Citations

Background: Lung ultrasound detects pulmonary congestion as B-lines at rest, and more frequently, during exercise stress echocardiography (ESE). Methods: We performed ESE plus lung ultrasound (4-site simplified scan) in 4392 subjects referred for semi-supine bike ESE in 24 certified centers in 9 countries. B-line score ranged from 0 (normal) to 40 (severely abnormal). Five different populations were evaluated: control subjects (n=103); chronic coronary syndromes (n=3701); heart failure with reduced ejection fraction (n=395); heart failure with preserved ejection fraction (n=70); ischemic mitral regurgitation ≥ moderate at rest (n=123). In a subset of 2478 patients, follow-up information was available. Results: During ESE, B-lines increased in all study groups except controls. Age, hypertension, abnormal ejection fraction, peak wall motion score index, and abnormal heart rate reserve were associated with B-lines in multivariable regression analysis. Stress B lines (hazard ratio, 2.179 [95% CI, 1.015–4.680]; P =0.046) and ejection fraction <50% (hazard ratio, 2.942 [95% CI, 1.268–6.822]; P =0.012) were independent predictors of all-cause death (n=29 after a median follow-up of 29 months). Conclusions: B-lines identify the pulmonary congestion phenotype at rest, and more frequently, during ESE in ischemic and heart failure patients. Stress B-lines may help to refine risk stratification in these patients. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT 03049995.

Angioinvasive fungal infections of the cerebral vasculature often lead to significant morbidity and mortality. High clinical suspicion and early antifungal therapy could improve outcomes. We describe the fatal case of a patient with a rapidly enlarging cavernous carotid aneurysm due to angioinvasive fungus. This case highlights the challenges in diagnosis and management of this condition.

AbstractBackgroundE3805 (CHAARTED) is a phase 3 trial demonstrating improved survival for men with metastatic hormone‐sensitive prostate cancer (mHSPC) randomized to treatment with docetaxel (D) and androgen‐deprivation therapy (ADT) versus ADT alone. We assessed the association of baseline body mass index (BMI) and metformin exposure with quality of life (QOL) and prostate cancer outcomes including survival in patients enrolled in the CHAARTED study.MethodsWe performed a posthoc exploratory analysis of the CHAARTED trial of men with mHSPC randomized to treatment with ADT with or without D between 2006 and 2012. Cox proportional hazards models and Kruskal–Wallis test were used to evaluate the association between BMI with QOL and prostate cancer outcomes and between metformin exposure and survival.ResultsIn 788 of 790 enrolled patients with prospectively recorded baseline BMI and metformin exposure status, lower BMI was not associated with survival, but was associated with high volume disease (p < 0.0001) and poorer baseline QOL on functional assessment of cancer therapy–prostate (p = 0.008). Only 68 patients had prevalent metformin exposure at baseline in the CHAARTED trial. Four groups were identified: ADT + D + metformin (n = 39); ADT + D (n = 357); ADT + metformin (n = 29); and ADT alone (n = 363). Baseline clinicopathologic characteristics were similar between groups. In this small exploratory multivariable analysis, metformin exposure was not associated with survival (hazard ratio: 1.15; 95% confidence interval: 0.81–1.63, p = 0.44).ConclusionsThere was no link between baseline BMI and survival, but lower baseline BMI was associated with features of greater cancer burden and poorer QOL.

Background: Vascular endothelial growth factor (VEGF) C156S is an engineering variant of VEGF-C that has the potential to promote lymphangiogenesis, activating on VEGF receptor (VEGFR) 3, without promoting angiogenesis (i.e., not acting on VEGFR-2). We conducted a systematic review of publications assessing the use of this growth factor in lymphedema treatment. We hypothesized that VEGF-C156S specificity for VEGFR-3 was an important differential for the lymphangiogenesis promoted by it. Methods and Results: We conducted a comprehensive systematic review of the published literature on PubMed/Medline, Embase, and Cochrane Clinical Answers. Eligibility criteria included articles reporting data on the use of VEGF-C156S in lymphedema treatment. We excluded articles that investigated physiology action of VEGF-C156S and articles that focused on other therapies. From 304 potential articles found in the literature, four studies fulfilled the study eligibility criteria. To date, all studies about this growth factor have been experimental. The effect of VEGF-C156 on lymph node transfer was investigated in half of the experiments. Interestingly, delivery of VEGF-C156S was mostly performed through viral gene transfer, but injection (subcutaneously or intravenously) of it as a protein (liposomal or nonliposomal) was also investigated by one author to assess drug bioavailability. Conclusions: Although authors reported promotion of lymphangiogenesis, VEGF-C156S was correlated with lymphatic hyperplasia or nonstatistically significant lymphangiogenesis compared with controls. Scientific evidence about the use of VEGF-C156S in lymphedema treatment is still limited. However, authors have shown that its lymphangiogenic effect is inferior to VEGF-C.

Stenting of the intracranial venous sinuses has shown promising results in patients who are refractory to medical treatment of idiopathic intracranial hypertension (IIH). Among the reported complications associated with this procedure, in-stent thrombosis is an unreported one. We present a case of cerebral sinus thrombosis during endovascular treatment of IIH. A 33-year-old man with multiple comorbidities was presented with non-specific vision changes and headaches. Initial workup revealed a diagnosis of idiopathic intracranial hypertension which was treated medically but with no improvement. Therefore, cerebral sinus stenting was pursued. During the procedure, an in-stent thrombus was identified which was retrieved mechanically and was sent for histological and immunohistochemical evaluation. The retrieved thrombus was predominantly composed of RBCs (57.8%) followed by fibrin (30.78%), platelet (6.4%), and WBCs (5.95%), with high expression of CitH3 (neutrophil extra cellular traps specific marker) (10.9%), and CD66 (11.35%).

Abstract MSC (a.k.a. mesenchymal stem cell or medicinal signaling cell) cell therapies show promise in decreasing mortality in acute respiratory distress syndrome (ARDS) and suggest benefits in treatment of COVID-19-related ARDS. We performed a meta-analysis of published trials assessing the efficacy and adverse events (AE) rates of MSC cell therapy in individuals hospitalized for COVID-19. Systematic searches were performed in multiple databases through November 3, 2021. Reports in all languages, including randomized clinical trials (RCTs), non-randomized interventional trials, and uncontrolled trials, were included. Random effects model was used to pool outcomes from RCTs and non-randomized interventional trials. Outcome measures included all-cause mortality, serious adverse events (SAEs), AEs, pulmonary function, laboratory, and imaging findings. A total of 736 patients were identified from 34 studies, which included 5 RCTs (n = 235), 7 non-randomized interventional trials (n = 370), and 22 uncontrolled comparative trials (n = 131). Patients aged on average 59.4 years and 32.2% were women. When compared with the control group, MSC cell therapy was associated with a reduction in all-cause mortality (RR = 0.54, 95% CI: 0.35-0.85, I 2 = 0.0%), reduction in SAEs (IRR = 0.36, 95% CI: 0.14-0.90, I 2 = 0.0%) and no significant difference in AE rate. A sub-group with pulmonary function studies suggested improvement in patients receiving MSC. These findings support the potential for MSC cell therapy to decrease all-cause mortality, reduce SAEs, and improve pulmonary function compared with conventional care. Large-scale double-blinded, well-powered RCTs should be conducted to further explore these results.

Objectives: Traditional hospital at home models often have high patient experience scores. The purpose of this study is to look at the patient experience of a new virtual hybrid model of hospital at home called Advanced Care at Home. Methods: Patients in Mayo Clinic’s Advanced Care at Home program received a survey via email from 1 January–31 May 2021. Each survey consisted of 20 questions divided into 18 multiple-choice and two open-ended questions. Results: Ninety-nine surveys were sent and 41 partially or completely finished surveys were returned for a response rate of 41.4%. Patients responded positively, denoted by answering “strongly agree or somewhat agree,” with regard to the ability to reach the team right away 100% of the time, being kept informed 92% of the time, the command center responding promptly to their needs 95% of the time, the team providing comfort and support 98% of the time, feeling comfortable with interacting with their provider by phone or tablet 95% of the time, the ease of use from the equipment 97% of the time, the virtual and in-person staff working well together 98% of the time, the staff treating patients with courtesy and respect 100% of the time, and the ease of understanding the discharge process and feeling ready to leave the program 100% of the time. All providers received positive responses on listening ⩾88% of the time. Patients gave a top rating in likelihood to recommend the program 100% of the time. Conclusion: Overall, the Advanced Care at Home model of hospital at home was highly recommended by patients. Patients scored the program high on responsiveness, staff engagement and communication, ease of equipment use, and readiness for discharge, strengthening the overall confidence in this novel program.

Neurodevelopmental disorders are associated with metabolic pathway imbalances; however, most metabolic measurements are made peripherally, leaving central metabolic disturbances under-investigated. Cerebrospinal fluid obtained intraoperatively from children with autism spectrum disorder (ASD, n = 34), developmental delays (DD, n = 20), and those without known DD/ASD (n = 34) was analyzed using large-scale targeted mass spectrometry. Eighteen also had epilepsy (EPI). Metabolites significantly related to ASD, DD and EPI were identified by linear models and entered into metabolite–metabolite network pathway analysis. Common disrupted pathways were analyzed for each group of interest. Central metabolites most involved in metabolic pathways were L-cysteine, adenine, and dodecanoic acid for ASD; nicotinamide adenine dinucleotide phosphate, L-aspartic acid, and glycine for EPI; and adenosine triphosphate, L-glutamine, ornithine, L-arginine, L-lysine, citrulline, and L-homoserine for DD. Amino acid and energy metabolism pathways were most disrupted in all disorders, but the source of the disruption was different for each disorder. Disruption in vitamin and one-carbon metabolism was associated with DD and EPI, lipid pathway disruption was associated with EPI and redox metabolism disruption was related to ASD. Two microbiome metabolites were also detected in the CSF: shikimic and cis-cis-muconic acid. Overall, this study provides increased insight into unique metabolic disruptions in distinct but overlapping neurodevelopmental disorders.

Background Patients with mild to severe chronic systemic disease undergoing low-risk procedures are often hospitalized for observation. The Care Hotel is a novel virtual medicine hybrid model of care that offers patients a comfortable, out of hospital environment where they can receive both in-person and virtual care after a surgery or procedure. This study aimed to analyze if virtual hybrid post-procedure care in a hotel could be both conducted on and accepted by patients, even those with moderate to severe chronic diseases. Methods This retrospective cohort study was conducted between July 23, 2020 and June 4, 2021 at Mayo Clinic in Florida, a 306-bed community academic hospital. We collected the sex, age, race, ethnicity, acceptance rate, ASA score, and primary procedure of patients using the Care Hotel. Results Out of 392 patients, 272 (69.4%) opted for care in the program. Median patient age was 61.5 years, 59.56% were males, and 86.40% were white. We found that 50.37% had an ASA score of 2 and 43.4% had an ASA score of 3. Ten different surgical specialties were able to utilize the Care Hotel for care in 47 different procedure types. Urology had the most patients (n=70, 25.7%). Post-electrophysiologic procedures were the most common procedures (n=39, 14.3%). Conclusion Our virtual hybrid Care Hotel program was widely accepted by patients and could care for a multitude of post-operative procedures. Additionally, this novel program can care for patients with both mild and severe systemic diseases.