervention included malposition or angulation of the stent (6% [n = 3]); acute deep venous thrombosis/thrombosis (14% [n = 7]); an additional lesion, that is, stenosis in a native iliac vein proximal or distal to the original lesion (68% [n = 34]); stenosis within the stent, that is, stent stenosis without finding of thrombus or isolated, focal intrastent thrombosis (38% [n = 19]); and impairment of flow of the contralateral vessel from the previously placed stent (6% [n = 3]). The types of secondary interventions included placement of a new stent (86% [n = 43]), isolated balloon angioplasty alone (10% [n = 5]), and catheter pharmacomechanical thrombectomy (14% [n = 7]). Symptomatic improvement was observed after the secondary intervention in 90% of patients (n = 45), whereas only 2% (n = 1) of patients experienced only a transient improvement, and 8% of patients (n = 4) reported no improvement in their symptoms after the secondary interventions. Conclusions This study establishes a secondary intervention rate of 10.2% after iliac vein stent placement for chronic PVOO and identifies discrete and definable intraoperative findings as targets for quality improvement. The very good results strongly suggest that an aggressive approach to treatment of these complications is warranted.

Background Distress is common among cancer patients and leads to worse postoperative outcomes. Surgeons are often the first physicians to have in-depth conversations with patients about a new colorectal cancer diagnosis; therefore, it is important that these surgeons understand how patients cope with the distress of a diagnosis and how they can help patients manage this distress. Methods Patients with colorectal cancer were recruited from an outpatient surgery clinic. Purposive sampling was used to recruit patients if they were either planning to undergo surgery or had undergone surgery within six months. In-depth, open-ended, individual qualitative interviews were performed. Grounded theory was used to develop themes regarding patients’ coping strategies and beliefs regarding the role of the surgeon in helping them cope. Results Patients described their own internal coping strategies using problem-focused, emotion-focused, and meaning-focused techniques. Patients also reported the importance of their social support network for coping. Patients believed surgeons and their teams should help patients manage the emotional components of their cancer diagnosis and surgical experience, especially if patients were experiencing high levels of distress or had inadequate coping skills. They did not believe surgeons themselves should be primarily responsible for helping them cope. Conclusion In order for surgeons to guide diagnosis and initial management of distress in colorectal cancer patients undergoing surgery, they should screen patients for distress, identify and strengthen patients’ own coping strategies, facilitate a strong social support network, and provide patients with the option to obtain further support from the surgeon's office.

Acute type B aortic dissection with origin of the left subclavian artery (LSA) is generally managed with endovascular therapy for acute coverage of the LSA with: 1) no revascularization; 2) revascularization with open methods; or 3) endovascular revascularization. To identify an alternative solution, we critically evaluated a small cohort of patients who had partial coverage of their LSA.Three thoracic endovascular repairs were performed from January-March 2015. Patients were deemed eligible for endovascular repair after they had failed conservative management. Indications included acute type B dissection with lower extremity ischemia, ruptured dissection, and persistent symptoms of dissection after medical therapy.Technical success was achieved in all three patients, and all procedures were performed percutaneously. The mean distance between the ostium of the LSA and the entry point of dissection was 11.1±3.4 mm. Within the 30-day postoperative period, there were no deaths, aortic ruptures, myocardial infarctions, or conversions to open repair. Freedom from re-intervention was noted in all 3 patients. There was no spinal cord ischemia.There is no strong evidence to support the current optimal approach for treatment of the thoracic aorta. Partial coverage of LSA in patients with2 cm seal zones may be considered as an alternative. However, due to our small sample size, limited follow-up, and lack of comparison cohort, further investigation is necessary.

Objective: Expression of the extrahepatic acute-phase protein Saa3 (serum amyloid A3) increases in response to acute and chronic inflammatory stimuli and is elevated in adipose tissue and macrophages in obese mice. A recent report suggested that Saa3 is proatherogenic in male ApoE −/− mice. Because of our previous observation that female but not male Saa3-deficient mice are protected from obesity, adipose inflammation, and hyperlipidemia, we sought to determine whether Saa3 differentially modulates atherosclerosis in mice of both sexes. Approach and Results: To promote atherosclerosis, Saa3 +/+ and Saa3 −/− male and female mice were crossed with Ldlr −/− mice. All mice consumed a diet high in saturated fat and sucrose with 0.15% added cholesterol for 16 weeks. Plasma lipids and atherosclerosis levels were assessed. Female Saa3 −/− Ldlr −/− mice exhibited elevated cholesterol levels relative to Saa3 +/+ Ldlr −/− controls and exhibited increased atherosclerosis, while male Saa3 −/− Ldlr −/− mice were protected from atherosclerosis. Data from the hybrid mouse diversity panel revealed that Saa3 associates strongly with inflammatory, Trem2-associated, and tissue remodeling genes and pathways in males but not females, an effect confirmed in liver tissue, atherosclerotic lesions, and cultured macrophages. Macrophages isolated from male and female mice showed differential inflammatory effects of Saa3 deficiency, an effect linked with sex steroid signaling. Cholesterol efflux capacity was increased in Saa3 −/− males only. Conclusions: Saa3 is proatherogenic in male but atheroprotective in female mice, effects that may be related to sex-specific relationships between Saa3, cholesterol metabolism, inflammatory genes, and Trem2 macrophages.

Immune response dynamics in COVID-19 and its severe manifestations have largely been studied in circulation. Here, we examined the relationship between immune processes in the respiratory tract and circulation through longitudinal phenotypic, transcriptomic and cytokine profiling of paired airway and blood samples from patients with severe COVID-19 relative to heathy controls. In COVID-19 airways, T cells exhibited activated, tissue-resident, and protective profiles; higher T cell frequencies correlated with survival and younger age. Myeloid cells in COVID-19 airways featured hyper-inflammatory signatures and higher frequencies of these cells correlated with mortality and older age. In COVID-19 blood, aberrant CD163+ monocytes predominated over conventional monocytes, and were found in corresponding airway samples and in damaged alveoli. High levels of myeloid chemoattractants in airways suggest recruitment of these cells through a CCL2-CCR2 chemokine axis. Our findings provide insights into immune processes driving COVID-19 lung pathology with therapeutic implications for targeting inflammation in the respiratory tract., Through longitudinal profiling of paired airway and blood from patients with severe COVID-19, Szabo et al. reveal airway immune responses that correlate with age and outcome. They further identify coordinate roles for T and myeloid cells in the respiratory tract and circulation in perpetuating lung pathology and disease pathogenesis.

Treatment of kidney stones is based on symptomatic medications which are associated with side effects such as gastrointestinal symptoms (e.g., nausea, vomiting) and hepatotoxicity. The search for effective plant extracts without the above side effects has demonstrated the involvement of antioxidants in the treatment of kidney stones. A local survey in Morocco has previously revealed the frequent use of Rubia tinctorum L. (RT) for the treatment of kidney stones. In this study, we first explored whether RT ethanolic (E-RT) and ethyl acetate (EA-RT) extracts of Rubia tinctorum L. could prevent the occurrence of urolithiasis in an experimental 0.75% ethylene glycol (EG) and 2% ammonium chloride (AC)-induced rat model. Secondly, we determined the potential antioxidant potency as well as the polyphenol composition of these extracts. An EG/AC regimen for 10 days induced the formation of bipyramid-shaped calcium oxalate crystals in the urine. Concomitantly, serum and urinary creatinine, urea, uric acid, phosphorus, calcium, sodium, potassium, and chloride were altered. The co-administration of both RT extracts prevented alterations in all these parameters. In the EG/AC-induced rat model, the antioxidants- and polyphenols-rich E-RT and EA-RT extracts significantly reduced the presence of calcium oxalate in the urine, and prevented serum and urinary biochemical alterations together with kidney tissue damage associated with urolithiasis. Moreover, we demonstrated that the beneficial preventive effects of E-RT co-administration were more pronounced than those obtained with EA-RT. The superiority of E-RT was associated with its more potent antioxidant effect, due to its high content in polyphenols.

INTRODUCTION: Estimated dry weight is used to guide fluid removal during outpatient hemodialysis sessions. Errors in estimated dry weight can result in intradialytic hypotension and interdialytic fluid overload. The goal of this study was to assess the accuracy of estimated dry weight by comparing it to the two-week post-transplant weight in two cohorts of hemodialysis patients. METHODS: This observational, multi-center, retrospective cohort study included maintenance hemodialysis patients who underwent kidney transplantation at two medical centers in Massachusetts. The relationship between estimated dry weight pre-transplant and weight at week 2 post-transplant in patients with good allograft function (serum creatinine ≤ 1.5 mg/dL) was analyzed. Estimated dry weight was considered accurate if it was within ±2% of the week 2 post-transplant weight. RESULTS: Fifty seven patients with good allograft function were identified: mean age 54±14 years, 32 (58%) from deceased donors, 22 (38.6%) females. 38 were Caucasian (66.7%), 11 Hispanic (19.3%), 3 black (5.3%), and 5 others (8.8%). 2-week mean post transplantation serum creatinine was 1.2±0.2 mg/dL. Mean (SD) estimated dry weight was 71.4±15.9. Before transplantation, only 14 (24.6%) patients were within ±2% of the 2-week post-transplant weight; 23 (40.3%) were above and 20 (35.1%) were below. CONCLUSIONS: Our point of view, based on the assumption that the weight of patients with good allograft function at 2 weeks post-transplant approaches their accurate dry weight, is that a majority of maintenance hemodialysis patients (75.4%) are hypervolemic or hypovolemic prior to renal transplantation. This highlights the importance of finding novel tools to achieve euvolemia in patients undertaking dialysis. Timely feedback regarding achieved weight 2 weeks post-transplant to treating nephrologists and dialysis centers may be a starting point for assessing accuracy of dry weight.

Malaria parasites use the RhopH complex for erythrocyte invasion and channel-mediated nutrient uptake. As the member proteins are unique to Plasmodium spp., how they interact and traffic through subcellular sites to serve these essential functions is unknown. We show that RhopH is synthesized as a soluble complex of CLAG3, RhopH2, and RhopH3 with 1:1:1 stoichiometry. After transfer to a new host cell, the complex crosses a vacuolar membrane surrounding the intracellular parasite and becomes integral to the erythrocyte membrane through a PTEX translocon-dependent process. We present a 2.9 Å single-particle cryo-electron microscopy structure of the trafficking complex, revealing that CLAG3 interacts with the other subunits over large surface areas. This soluble complex is tightly assembled with extensive disulfide bonding and predicted transmembrane helices shielded. We propose a large protein complex stabilized for trafficking but poised for host membrane insertion through large-scale rearrangements, paralleling smaller two-state pore-forming proteins in other organisms., eLife digest Malaria is an infectious disease caused by the family of Plasmodium parasites, which pass between mosquitoes and animals to complete their life cycle. With one bite, mosquitoes can deposit up to one hundred malaria parasites into the human skin, from where they enter the bloodstream. After increasing their numbers in liver cells, the parasites hijack, invade and remodel red blood cells to create a safe space to grow and mature. This includes inserting holes in the membrane of red blood cells to take up nutrients from the bloodstream. A complex of three tightly bound RhopH proteins plays an important role in these processes. These proteins are unique to malaria parasites, and so far, it has been unclear how they collaborate to perform these specialist roles. Here, Schureck et al. have purified the RhopH complex from Plasmodium-infected human blood to determine its structure and reveal how it moves within an infected red blood cell. Using cryo-electron microscopy to visualise the assembly in fine detail, Schureck et al. showed that the three proteins bind tightly to each other over large areas using multiple anchor points. As the three proteins are produced, they assemble into a complex that remains dissolved and free of parasite membranes until the proteins have been delivered to their target red blood cells. Some hours after delivery, specific sections of the RhopH complex are inserted into the red blood cell membrane to produce pores that allow them to take up nutrients and to grow. The study of Schureck et al. provides important new insights into how the RhopH complex serves multiple roles during Plasmodium infection of human red blood cells. The findings provide a framework for the development of effective antimalarial treatments that target RhopH proteins to block red blood cell invasion and nutrient uptake.

Purpose To review and indirectly compare the outcomes of minimally invasive therapies for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. Materials and Methods A literature search via Medline and Cochrane Central databases was completed for randomized control studies published between January 2000 to April 2020 for the following therapies: Rezum, Urolift, Aquablation, and prostate artery embolization (PAE). Data on the following variables were included: international Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax), quality of life (QoL), and post-void residual (PVR). Standard mean differences between treatments were compared through a meta-analysis using transurethral resection of the prostate (TURP) to assess differences in treatment effect. Results No significant difference in outcomes between therapies were noted for IPSS at the 3-, 6-, and 12-month follow-ups. Although outcomes for rezum were only available out to 3 months, there were no consistently significant differences in outcomes when comparing Aquablation vs PAE vs Rezum. TURP PVR was significantly better than Urolift at 3-, 6-, and 12 months. No significant differences in minor or major AEs were noted. Conclusion Although significant differences in outcomes were limited, aquablation and PAE were the most durable at 12 months. PAE has been well studied on multiple randomized control trials with minimal adverse events while aquablation has limited high quality data and has been associated with bleeding-related complications.

Introduction: The use of aggressive fluid therapy in patients with heart failure and reduced ejection fraction (HFrEF) who develop septic shock is controversial. Methods: This is a retrospective cohort study of 334 patients with heart failure (HF) and septic shock admitted to a tertiary cardiovascular center between 01/2015 and 06/2018. For this study, ejection fraction (EF) was dichotomized into Results: A total of 133(40%) patients had HFrEF, and 201(60%) patients had HFpEF (see Table 1, baseline characteristics). Early goal direct fluid therapy and vasopressors were equally implemented in all patients with HF that developed septic shock. Outcomes: There was no difference in in-hospital mortality for patients with HFrEF that developed septic shock when compared to patients with HFpEF, 64(48%) vs 102(51%) p=0.6542. Patients with HFrEF had a higher incidence of cardiogenic shock 25(19%) vs 9(4.5%) p Conclusions: Once patients with HF develop septic shock, the mortality is similar for both HFrEF and HFpEF. However, complications such as cardiogenic shock and 30-day readmission are more common in patients with HFrEF. A more individualized treatment approach is needed for this population.

ObjectiveEpidemiological studies suggest that the incidence of anorexia nervosa (AN) is increasing in younger populations, with some evidence that clinical differences occur according to age of onset (AOO), which may impact prognostic outcomes. The current study sought to compare eating disorder (ED) symptomatology, psychological distress and psychosocial function between early onset (EO), typical onset (TO) and later onset (LO) AN in a large sample of treatment-seeking patients with a diagnosis of AN.MethodsParticipants included 249 individuals with a diagnosis of AN who were assessed at an outpatient ED service. The sample was divided into three groups based on AOO; those with an AOO ≤14 years (N = 58) were termed ‘EO-AN’, those with an AOO between 15 and 18 years (N = 113) were termed ‘TO-AN’ and those with an AOO of > 18 years (N = 78) were termed ‘LO-AN’. Comparisons were made between AOO groups on assessments of ED symptomatology, psychological distress and psychosocial function.ResultsEO-AN patients reported a significantly longer illness duration than both TO-AN and LO-AN groups. After controlling for effect of illness duration, the EO-AN group demonstrated significantly higher ED symptomatology and dysmorphic concern compared to the LO-AN group. The EO-AN group demonstrated significantly decreased cognitive flexibility compared to both the TO-AN and LO-AN groups.DiscussionThese findings suggest that clinical differences do occur according to AOO in AN whereby EO-AN may represent a more severe form of illness that is not attributable to increased illness duration. Treatment strategies which specifically address patients with EO-AN may improve long term health outcomes and recovery.

Objective Iliac vein stenting is increasingly being explored for the treatment of chronic venous insufficiency. While venography is considered the gold standard for assessing iliac veins, some have proposed that intravascular ultrasound should be utilized instead due to its greater sensitivity at detecting stenotic lesions. Routinely, our service uses both intravascular ultrasound and venography, but we have noted that some patients cannot tolerate dye due to allergy, renal insufficiency, or deemed high-risk by the interventionalist due to uncontrolled medical co-morbidities. This study aimed to investigate whether forgoing dye had an impact on iliac vein stent thrombosis. Methods From 2012 to 2016, 1482 iliac vein procedures (91 intravascular ultrasound-only and 1391 intravascular ultrasound plus venography) were performed on 992 patients who failed conservative treatment for chronic venous insufficiency. Our mean patient age was 65.8 years (range 21–99; SD ± 14.3) with 347 male and 645 female patients. The clinical presenting symptoms per clinical–etiology–anatomy–pathophysiology classification for the intravascular ultrasound-only cohort were C1:0, C2:3, C3:31, C433, C5:5, C6:20 and for the intravascular ultrasound plus venography cohort were C1:0, C2:24, C3:566, C4:583, C5:30, C6:188. Stent thrombi that developed within or at 30 days of stenting were categorized as early and greater than 30 days as late. Transcutaneous duplex ultrasound classified stent thrombi as either partial or occlusive. Our average follow-up time was 19.4 months (0–42, SD ± 12.5). Results A total of 2.2% intravascular ultrasound-only patients versus 2.75% intravascular ultrasound plus venogram patients developed early stent thrombosis, p = 0.35. Early partial stent thrombosis occurred in 1.1% of the intravascular ultrasound-only group versus 2.6% of the intravascular ultrasound plus venogram group, p = 0.38. Early occlusive stent thromboses occurred in 1.1% of intravascular ultrasound-only patients and 0.15% of intravascular ultrasound plus venogram patients, p = 0.06. Late stent thromboses developed in 4% of patients in the intravascular ultrasound-only cohort and 4% in the intravascular ultrasound plus venogram cohort, p = 0.97. Late partial stent thromboses occurred in 2.7% of intravascular ultrasound-only patients versus 2.6% in intravascular ultrasound plus venogram patients, p = 0.99. Late occlusive stent thromboses occurred in 1.3% of intravascular ultrasound-only patients versus 1.4% of intravascular ultrasound plus venogram patients, p = 0.95. Moreover, the formation of any stent was 6.2% in the intravascular ultrasound-only versus 6.75% in the intravascular ultrasound plus venogram group, p = 0.55. Conclusion Results of our study show no significant difference in stent thrombosis between the intravascular ultrasound-only and intravascular ultrasound plus venogram cohorts. This concludes that using intravascular ultrasound alone is safe for iliac vein stenting.

Background Data on urgent transcatheter aortic valve replacement (TAVR) as rescue therapy for acute decompensated heart failure (ADHF) due to severe aortic stenosis (AS) are limited. We sought to investigate the outcomes of patients who underwent urgent transcatheter aortic valve replacement (TAVR) in a single institution. Methods This is a retrospective cohort study of 602 patients with a history of heart failure (HF) due to AS who underwent TAVR between April 2012 and July 2017. We stratified patient cohort into urgent (n=139) and elective (n=463) TAVR. Urgent TAVR was defined as patients who were admitted for ADHF and underwent TAVR during the same hospitalization. Patients that underwent urgent TAVR for other reasons were excluded. Results Rates of postoperative intra-aortic balloon pump requirement, atrial fibrillation, dialysis requirement, vascular complications, and stroke were similar between the two groups. Compared with elective TAVR, patients undergoing urgent TAVR had a higher rate of cardiac arrest (5.7% vs 1.3%, p=0.005), longer length of stay (LOS) (11 vs. 5, p

Objective This guideline will provide the practicing endocrinologist with an approach to the assessment and treatment of dyslipidemia in patients with endocrine diseases, with the objective of preventing cardiovascular (CV) events and triglyceride-induced pancreatitis. The guideline reviews data on dyslipidemia and atherosclerotic cardiovascular disease (ASCVD) risk in patients with endocrine disorders and discusses the evidence for the correction of dyslipidemia by treatment of the endocrine disease. The guideline also addresses whether treatment of the endocrine disease reduces ASCVD risk. Conclusion This guideline focuses on lipid and lipoprotein abnormalities associated with endocrine diseases, including diabetes mellitus, and whether treatment of the endocrine disorder improves not only the lipid abnormalities, but also CV outcomes. Based on the available evidence, recommendations are made for the assessment and management of dyslipidemia in patients with endocrine diseases.

Clinical manifestations of COVID-19 caused by the novel coronavirus SARS-CoV-2 are associated with age. While children are largely spared from severe respiratory disease, they can present with a SARS-CoV-2-associated multisystem inflammatory syndrome (MIS-C) similar to Kawasaki’s disease. Here, we show distinct antibody (Ab) responses in children with MIS-C compared to adults with severe COVID-19 causing acute respiratory distress syndrome (ARDS), and those who recovered from mild disease. There was a reduced breadth and specificity of anti-SARS-CoV-2-specific antibodies in MIS-C patients compared to the COVID patient groups; MIS-C predominantly generated IgG Abs specific for the Spike (S) protein but not for the nucleocapsid (N) protein, while the COVID-19 cohorts had anti-S IgG, IgM and IgA Abs, as well as anti-N IgG Abs. Moreover, MIS-C patients had reduced neutralizing activity compared to both COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children and adults who develop severe disease, with implications for optimizing treatments based on symptom and age.

Background Limited data exist about the impact of gender-specific outcomes in patients with heart failure (HF) who develop concomitant sepsis. Methods This is a retrospective cohort study of patients with HF who developed sepsis. Clinical outcomes, including in-hospital mortality, development of cardiogenic shock (CS), pulmonary edema requiring urgent intravenous diuretics (IVD), acute kidney injury (AKI), length of stay (LOS), and 30-day HF-related readmission, were evaluated in men vs. women. Results This cohort of 618 patients includes 272 (44%) women with a mean age of 75±14 years. Coronary artery disease (p

Description Ventricular septal rupture (VSR) is a rare complication after acute myocardial infarction (MI). The case presents an apical four chamber echocardiogram showing mid-septal discontinuity with lateral to medial movement of the transected ventricular septum during systole and diastole. Color Doppler demonstrates flow across the septum with extensive anatomic destruction of the ventricular septum.

Adipose tissue plays essential roles in maintaining lipid and glucose homeostasis. To date several types of adipose tissue have been identified, namely white, brown, and beige, that reside in various specific anatomical locations throughout the body. The cellular composition, secretome, and location of these adipose depots define their function in health and metabolic disease. In obesity, adipose tissue becomes dysfunctional, promoting a pro-inflammatory, hyperlipidemic and insulin resistant environment that contributes to type 2 diabetes mellitus (T2DM). Concurrently, similar features that result from adipose tissue dysfunction also promote cardiovascular disease (CVD) by mechanisms that can be augmented by T2DM. The mechanisms by which dysfunctional adipose tissue simultaneously promote T2DM and CVD, focusing on adipose tissue depot-specific adipokines, inflammatory profiles, and metabolism, will be the focus of this review. The impact that various T2DM and CVD treatment strategies have on adipose tissue function and body weight also will be discussed.

The Trigonella foenum-graecum L. seeds, in a dormant or sprouted state, have been largely investigated for their therapeutic activities such as being antidiabetic, antioxidant, cholesterol-lowering, and as a digestive enhancer too. Nevertheless, there are no studies evaluating the potential developmental toxicity of germinated grains despite the availability of numerous research studies demonstrating the teratogenicity effect of unsprouted seeds. Therefore, this research work was conducted to assess the impact of fenugreek sprouts on maternal and neurobehavioral developmental toxicities on mice. The lyophilized aqueous extract of germinated seeds was administered via oral gavage on a daily basis to five groups of mated female mice throughout pregnancy at doses of 200, 500, 800, and 1000 mg/kg/day and the control group was administered distilled water. Maternal reproductive toxicity was evaluated, and the surviving pups were assessed for their physical development, malformation, and neurobehavioral toxicity by using a battery of tests from birth to the 25th postnatal day. Additionally, the aqueous extract of germinated and ungerminated seeds was analyzed by high-performance liquid chromatography (HPLC) for a comparison of their major compounds. For pregnant treated female mice, no death and no intoxication symptoms have been registered during the test. However, the sprouts’ extract has provoked a significant decrease in fertility, spontaneous abortion, pup’s mortality, and neurobehavioral disorder in offspring. HPLC analysis reveals an increase in total phenolic compound concentration by the process of sprouting.

Objective To summarize published case reports of aortocoronary arteriovenous fistula (ACAVF) after coronary artery bypass grafting surgery (CABG). Background Inadvertent ACAVF is a rare complication following CABG. However, the incidence continues to rise, and its management details and clinical outcomes have not been well described. Methods To identify all published cases of ACAVF following CABG, PubMed, EMBASE, and Scopus were searched through November 2019. We defined ACAVF as inadvertent attachment of the grafting vessel onto a cardiac vein instead of targeted coronary artery. A systematic review was performed to identify the incidence, clinical features, and management outcomes. Results A total of 48 post-CABG ACAVF cases were gathered. Among these patients, the mean age was 61.9 years and 79.2% were men. Most common presenting symptoms were chest pain (60.4%) and dyspnea (27.1%). The average onset of symptoms was 3 years; however, 54.2% of patients developed symptoms within the first year. The majority of cases reported targeted native vessel LAD during CABG (62.5%). Of these cases, 9 (18.8%) were managed conservatively, 8 (16.7%) chose to undergo surgery including ligation of fistula and repeat CABG, and 27 (56.3%) underwent percutaneous closure. Among these patients 13 cases (27.1%) were managed with coil embolization, 5 (10.4%) with balloon embolization, 5 (10.4%) were treated with a covered stent, and 4 (8.3%) used a vascular plug. There were no reported complications following treatment in this group. Conclusions Inadvertent ACAVF are rare following CABG. Percutaneous closure was feasible and safe in treating these patients.

Objective: We describe a case of co-existing Graves disease and struma carcinoid in a woman with an ovarian mass and history of hyperthyroidism.Methods: Patient history, presentation, diagnostic studies, and treatment are described.Results: A 59-year-old female with an antecedent history of hyperthyroidism was scheduled for resection of a 4.1-cm left ovarian mass. Pre-operative labs demonstrated thyroid-stimulating hormone (TSH)

Cardiovascular disease caused by atherosclerosis is the leading cause of mortality associated with type 2 diabetes and metabolic syndrome. Insulin therapy is often needed to improve glycemic control, but it does not clearly prevent atherosclerosis. Upon binding to the insulin receptor (IR), insulin activates distinct arms of downstream signaling. The IR-Akt arm is associated with blood glucose lowering and beneficial effects, whereas the IR-Erk arm might exert less desirable effects. We investigated whether selective activation of the IR-Akt arm, leaving the IR-Erk arm largely inactive, would result in protection from atherosclerosis in a mouse model of metabolic syndrome. The insulin mimetic peptide S597 lowered blood glucose and activated Akt in insulin target tissues, mimicking insulin’s effects, but only weakly activated Erk and even prevented insulin-induced Erk activation. Strikingly, S597 retarded atherosclerotic lesion progression through a process associated with protection from leukocytosis, thereby reducing lesional accumulation of inflammatory Ly6Chi monocytes. S597-mediated protection from leukocytosis was accompanied by reduced numbers of the earliest bone marrow hematopoietic stem cells and reduced IR-Erk activity in hematopoietic stem cells. This study provides a conceptually novel treatment strategy for advanced atherosclerosis associated with metabolic syndrome and type 2 diabetes.

Heart failure (HF) is the leading cause of hospitalization in the USA. Despite advances in pharmacologic management, the incidence of HF is on the rise and survivability is persistently reduced. Sympathetic overdrive is implicated in the pathophysiology of HF, particularly HF with reduced ejection fraction (HFrEF). Tachycardia can be particularly deleterious and thus has spurred significant investigation to mitigate its effects. Various modalities including vagus nerve stimulation, baroreceptor activation therapy, spinal cord stimulation, renal sympathetic nerve denervation, left cardiac sympathetic denervation, and carotid body removal will be discussed. However, the effects of these modalities on tachycardia and its outcomes in HFrEF have not been well-studied. Further studies to characterize this are necessary in the future.

Background IsoPSA is a serum-based assay that predicts prostate cancer (PCa) risk by partitioning isoforms of prostate-specific antigen (PSA) with an aqueous two-phase reagent. Objectives To determine the diagnostic accuracy of IsoPSA in identifying the presence or absence of PCa and the presence of high-grade disease in a contemporary biopsy cohort. Design, setting, and participants Multicenter prospective study of 261 men scheduled for prostate biopsy at five academic and community centers in the USA enrolled between August 2015 and December 2016. Intervention Performance of the IsoPSA assay. Outcome measurements and statistical analysis Discrimination power was evaluated using receiver operating characteristic (ROC) analysis. The outcome of the IsoPSA assay was transformed into risk probability using logistic regression. Decision curve analysis (DCA) was used to compare the net benefit of IsoPSA against other clinical protocols. Results and limitations The overall prevalence was 53% for any PCa and 34% for high-grade PCa. The area under the ROC curve was 0.79 for any cancer versus none and 0.81 for high-grade PCa versus low-grade PCa/benign histology. In this preliminary study, DCA revealed a superior net benefit of IsoPSA against no biopsy, all biopsy, and the modified Prostate Cancer Prevention Trial Risk Calculator 2.0. At a cutoff selected to recommend biopsy, IsoPSA demonstrated a 48% reduction in false-positive biopsies; at a cutoff selected to identity men at low risk of high-grade disease, there was a 45% reduction in the false-positive rate. Conclusion The structure-based IsoPSA assay outperformed concentration-based PSA measurement, and provided a net benefit against other protocols. Once validated, clinical use of IsoPSA could significantly reduce unnecessary biopsies while identifying patients needing treatment. Patient summary The IsoPSA assay outperformed prostate-specific antigen in predicting the overall risk of prostate cancer and the risk of clinically significant cancer in a preliminary study. The IsoPSA assay could assist in determining the need for prostate biopsy for patients.

Purpose Extracorporeal Membrane Oxygenation (ECMO) has been utilized as salvage therapy in patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19. We aim to present our experience with ECMO in a community hospital for minority patients with COVID-19. Methods This is a retrospective analysis of all SARS-CoV2 infected patients who developed ARDS and received ECMO at a tertiary cardiovascular care center between March and August 2020. Patient demographics, data pre- and on-ECMO, hemodynamics, and ventilation parameters were collected. Primary outcome of interest was mortality. Secondary outcomes were length of stay, bleeding requiring transfusion, coagulopathies, infections, and procedural-related complications. Results We identified 10 COVID-19 patients with ARDS treated with ECMO. The mean age was 45 years and 70% were male. The racial composition of the patients consisted of Blacks (30%) and Hispanics (70%). Comorbidities included hypertension (40%), diabetes mellitus (50%), and hyperlipidemia (20%). Eight patients were treated with VV-ECMO, and the remaining patients with VA-ECMO. Hospital-acquired infections including ventilator-associated pneumonia and bacteremia were reported in 50% and 30%, respectively. Hemorrhage requiring transfusion was reported in all 10 patients, with 60% of patients having bleeding from a gastrointestinal source. 70% of patients developed thrombocytopenia, and 20% developed a clot within the ECMO circuit. Coagulation disorders reported, included heparin-induced thrombocytopenia (20%), deep vein thrombosis (30%), and pulmonary embolism (20%). 90% of patients died, and 1 patient was discharged to a long-term acute care hospital (See Table 1 for outcomes). Conclusion Despite using ECMO as rescue therapy, mortality among COVID-19 patients who developed ARDS remained high in minority groups. Further studies are needed to investigate management of COVID-19 related complications.

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Black and Hispanic patients are reported to have higher mortality rates associated with COVID-19 than White patients. There is a paucity of data exploring the effects of extracorporeal membrane oxygenation (ECMO) in COVID-19 patients in respect to race. This study examines differences in outcome between White and Minority COVID-19 patients treated with ECMO in a community hospital. METHODS: This is a retrospective observational study of all patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19 who were treated with ECMO at a tertiary cardiovascular care center between March and December 2020. Patients were stratified into two groups: White and Minority patients. The Minority group was composed entirely of Blacks and Hispanics. Patient demographics, hemodynamics, lab values, treatments, outcomes, and complications were recorded. The primary outcome of interest was mortality. The secondary outcome was rate of ECMO-related complications. RESULTS: We identified 23 consecutive COVID-19 patients with ARDS treated with ECMO, of which 7 (30.5%) were White and 16 (69.5%) were Minorities. 6 White and 13 Minority patients were treated with veno-venous ECMO, with the remaining patients in each group treated with veno-arterial ECMO. There was no significant difference in baseline demographics between groups. Minority patients were found to have a lower mortality rate than White patients (62.5% vs 85.7%, p

Emerging evidence highlighted the essential role played by the microbiota-gut-brain axis in maintaining human homeostasis, including nutrition, immunity, and metabolism. Much recent work has linked the gut microbiota to many psychiatric and neurodegenerative disorders such as depression, schizophrenia, and Alzheimer's disease. Shared gut microbiota alterations or dysbiotic microbiota have been identified in these separate disorders relative to controls. Much attention has focused on the bidirectional interplay between the gut microbiota and the brain, establishing gut dysbiotic status as a critical factor in psychiatric disorders. Still, the antibiotic-like effect of psychotropic drugs, medications used for the treatment of these disorders, on gut microbiota is largely neglected. In this review, we summarize the current findings on the impact of psychotropics on gut microbiota and how their antimicrobial potency can trigger dysbiosis. We also discuss the potential therapeutic strategies, including probiotics, prebiotics, and fecal transplantation, to attenuate the dysbiosis related to psychotropics intake.

Objective An increasing emphasis on preventive medicine has been supported by the recent reforms in United States health care system. Majority of the patients seen in vascular surgery clinics are elderly with more extensive medical comorbidities compared to the general population. Thus, these patients would be expected at higher risk for common malignant pathologies such as colon, breast and cervical cancer, and nonmalignant diseases such as diabetic retinopathy. This study looked at the screening compliance of vascular patients compared to data provided by Centers for Disease Control on the national and state levels. Methods The office records of 851 consecutive patients seen in Brooklyn and Staten Island vascular clinics were examined. We queried patients regarding their last colonoscopy, diabetic eye exams, recent mammograms, and Pap smears. Our patient screening compliance was compared between the two clinics as well as to the national and New York state data provided by Centers for Disease Control. Compliance with regard to patient’s age was also examined. Results Patients referred to the Staten Island office have a better colonoscopy compliance compared to the Brooklyn office ( P = .0001) and the national Centers for Disease Control average ( P = .026). Compliance for mammography and cervical cancer screening was higher in Staten Island office compared to the Brooklyn office ( P = .0001, P Conclusion Patients in vascular clinics in an urban setting had better adherence to screening protocol than the national and state average, with the exception of female patients for colonoscopy in our Brooklyn vascular office. There exists variability in both patient populations based on sub-specific locality and demographics including socioeconomic status. Overall, however patients in Staten Island had better compliance and adherence to the screening protocol than Brooklyn vascular clinic.

Background: Fluid management remains a major challenge of hemodialysis (HD) care, with serious implications for morbidity and mortality. Intradialytic fluid management is typically guided by blood pressure, an indirect resultant of hemodynamics status. Direct measurements of hemodynamic parameters may improve cardiovascular outcomes by providing rational bases for intervention. We compare stroke volume (SV) measurements using a noninvasive, regional biompedance cardiography device (NiCaS) with Doppler echocardiography (Echo) in HD setting. Methods: Stroke volumes were simultaneously measured using the devices in 17 patients receiving maintenance HD. Measurements were made during 2 weekly HD treatments, and twice within each HD treatment during the first and last hour of each treatment, for a total of 64 SV measurements. Agreement between devices was assessed using linear regression, a Pearson's correlation coefficient, and a Bland-Altman plot all adjusted for repeated measures within patients. Results: Echo and NiCaS SV mean and 95% CIs were 58.0 (50.1, 65.8) and 56.7 (49.4, 64.0) mL, respectively. NiCaS SV correlated strongly with Echo SV during the first and last hours of treatments (r = 0.93, P

We recently reported that cholesterol crystals form in hepatocyte lipid droplets (LDs) in human and experimental nonalcoholic steatohepatitis. Herein, we assigned WT C57BL/6J mice to a high-fat (15%) diet for 6 months, supplemented with 0%, 0.25%, 0.5%, 0.75%, or 1% dietary cholesterol. Increasing dietary cholesterol led to cholesterol loading of the liver, but not of adipose tissue, resulting in fibrosing steatohepatitis at a dietary cholesterol concentration of ≥0.5%, whereas mice on lower-cholesterol diets developed only simple steatosis. Hepatic cholesterol crystals and crown-like structures also developed at a dietary cholesterol concentration ≥0.5%. Crown-like structures consisted of activated Kupffer cells (KCs) staining positive for NLRP3 and activated caspase 1, which surrounded and processed cholesterol crystal-containing remnant LDs of dead hepatocytes. The KCs processed LDs at the center of crown-like structures in the extracellular space by lysosomal enzymes, ultimately transforming into lipid-laden foam cells. When HepG2 cells were exposed to LDL cholesterol, they developed cholesterol crystals in LD membranes, which caused activation of THP1 cells (macrophages) grown in coculture; upregulation of TNF-alpha, NLRP3, and interleukin 1beta (IL1β) mRNA; and secretion of IL-1beta. In conclusion, cholesterol crystals form on the LD membrane of hepatocytes and cause activation and cholesterol loading of KCs that surround and process these LDs by lysosomal enzymes.

Objective The impact of the Survival Sepsis Campaign in patients with heart failure (HF) and sepsis is unknown. Furthermore, there is limited data on the impact of age on clinically relevant outcomes in this population. Methods This retrospective cohort study included 618 patients with HF that developed sepsis. Based on age, patients were stratified into the elderly (age ≥75 years), middle-aged (55-74 years), and young adults (18-54 years). Primary outcomes included all-cause in-hospital mortality. Secondary outcomes include the development of pulmonary edema requiring interventions (diuretics vs. mechanical ventilation), cardiogenic shock, post-admission acute kidney injury (AKI), hospital length of stay (LOS), and 30-day HF-related readmission rate. Results chronic comorbidities such as coronary artery disease, hypertension, atrial fibrillation, and HF with preserved ejection fraction were more common in the elderly, while end-stage renal disease and HF with reduced ejection fraction were most likely present in young adults (See table 1).Predictors of poor outcomes such as quick sequential organ failure assessment (qSOFA) (p=0.1752), systemic inflammatory response syndrome (SIRS) (p=0.1186), and acute decompensated heart failure national registry (ADHERE) (p=0.1465) were similar among the three age groups. However, younger aged patients were most likely to have elevated NT-pro BNP, lactic acid, total bilirubin, and low albumin. The Surviving Sepsis Campaign Bundle (i.e., broad-spectrum antimicrobials and intravenous crystalloids) was equally implemented in all three age groups (p=NS). Outcomes for the elderly, middle age, and young adult population, in-hospital mortality was 33% vs. 30% vs. 24%, p=0.3881, respectively. The elderly had the lowest incidence of cardiogenic shock (p Conclusion Elderly patients with HF that develop sepsis had proportionally higher mortality (33% vs. 30% vs. 24%) despite having fewer predictors of mortality, less in-hospital complications, and shorter LOS than other age groups. These findings suggest that the generalization of the surviving sepsis campaign in patients with HF and sepsis may be deleterious. It should be individualized based on the age group.