tbuckley/cabot-search huggingface dataset:
Engineered Cell‐Secreted Extracellular Matrix Modulates Cell Spheroid Mechanosensing and Amplifies Their Response to Inductive Cues for the Formation of Mineralized Tissues
Authors: Tomas Gonzalez‐Fernandez, Alejandro J. Tenorio, Augustine M. Saiz Jr, J. Kent Leach
Journal: Advanced Healthcare Materials (2021)

The clinical translation of mesenchymal stromal cell (MSC)-based therapies remains challenging due to rapid cell death and poor control over cell behavior. Compared to monodisperse cells, the aggregation of MSCs into spheroids increases their tissue-forming potential by promoting cell-cell interactions. However, MSCs initially lack engagement with an endogenous extracellular matrix (ECM) when formed into spheroids. Previously the instructive nature of an engineered, cell-secreted ECM is demonstrated to promote survival and differentiation of adherent MSCs. Herein, it is hypothesized that the incorporation of this cell-secreted ECM during spheroid aggregation would enhance MSC osteogenic potential by promoting cell-matrix and cell-cell interactions. ECM-loaded spheroids contained higher collagen and glycosaminoglycan content, and MSCs exhibited increased mechanosensitivity to ECM through Yes-associated protein (YAP) activation via integrin α2β1 binding. ECM-loaded spheroids sustained greater MSC viability and proliferation and are more responsive to soluble cues for lineage-specific differentiation than spheroids without ECM or loaded with collagen. The encapsulation of ECM-loaded spheroids in instructive alginate gels resulted in spheroid fusion and enhanced osteogenic differentiation. These results highlight the clinical potential of ECM-loaded spheroids as building blocks for the repair of musculoskeletal tissues.
Recurrent Paravalvular Leak Following Mitral Valve Replacement
Authors: Badar Patel, Musa A. Sharkawi, Pinak B. Shah
Journal: JAMA Cardiology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Abstract 11503: Mindfulness is Inversely Associated with Psychological Symptoms in Long-Term Cardiac Arrest Survivors
Authors: Alex Presciutti, Jonathan Greenberg, Ethan Lester, Mary M Newman, Jonathan Elmer, Jonathan Shaffer, Ana-maria Vranceanu, Sarah M Perman
Journal: Circulation (2021)

Introduction: We sought to identify correlates with psychological symptoms in long-term cardiac arrest (CA) survivors. Mindfulness, or nonjudgmental awareness of the present moment, is a modifiable protective factor against psychological symptoms in various clinical populations and could be a potential treatment target for CA survivors. Methods: We conducted a longitudinal survey study between 10-11/2019 (baseline) and 10-11/2020 (1-year follow-up) with long-term CA survivor members of the Sudden Cardiac Arrest Foundation. We collected demographic and CA characteristics at baseline. At both timepoints, we assessed posttraumatic stress symptoms (PTS) through the PTSD Checklist-5 (PCL-5) and depression and anxiety symptoms through the Patient Health Questionnaire-4 (PHQ-4). At follow-up, we assessed mindfulness through the Cognitive and Affective Mindfulness Scale-Revised (CAMS-R). We used adjusted linear regression to predict 1-year PCL-5 and PHQ-4 scores, with particular consideration of the CAMS-R as a cross-sectional correlate of outcome. Results: We included 129 CA survivors (mean age: 52 years, 52% male, 98% white). At 1-year follow-up, in adjusted models, CAMS-R (β: -0.35, p &lt;0.001) and baseline PCL-5 scores (β: 0.56, p &lt;0.001) were associated with 1-year PCL-5 scores. CAMS-R (β: -0.34, p &lt;0.001) and baseline PHQ-4 scores were associated with 1-year PHQ-4 scores (β: 0.37, p&lt;0.001). Conclusion: Mindfulness was inversely associated with psychological symptoms in long-term CA survivors. Future studies should examine the longitudinal relationship of mindfulness and psychological symptoms after CA.
Abstract 16643: Pacemaker For First Degree AV Block Without Bradycardia: Pseudo-pacemaker Syndrome
Authors: Muhammad Hamza Saad Shaukat, Fouad Khalil, Mamoon Ahmed, Marian S Petrasko
Journal: Circulation (2021)

Case Presentation: An 86 year old man underwent PCI of distal LAD for severe single vessel coronary artery disease identified after a high risk pharmacologic nuclear stress test (evaluation of exertional fatigue prior to abdominal aortic aneurysm surgical repair). ECHO was consistent with preserved LVEF (60-65%), moderate concentric LVH and mild left atrial enlargement. Less than a week after PCI, he presented to the emergency department for NYHA III dyspnea and fatigue. The patient was not taking any negative chronotropic medications. CT angiography of the chest excluded pulmonary edema, pneumonia and pulmonary embolism; repeat limited ECHO was unchanged. EKG showed first degree AV block (PR 400ms, figure 1). Severely prolonged PR interval with otherwise-unexplained exertional symptoms raised suspicion for pseudo-pacemaker syndrome. In the absence of an alternative cause of declining exertional tolerance, a dual chamber pacemaker with short programmed AV delay (&lt;200ms) was implanted. The patient reported resolution of exertional fatigue and dyspnea on one-month followup. Discussion: Pseudo-pacemaker syndrome is a rare, infrequently reported, complication of first degree AV block with severely prolonged PR&gt;300ms. P-wave at the end of the preceding T-wave suggests AV dyssynchrony (arrowhead, figure 1). Left atrial contraction against a closed mitral valve led to loss of atrial contribution to cardiac output, and elevated left atrial pressure. These changes, accentuated by physiologic increase in heart rate on exertion, most likely caused symptoms in this patient. It is interesting that AV dyssynchrony in pacemaker syndrome is caused by the pacemaker (VVI pacing) whereas the AV dyssynchrony in pseudo-pacemaker syndrome from severely prolonged PR interval is treated with a pacemaker. In the appropriate clinical picture, it is an indication for dual-chamber pacemaker implantation for first degree AV block without bradycardia or pauses.
Guidance on cow’s milk allergy may be fuelling overdiagnosis in infants, study finds
Authors: Elisabeth Mahase
Journal: BMJ (2021)

<h3>Background</h3> Monotherapy with immune checkpoint blockade is ineffective for patients (pts) with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). This study investigates whether the combination of trametinib (T) with durvalumab (D) can alter the immune tumor microenvironment (TME) by successfully priming and activating T-cells. <h3>Methods</h3> Open-label, single-center, phase II trial with primary endpoint of immune-related response rate for combination of T+D in refractory MSS mCRC pts (NCT03428126). T is 2 mg/day orally starting 1 week prior to D, which is given 1500 mg intravenously every 4 weeks. Simon 2-stage design used to enroll 29 pts into first stage, requiring a response in two or more pts to proceed to stage 2. Tumor biopsies were collected at baseline (BL) and early on-treatment (OT) at week 4. <h3>Results</h3> Twenty nine treated pts include 48% females, median age 48 years (range 28–75), and median prior therapies 2 (range 1–5). No grade (G) 4 or 5 treatment-related adverse events (TRAE). The most common TRAE of any grade was acneiform rash, 17% being G3. One of 29 pts had confirmed partial response (PR) lasting 9.3 months (mo) for an overall response rate of 3.4%. Seven pts had stable disease (SD) and five pts (1 PR, 4 SD) demonstrated decrease in total carcinoembryonic antigen ng/mL (best percentage reduction: 94%, 95%, 42%, 34%, and 22%, respectively). Median progression-free survival was 3.2 mo (range 1.1–9.3 months). Three pts with both liver and lung metastases demonstrated discrepant responses in which clinical benefit was present in the lung metastases but not liver metastases. Comparison of BL and 4-week OT tumor tissue flow cytometry demonstrated no changes in T-cell infiltration but upregulation expression of PD-1 and Tim3 on CD8 T cells. However, expression of PD-1 and Tim3 as single markers and as coexpressed markers was observed to increase OT relative to BL (p=0.03, p=0.06 and p=0.06, respectively). <h3>Conclusions</h3> T+D demonstrated acceptable tolerability in pts with refractory MSS mCRC. The response rate in the first stage of the study did not meet efficacy criteria to proceed to the second stage. Specific site of metastatic disease may impact outcomes in novel immunotherapy combination trials. <h3>Trial registration number</h3> NCT03428126.
Detection of Subclinical Cardiovascular Disease by Cardiovascular Magnetic Resonance in Lymphoma Survivors
Authors: Nikki van der Velde, Cécile P.M. Janus, Daniel J. Bowen, H. Carlijne Hassing, Isabella Kardys, Flora E. van Leeuwen, Cynthia So-Osman, Remi A. Nout, Olivier C. Manintveld, Alexander Hirsch
Journal: JACC CardioOncology (2021)

Long-term survivors of Hodgkin lymphoma (HL) and mediastinal non-Hodgkin lymphoma experience late adverse effects of radiotherapy and/or anthracycline-containing chemotherapy, leading to premature cardiovascular morbidity and mortality. The aim of this study was to identify markers for subclinical cardiovascular disease using cardiovascular magnetic resonance (CMR) in survivors of HL and non-Hodgkin lymphoma. CMR was performed in 80 lymphoma survivors treated with mediastinal radiotherapy with or without anthracyclines, and results were compared with those among 40 healthy control subjects matched for age and sex. Of the 80 lymphoma survivors, 98% had histories of HL, the mean age was 47 ± 11 years, and 54% were male. Median radiotherapy dose was 36 Gy (interquartile range: 36-40 Gy), and radiotherapy was combined with anthracyclines in 70 lymphoma survivors (88%). Mean time between diagnosis and CMR was 20 ± 8 years. Significantly lower left ventricular (LV) ejection fraction (53% ± 5% vs 60% ± 5%; P < 0.001) and LV mass (47 ± 10 g/m2 vs 56 ± 8 g/m2; P < 0.001) and higher LV end-systolic volume (37 ± 8 mL/m2 vs 33 ± 7 mL/m2; P = 0.013) were found in lymphoma survivors. LV global strain parameters were also significantly worse in lymphoma survivors (P < 0.02 for all). Native myocardial T1 was significantly higher in lymphoma survivors compared with healthy control subjects (980 ± 33 ms vs 964 ± 25 ms; P = 0.007), and late gadolinium enhancement was present in 11% of the survivors. Long-term lymphoma survivors have detectable changes in LV function and native myocardial T1 on CMR. Further longitudinal studies are needed to assess the implication of these changes in relation to treatment and clinical outcome.
67P Sintilimab, doxorubicin and ifosfamide (AI) as first-line treatment in patients with advanced soft tissue sarcoma: A single-arm phase II trial
Authors: Z. Luo, X. Liu, X. Zhang, X. He, S. Zhang, W. Yan, Y. Chen, C. Wang, Y. Xu, L. Yu, J. Wang
Journal: Annals of Oncology (2021)
Abstract 11532: Variation in Coronary Angiography Use in Out-of-Hospital Cardiac Arrest
Authors: Patrick Dale, Rohan Khera, Brown Siobhan, Ahamed Idris, Mark S Link, Purav Mody
Journal: Circulation (2021)

Introduction: Current patterns of use of coronary angiography (CAG) among out-of-hospital cardiac arrest (OHCA) patients based on ST segment elevation (STE) on post-resuscitation ECG are not well described. Methods: Using data from the Continuous Chest Compressions trial between 2011 and 2016, we identified OHCA patients who survived to hospitalization. We examined rates of CAG across different trial clusters in the overall cohort and among pre-specified subgroups with presumed cardiac etiology of arrest e.g. initial shockable rhythm and STE on presenting ECG. Results: Of 26,148 OHCA patients across 49 trial clusters, 5608 survived to hospital admission. The mean age of patients was 64 years, with 65% men and 43% with initial shockable rhythm. Among patients with initial shockable rhythm 44% had STE on initial ECG compared with 18% of patients with initial non-shockable rhythm. Use of CAG was significantly higher in patients presenting with STE compared with no STE on initial ECG irrespective of initial rhythm: 70% vs. 31%, p&lt;0.001 for initial shockable rhythm and 28% vs. 5%, p&lt;0.001 for initial non-shockable rhythm. In the overall cohort, there was significant variation in CAG use across trial clusters ranging from 4% - 41% of patients within a trial cluster receiving CAG ( Figure ). This variation persisted among pre-specified subgroups with the proportion of patients within a trial cluster receiving CAG ranged from 11% - 75% for patients with initial shockable rhythm, 0% to 19% with initial non-shockable rhythm, 16% - 82% with STE, 2% - 28% without STE and 0% - 63% in patients with initial shockable rhythm and no STE on presenting ECG ( Figure ). Conclusion: There is a higher use of CAG in STE and shockable cardiac arrest, consistent with presumed cardiac etiology of arrest; however, there is large variation in the use of CAG across sites, even among patients with a presumed cardiac etiology of cardiac arrest suggesting challenges with interpretation of current guidelines.
Publisher Correction: Significant association of cutaneous adverse events with hydroxyurea: results from a prospective non-interventional study in BCR-ABL1-negative myeloproliferative neoplasms (MPN) - on behalf of the German Study Group-MPN
Authors: Frank Stegelmann, Kai Wille, Hannah Busen, Christiane Fuchs, Stefanie Schauer, Parvis Sadjadian, Tatjana Becker, Vera Kolatzki, Hartmut Döhner, Rudolf Stadler, Konstanze Döhner, Martin Griesshammer
Journal: Leukemia (2021)
Endoscopic transcecal appendectomy: a new endotherapy for appendiceal orifice lesions
Authors: Linjie Guo, Liansong Ye, Yilong Feng, Johannes Bethge, Juliana Yang, Stefan Schreiber, Bing Hu
Journal: Endoscopy (2021)

Endoscopic transcecal appendectomy (ETA) has been reported as a minimally invasive alternative procedure for lesions involving the appendiceal orifice. The aim of this case series study was to evaluate the feasibility, safety, and effectiveness of ETA for lesions at the appendiceal orifice.This retrospective study included consecutive patients with appendiceal orifice lesions who underwent ETA between December 2018 and March 2021. The primary outcome was technical success. The secondary outcomes included postoperative adverse events, postoperative hospital stay, and recurrence.13 patients with appendiceal orifice lesions underwent ETA during the study period. The median lesion size was 20 mm (range 8-50). Lesions morphologies were polypoid lesions (n = 5), laterally spreading tumors (n = 4), and submucosal lesions (n = 4). Technical success with complete resection was achieved in all 13 cases. There were no postoperative bleeding, perforation, or intra-abdominal abscess. The median length of hospital stay after ETA was 8 days (range 6-18). There was no tumor recurrence during a median follow-up of 17 months (range 1-28).ETA is feasible, safe, and effective for complete resection of appendiceal orifice lesions. Larger, multicenter, prospective studies are needed to further assess this technique.
Can early measles vaccination control both measles and respiratory syncytial virus infections?
Authors: Lien Anh Ha Do, Zheng Quan Toh, Paul Vincent Licciardi, Edward Kim Mulholland
Journal: The Lancet Global Health (2021)

Measles virus and respiratory syncytial virus (RSV) are two important global health pathogens causing substantial morbidity and mortality worldwide. The current measles vaccination schedule has the first dose given at 9-12 months of age and the second dose given at 15-18 months of age. Measles outbreaks have been associated with an increase in severe RSV infections in children younger than 6 months, probably as a result of measles-induced immunosuppression. A resurgence in measles cases was already occurring before the COVID-19 pandemic, which has affected global immunisation programmes, resulting in millions of children, mostly in low-income and middle-income countries (LMICs), missing out on their measles vaccine. This will leave many children living in the most vulnerable of circumstances highly susceptible to measles and RSV infections when current COVID-19 public health control measures are lifted. This Viewpoint discusses these issues and highlights the need for urgent action to address this looming crisis. The use of early measles vaccination at 4 months of age could be an effective strategy to prevent severe morbidity and death from both measles and RSV infections in many LMICs.
Effect of Concurrent Chemoradiotherapy With Nedaplatin vs Cisplatin on the Long-term Outcomes of Survival and Toxic Effects Among Patients With Stage II to IVB Nasopharyngeal Carcinoma
Authors: Qing-Nan Tang, Li-Ting Liu, Bin Qi, Shan-Shan Guo, Dong-Hua Luo, Rui Sun, Xue-Song Sun, Dong-Ping Chen, Ling Guo, Hao-Yuan Mo, Pan Wang, Sai-Lan Liu, Yu-Jing Liang, Xiao-Yun Li, Zhen-Chong Yang, Qiu-Yan Chen, Hai-Qiang Mai, Lin-Quan Tang
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Nedaplatin-based concurrent chemoradiotherapy (CCRT) regimen at 2 years was noninferior to cisplatin-based regimen in patients with locoregional, stage II to IVB nasopharyngeal carcinoma (NPC) and was associated with fewer late adverse events, but longer-term outcomes and toxicity are unclear. <h3>Objective</h3> To evaluate the 5-year outcomes and late toxicity profile of nedaplatin-based CCRT in patients with locoregional, stage II to IVB NPC. <h3>Design, Settings, and Participants</h3> This 5-year follow-up secondary analysis of an open-label, noninferiority, multicenter randomized clinical trial enrolled patients with nonkeratinizing stage II to IVB NPC between January 16, 2012, and July 16, 2014, with a median follow-up duration of 78 months (IQR, 3-99 months). Data analysis was conducted from November 10, 2020, to July 8, 2021. <h3>Interventions</h3> Patients were randomly assigned (1:1) to receive nedaplatin (100 mg/m<sup>2</sup>)– or cisplatin (100 mg/m<sup>2</sup>)–based chemotherapy every 3 weeks for 3 cycles concurrently with intensity-modulated radiotherapy. <h3>Main Outcomes and Measures</h3> The primary end point was progression-free survival (PFS). Secondary end points were overall survival, distant metastasis–free survival, and locoregional relapse–free survival. <h3>Results</h3> A total of 402 eligible participants were enrolled (median [IQR] age, 45 [18-65] years; 302 [75.1%] male). Patients were randomly assigned to receive nedaplatin- or cisplatin-based CCRT (n = 201 for each): 196 patients (97.5%) started nedaplatin-based CCRT and 197 patients (98.0%) started cisplatin-based CCRT. Intention-to-treat analysis demonstrated a 5-year progression-free survival rate of 81.4% (95% CI, 75.9%-86.9%) for the cisplatin group and 79.8% (95% CI, 74.1%-85.5%) for nedaplatin group, with a difference of 1.6% (95% CI, −6.3% to 9.5%;<i>P</i> = .002 for noninferiority). No significant survival differences were observed between the cisplatin and nedaplatin groups for 5-year overall survival (89.4% vs 88.8%,<i>P</i> = .63), distant metastasis–free survival (85.9% vs 90.4%,<i>P</i> = .17), and locoregional relapse–free survival (92.6% vs 89.6%,<i>P</i> = .17) rates. The cisplatin group had a higher incidence of grade 3 and 4 auditory toxic effects than the nedaplatin group (35 [17.7%] vs 21 [10.5%],<i>P</i> = .04). <h3>Conclusions and Relevance</h3> In this secondary analysis of a randomized clinical trial, long-term analysis confirmed that nedaplatin-based CCRT could be regarded as an alternative doublet treatment strategy to cisplatin-based CCRT in stage II to IVB NPC. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT01540136
Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease
Authors: Satoshi Kubo, Jill M. Fritz, Hayley M. Raquer-McKay, Rhea Kataria, Ivan Vujkovic-Cvijin, Ahmad Al-Shaibi, Yikun Yao, Lixin Zheng, Juan Zou, Alex D. Waldman, Xinyi Jing, Taylor K. Farley, Ann Y. Park, Andrew J. Oler, Adrian K. Charles, Melanie Makhlouf, Eman H. AbouMoussa, Reem Hasnah, Luis R. Saraiva, Sundar Ganesan, Abdulrahman Ahmed Al-Subaiey, Helen Matthews, Emilio Flano, Hyun Hee Lee, Alexandra F. Freeman, Asena Pınar Sefer, Ersin Sayar, Erkan Çakır, Elif Karakoc-Aydiner, Safa Baris, Yasmine Belkaid, Ahmet Ozen, Bernice Lo, Michael J. Lenardo
Journal: Nature Immunology (2021)
Recurrent appendicitis following successful drainage of appendicular abscess in adult without interval appendectomy during COVID-19. Prospective cohort study
Authors: Tamer A.A.M. Habeeb, Abdulzahra Hussain, Francisco Schlottmann, Mohammad Kermansaravi, Alberto Aiolfi, Ivan Matic, Osama Abdelazez, Said mohamed negm, Muhammad Ali Baghdadi, Mahmoud Abdou yassin, Ahmed M. Sallam, Hatem Mohammad, Fady Mehaney Habib, Mohamed I. Abdelhamid, Mohamed Farouk Amin
Journal: International Journal of Surgery (2021)