bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Requirement of Phosphatidylinositol(3,4,5)Trisphosphate in Phosphatidylinositol 3-Kinase-Induced Oncogenic Transformation
Authors: Denley Adam , Gymnopoulos Marco , Kang Sohye , Mitchell Christina , Vogt Peter K.
Published: January 2024

Abstract
Phosphatidylinositol 3-kinases (PI3K) are divided into three classes, which differ in their substrates and products. Class I generates the inositol phospholipids PI(3)P, PI(3,4)P2, and PI(3,4,5)P3 referred as PIP, PIP2, and PIP3, respectively. Class II produces PIP and PIP2, and class III generates only PIP. Substrate and product differences of the three classes are determined by the activation loops of their catalytic domains. Substitution of the class I activation loop with either class II or III activation loop results in a corresponding change of substrate preference and product restriction. We have evaluated such activation loop substitutions to show that oncogenic activity of class I PI3K is linked to the ability to produce PIP3. We further show that reduction of cellular PIP3 levels by the 5′-phosphatase PIPP interferes with PI3K-induced oncogenic transformation. PIPP also attenuates signaling through Akt and target of rapamycin. Class III PI3K fails to induce oncogenic transformation. Likewise, a constitutively membrane-bound class I PI3K mutant retaining only the protein kinase is unable to induce transformation. We conclude that PIP3 is an essential component of PI3K-mediated oncogenesis and that inability to generate PIP3 abolishes oncogenic potential. (Mol Cancer Res 2009;7(7):1132–8)
Data from Epidermal Growth Factor Receptor–Mediated Membrane Type 1 Matrix Metalloproteinase Endocytosis Regulates the Transition between Invasive versus Expansive Growth of Ovarian Carcinoma Cells in Three-Dimensional Collagen
Authors: Moss Natalie M. , Liu Yueying , Johnson Jeff J. , Debiase Philip , Jones Jonathan , Hudson Laurie G. , Munshi Hidayatullah G. , Stack M. Sharon
Published: January 2024

Abstract
The epidermal growth factor receptor (EGFR) is overexpressed in ovarian carcinomas and promotes cellular responses that contribute to ovarian cancer pathobiology. In addition to modulation of mitogenic and motogenic behavior, emerging data identify EGFR activation as a novel mechanism for rapid modification of the cell surface proteome. The transmembrane collagenase membrane type 1 matrix metalloproteinase (MT1-MMP, MMP-14) is a major contributor to pericelluar proteolysis in the ovarian carcinoma microenvironment and is subjected to extensive posttranslational regulation. In the present study, the contribution of EGFR activation to control of MT1-MMP cell surface dynamics was investigated. Unstimulated ovarian cancer cells display caveolar colocalization of EGFR and MT1-MMP, whereas EGFR activation prompts internalization via distinct endocytic pathways. EGF treatment results in phosphorylation of the MT1-MMP cytoplasmic tail, and cells expressing a tyrosine mutated form of MT1-MMP (MT1-MMP-Y573F) exhibit defective MT1-MMP internalization. As a result of sustained cell surface MT1-MMP activity, a phenotypic epithelial-mesenchymal transition is observed, characterized by enhanced migration and collagen invasion, whereas growth within three-dimensional collagen gels is inhibited. These data support an EGFR-dependent mechanism for regulation of the transition between invasive and expansive growth of ovarian carcinoma cells via modulation of MT1-MMP cell surface dynamics. (Mol Cancer Res 2009;7(6):809–20)
Data from Smad3 Is a Key Nonredundant Mediator of Transforming Growth Factor β Signaling in Nme Mouse Mammary Epithelial Cells
Authors: Dzwonek Joanna , Preobrazhenska Olena , Cazzola Silvia , Conidi Andrea , Schellens Ann , van Dinther Maarten , Stubbs Andrew , Klippel Anke , Huylebroeck Danny , ten Dijke Peter , Verschueren Kristin
Published: January 2024

Abstract
Smad2 and Smad3 are intracellular mediators of transforming growth factor β (TGFβ) signaling that share various biochemical properties, but data emerging from functional analyses in several cell types indicate that these two Smad proteins may convey distinct cellular responses. Therefore, we have investigated the individual roles of Smad2 and Smad3 in mediating the cytostatic and proapoptotic effects of TGFβ as well as their function in epithelial-to-mesenchymal transition. For this purpose, we transiently depleted mouse mammary epithelial cells (Nme) of Smad2 and/or Smad3 mainly by a strategy relying on RNaseH-induced degradation of mRNA. The effect of such depletion on hallmark events of TGFβ-driven epithelial-to-mesenchymal transition was analyzed, including dissolution of epithelial junctions, formation of stress fibers and focal adhesions, activation of metalloproteinases, and transcriptional regulation of acknowledged target genes. Furthermore, we investigated the effect of Smad2 and Smad3 knockdown on the TGFβ-regulated transcriptome by microarray analysis. Our results identify Smad3 as a key factor to trigger TGFβ-regulated events and ascribe tumor suppressor as well as oncogenic activities to this protein. (Mol Cancer Res 2009;7(8):1342–53)
Data from Prevalence and Functional Analysis of Sequence Variants in the ATR Checkpoint Mediator Claspin
Authors: Zhang Jianmin , Song Young-Han , Brannigan Brian W. , Wahrer Doke C.R. , Schiripo Taryn A. , Harris Patricia L. , Haserlat Sara M. , Ulkus Lindsey E. , Shannon Kristen M. , Garber Judy E. , Freedman Matthew L. , Henderson Brian E. , Zou Lee , Sgroi Dennis C. , Haber Daniel A. , Bell Daphne W.
Published: January 2024

Abstract
Mutational inactivation of genes controlling the DNA-damage response contributes to cancer susceptibility within families and within the general population as well as to sporadic tumorigenesis. Claspin (CLSPN) encodes a recently recognized mediator protein essential for the ATR and CHK1-dependent checkpoint elicited by replicative stress or the presence of ssDNA. Here, we describe a study to determine whether mutational disruption of CLSPN contributes to cancer susceptibility and sporadic tumorigenesis. We resequenced CLSPN from the germline of selected cancer families with a history of breast cancer (n = 25) or a multicancer phenotype (n = 46) as well as from a panel of sporadic cancer cell lines (n = 52) derived from a variety of tumor types. Eight nonsynonymous variants, including a recurrent mutation, were identified from the germline of two cancer-prone individuals and five cancer cell lines of breast, ovarian, and hematopoietic origin. None of the variants was present within population controls. In contrast, mutations were rare within genes encoding the CLSPN-interacting protein ATR and its binding partner ATRIP. One variant of CLSPN, encoding the I783S missense mutation, was defective in its ability to mediate CHK1 phosphorylation following DNA damage and was unable to rescue sensitivity to replicative stress in CLSPN-depleted cells. Taken together, these observations raise the possibility that CLSPN may encode a component of the DNA-damage response pathway that is targeted by mutations in human cancers, suggesting the need for larger population-based studies to investigate whether CLSPN variants contribute to cancer susceptibility. (Mol Cancer Res 2009;7(9):1510–16)
Data from COMP-Ang1 Potentiates the Antitumor Activity of 5-Fluorouracil by Improving Tissue Perfusion in Murine Lewis Lung Carcinoma
Authors: Hwang Jeong-Ah , Lee Eun Hui , Kim Hyun-Woo , Park Jin Bong , Jeon Byeong Hwa , Cho Chung-Hyun
Published: January 2024

Abstract
Chemotherapy is often hindered by abnormal tumor vascularity, which causes impaired delivery of drugs into the tumor. Angiopoietin-1 has potent roles in angiogenesis and vessel maturation. We report here that an angiopoietin-1 variant, COMP-Ang1, promotes vascular remodeling and pericyte coverage and thereby promotes the efficient delivery of a chemotherapeutic drug into tumors of murine Lewis lung carcinoma. The combination of COMP-Ang1 with the cytotoxic drug 5-fluorouracil potentiated the effect of 5-fluorouracil on tumor growth without increasing animal toxicity. Moreover, COMP-Ang1 increased perfusion into the tumor. Although COMP-Ang1 increased the functional vasculature in the tumor, COMP-Ang1 alone did not promote tumor growth, possibly due to its promotion of increased pericyte coverage. This study suggests that COMP-Ang1 may improve the microcirculation within a tumor by increasing functional vasculature and tissue perfusion and that the combination of chemotherapy together with COMP-Ang1 might be an advantageous therapeutic approach. (Mol Cancer Res 2009;7(12):1920–7)
Data from A Novel DNMT3B Splice Variant Expressed in Tumor and Pluripotent Cells Modulates Genomic DNA Methylation Patterns and Displays Altered DNA Binding
Authors: Gopalakrishnan Suhasni , Van Emburgh Beth O. , Shan Jixiu , Su Zhen , Fields C. Robert , Vieweg Johannes , Hamazaki Takashi , Schwartz Philip H. , Terada Naohiro , Robertson Keith D.
Published: January 2024

Abstract
DNA methylation is an epigenetic mark essential for mammalian development, genomic stability, and imprinting. DNA methylation patterns are established and maintained by three DNA methyltransferases: DNMT1, DNMT3A, and DNMT3B. Interestingly, all three DNMTs make use of alternative splicing. DNMT3B has nearly 40 known splice variants expressed in a tissue- and disease-specific manner, but very little is known about the role of these splice variants in modulating DNMT3B function. We describe here the identification and characterization of a novel alternatively spliced form of DNMT3B lacking exon 5 within the NH2-terminal regulatory domain. This variant, which we term DNMT3B3Δ5 because it is closely related in structure to the ubiquitously expressed DNMT3B3 isoform, is highly expressed in pluripotent cells and brain tissue, is downregulated during differentiation, and is conserved in the mouse. Creation of pluripotent iPS cells from fibroblasts results in marked induction of DNMT3B3Δ5. DNMT3B3Δ5 expression is also altered in human disease, with tumor cell lines displaying elevated or reduced expression depending on their tissue of origin. We then compared the DNA binding and subcellular localization of DNMT3B3Δ5 versus DNMT3B3, revealing that DNMT3B3Δ5 possessed significantly enhanced DNA binding affinity and displayed an altered nuclear distribution. Finally, ectopic overexpression of DNMT3B3Δ5 resulted in repetitive element hypomethylation and enhanced cell growth in a colony formation assay. Taken together, these results show that DNMT3B3Δ5 may play an important role in stem cell maintenance or differentiation and suggest that sequences encoded by exon 5 influence the functional properties of DNMT3B. (Mol Cancer Res 2009;7(10):1622–34)
Neutralizing Antibodies Impair the Oncolytic Efficacy of Reovirus but Permit Effective Combination with T cell–Based Immunotherapies
Authors: Groeneveldt Christianne , Kinderman Priscilla , Griffioen Lisa , Rensing Olivia , Labrie Camilla , van den Wollenberg Diana J.M. , Hoeben Rob C. , Coffey Matt , Loghmani Houra , Verdegaal Els M.E. , Welters Marij J.P. , van der Burg Sjoerd H. , van Hall Thorbald , van Montfoort Nadine
Published: January 2024

Reovirus type 3 Dearing (Reo), manufactured for clinical application as pelareorep, is an attractive anticancer agent under evaluation in multiple phase 2 clinical trials for the treatment of solid tumors. It elicits its anticancer efficacy by inducing both oncolysis and intratumoral T-cell influx. Because most people have been preexposed to Reo, neutralizing antibodies (NAb) are prevalent in patients with cancer and might present a barrier to effective Reo therapy. Here, we tested serum of patients with cancer and healthy controls (n = 100) and confirmed that Reo NAbs are present in >80% of individuals. To investigate the effect of NAbs on both the oncolytic and the immunostimulatory efficacy of Reo, we established an experimental mouse model with Reo preexposure. The presence of preexposure-induced NAbs reduced Reo tumor infection and prevented Reo-mediated control of tumor growth after intratumoral Reo administration. In B cell–deficient mice, the lack of NAbs provided enhanced tumor growth control after Reo monotherapy, indicating that NAbs limit the oncolytic capacity of Reo. In immunocompetent mice, intratumoral T-cell influx was not affected by the presence of preexposure-induced NAbs and consequently, combinatorial immunotherapy strategies comprising Reo and T-cell engagers or checkpoint inhibitors remained effective in these settings, also after a clinically applied regimen of multiple intravenous pelareorep administrations. Altogether, our data indicate that NAbs hamper the oncolytic efficacy of Reo, but not its immunotherapeutic capacity. Given the high prevalence of seropositivity for Reo in patients with cancer, our data strongly advocate for the application of Reo as part of T cell–based immunotherapeutic strategies.
A Case of HeartMate 3 Outflow Graft Twisting with Extraluminal Thrombosis: Is Computed Tomography Angiography Helpful?
Authors: Saleb Karim , Zagurovskaya Marianna , Sekela Michael , Guglin Maya
Published: January 2024

Twists in the outflow graft of the HeartMateTM 3 device (Abbott) have recently been described as a sporadic, late complication. We present a case with a unique combination of external compression of the HeartMate 3 outflow graft by a surgical scar compounded by thrombus formation in the space between the band relief and the outflow graft with associated twist of the outflow graft and severe flow limitation. Computed tomography angiogram (CTA) of the chest was suggestive of outflow graft thrombosis. Our case sheds additional light on the limited specificity of gated CTA in distinguishing the outflow graft twisting from thrombotic obstruction and kinking.
Heart Rate Variability: A possible machine learning biomarker for mechanical circulatory device complications and heart recovery
Authors: Lin Theodore , Khalpey Zain , Aras Shravan
Published: January 2024

Cardiovascular disease continues to be the number one cause of death in the United States, with heart failure patients expected to increase to >8 million by 2030. Mechanical circulatory support (MCS) devices are now better able to manage acute and chronic heart failure refractory to medical therapy, both as bridge to transplant or as bridge to destination. Despite significant advances in MCS device design and surgical implantation technique, it remains difficult to predict response to device therapy. Heart rate variability (HRV), measuring the variation in time interval between adjacent heartbeats, is an objective device diagnostic regularly recorded by various MCS devices that has been shown to have significant prognostic value for both sudden cardiac death as well as allcause mortality in congestive heart failure (CHF) patients. Limited studies have examined HRV indices as promising risk factors and predictors of complication and recovery from left ventricular assist device therapy in end-stage CHF patients. If paired with new advances in machine learning utilization in medicine, HRV represents a potential dynamic biomarker for monitoring and predicting patient status as more patients enter the mechanotrope era of MCS devices for destination therapy.
Occupational Therapy’s Role with Ventricular Assist Devices and the Promotion of Travel Protocols
Authors: Chandra Natasha , Suplick Linda
Published: January 2024

An option for individuals diagnosed with end-stage heart failure is to receive a ventricular assist device (VAD). In 2006, Shepherd and Wilding produced an article regarding occupational therapy’s role during the VAD process as they anticipated a growing need for this area of practice. Since that time, there continues to be a lack of supporting literature on occupational therapy’s important role with this population. Therefore, the purpose of this article is to explain an occupational therapist’s contribution on the VAD team, offer opportunities and interventions for enhancing quality of life for this unique population, and discuss an innovative travel protocol implemented at Morristown Medical Center.
What is a VAD Social Worker? A National Perspective
Authors: Combs Pamela , Cohen William , Siddiqi Umar , Jeevanandam Valluvan
Published: January 2024

Ventricular Assist Device Social Workers (VAD SWs) are mandated members of VAD care teams and contribute to the psychosocial aspect of patient care within the United States. However, the contributions and methods of the VAD SW are relatively undefined. This article reports the results of two national surveys regarding VAD SWs. One survey ascertains the VAD SW’s views of their work and their role in the VAD care team. The other survey assesses the VAD SWs involvement with care, through the perspective of the VAD team. Our results indicate that SWs are not only routinely involved in VAD patient selection but during the whole health care continuum. VAD SWs are well integrated within the VAD care team, and they are influential in the evaluation process. Agreement exists between VAD care teams and the national guidelines regarding the importance of psychosocial care provided by a VAD SW; however, no standardized protocol exists for pre-implant evaluations, screening for substance abuse, or assessing caregiver support.
Angiotensin Inhibition and Gastrointestinal Bleeding Prevention in Patients with Left Ventricular Assist Devices
Authors: Weeks Phillip
Published: January 2024

Gastrointestinal bleeding remains a common complication in advanced heart failure patients following implantation of continuous-flow left ventricular assist devices. While the cause is likely multifactorial, development of arterial venous malformations in the gastrointestinal mucosa are a key factor. Inhibition of angiotensin II activity has been postulated to disrupt the signaling that promotes angiogenesis in these patients. We aim to review the theoretical basis for angiotensin receptor blockade, which has been proposed and explore the published evidence regarding this therapy and gastrointestinal bleeding in LVAD patients.
Transcutaneous Energy Transmission: Can we do it now?
Authors: Pya Yuriy
Published: January 2024

The percutaneous driveline used in contemporary LVADs presents a continuous risk of infection for the duration of support. Minimizing infection in durable mechanical circulatory support systems requires total implantation of all components and energy transfer by means other than percutaneous drivelines. A novel coplanar energy transfer (CET) system, similar to the original transcutaneous energy transfer (TET) design, is unique by incorporating two large rings with coil-within-the-coil topology to ensure strong resonance power. The CET system consists of an internal integrated controller, a battery coupled with an internal thoracic coil ring, and the LVAD pump. External equipment includes a power transmission belt with an external controller, a battery, and wristwatch monitor. The CET system is adaptable to multiple LVAD designs, though the Jarvik 2000 (Jarvik Heart, Inc., New York, NY) with postauricular power cable was used in the initial clinical cases. Two male patients, ages 51 years and 24 years, underwent implantation of the CET/Jarvik 2000 system for the bridge to transplant indication. One patient experienced a stroke and device thrombosis which led to termination of LVAD support while the patient waited for transplantation. The second patient underwent successful transplant after two months of support. The CET functioned as intended in both patients. Larger, multicenter, controlled clinical trials are necessary to determine the long-term safety and efficacy of the CET technology.
Successful pregnancy with centrifugal flow left ventricular assist device: A case report and review of the literature
Authors: Dehkordi Seyed , Lippmann Matthew , Abicht Travis , Sauer Andrew , Haglund Nicholas , Parrish Marc , Staab Jared , Gupta Bhanu
Published: January 2024

Successful deliveries from patients supported by axial flow left ventricular devices have been previously reported. We present the first case of a successful pregnancy and birth in a patient with a centrifugal-flow left ventricular assist device. A 24-year-old female with methamphetamine-induced cardiomyopathy and end-stage congestive heart failure supported by a HeartWare™ ventricular assist device (Medtronic) presented two years after device implantation with an unplanned pregnancy at 11-weeks of gestation. Following a multidisciplinary evaluation by experts in advanced heart failure, maternal fetal medicine, cardiothoracic surgery, anesthesia, ethics, psychiatry, and palliative care, an advanced plan of care was established. An elective induction of labor was scheduled for the 34th week of gestation. Given poor labor progression despite maximal induction efforts, the patient was transferred to a cardiothoracic operating room where she delivered a healthy baby boy via Cesarean section under close hemodynamic monitoring by advanced heart failure and cardiothoracic surgery teams.
Guideline-Directed Heart Failure Therapy in Patients after Left Ventricular Assist Device Implantation
Authors: Colvin Bailey , Coons James , Beavers Craig
Published: January 2024

Background: Left ventricular assist devices (LVADs) are used as an advanced therapy option for patients with stage D heart failure. These devices provide mechanical unloading of the heart as either a bridge to transplant or recovery, or as destination therapy. In patients with LVADs, there are emerging data on the use of heart failure guideline-directed medical therapy (GDMT) to improve outcomes. This review describes the current evidence available for the use of neurohormonal blocking agents in patients with LVADs. Methods: Articles were found using PubMed and web searches for heart failure therapies/neurohormonal blockade and LVADs. Studies were included if they evaluated the use of the heart failure therapies, either retrospectively or prospectively. Results: A total of 17 articles and 9 abstracts were reviewed. The totality of data surrounding the use of GDMT neurohormonal blockade in patients with LVADs are limited in nature. Much of the data are limited either by use of surrogate outcomes, single center evaluations, and/or small sample sizes. However, the evidence does support clinical benefit with associated mechanistic plausibility. More research is needed to understand appropriate patient selection and means to optimize these therapies in the LVAD population. Conclusion: Combined neurohormonal blockade appears to reduce morbidity and mortality in patients with LVAD implants.
Removal of Impella in the Setting of Left Ventricular Thrombus: A Potential Indication for Cerebral Embolic Protection Devices
Authors: Asadourian Miro , Sharma Avinash , Kiel Richard , Lin Felice , Bhullar Manminder
Published: January 2024

Successful percutaneous mechanical circulatory support (MCS) has been used for acute stabilization of cardiogenic shock (CS). Improved survival outcomes have been observed in patients with CS from an acute myocardial infarction (AMI) who undergo implantation of left ventricular (LV) to ascending aorta rotodynamic pumps, such as the Impella® device (Abiomed). However, thrombotic events are a known complication of such devices in poor flow states such as CS. There is limited evidence regarding the management of patients who develop an LV thrombus after Impella insertion. Currently, the Sentinel cerebral protection system (SCPS, Boston Scientific) is the only FDA-approved device for cerebral embolic protection during transcatheter aortic valve replacement procedures. While the use of a cerebral embolic protection device (CEPD) has a theoretical benefit, no current CEPD is approved for use in conjunction with Impella device removal or other MCS devices. We present a case describing the use of the SCPS during the removal of the Impella CP device in a patient who developed an LV thrombus after CS from AMI. Our case highlights a potential role for the expanded use of CEPDs in similar clinical scenarios.
Feasibility of the use of a Stereoscopic Camera In the Final Inclusion (SCI-FI) of Donor Organ Assessment Using Virtual Reality Technology
Authors: Salas de Armas Ismael , Marcano Juan , Patel Jayeshkumar , Akay M. , Patel Manish , Akkant Bindu , Jumean Marwan , Kumar Sachin , Radovancevic Rajko , Nathan Sriram , Kar Biswajit , Gregoric Igor
Published: January 2024

Objective: Donor organ assessment is challenging, particularly when physicians and surgeons have to make decisions remotely. To improve communication and preparation for the transplant process, we proposed that a versatile, secure, and transportable video presence would enable a detailed assessment of donor organs. Methods: A virtual reality camera with a 360-degree visualization range was used with a smartphone receiver to enable integral assessment of the donor's heart in the operating room, with visualization of the organs in real time. Prospective, observational data was collected in two cases in this proof-of-concept study. An assessment physician evaluated the donor heart remotely, and the assessment physician’s conclusions were compared to the transplanting surgeon. Results: The assessment physician was able to adjust the view, angle, contrast, and zoom of the images independently and deemed the organs suitable for transplant, which correlated in a blinded fashion with the procurement surgeon’s independent assessment. Discussion: Usage of 360-degree high definition cameras and real-time, three-dimensional mobile receivers may be a feasible approach to apply to organ procurement, allowing physicians located remotely from the procurement center to participate and assist in the final intraoperative assessment for organ acceptance.
What Did We Learn about VADs in 2021?
Authors: Guglin Maya
Published: January 2024

This is our 8th annual literature review on mechanical circulatory support (MCS) devices. Our previous reports were well received by the readers. The full text of the reviews for 2014, 2015, 2016, 2017, 2018, 2019, and 20201-7 were downloaded 821, 861, 701, 869, 951, 272, and 365 times, respectively. In this review, we summarized the most interesting and important, from our standpoint, publications from 2021. There may be some slight overlap with the end of 2020 because some papers were published online first, and the year of the publication changed when they became available in print. For the fifth time, we added a section on extracorporeal membrane oxygenation (ECMO), which primarily addresses new developments in veno-arterial ECMO. Readers who wish to supplement this review, argue with the author’s statements, or express their opinions are encouraged to do so by sending letters to the editor at mguglin@iu.edu or posting on our Facebook page at https://www.facebook.com/TheVADJournal.
Acute Pump Thrombosis within One Hour of a HeartMate 3 Implantation: Case Report
Authors: Shah Zubair , Acosta Noel , Goyal Amandeep , Dalia Tarun , Henkel Sarah , Abicht Travis
Published: January 2024

A 39-year-old male with a history of non-ischemic cardiomyopathy underwent a HeartMate 3 (Abbott Laboratories) implantation. Within an hour of implantation, low flow alarms were noted before exiting the operating room. The alarm was secondary to acute pump thrombosis. This is the first reported case of thrombosis immediately post-implant.
Pulsatility is a Predictive Marker of Improved Cardiac Function in Patients with Liquid Matrix-treated Left Ventricular Assist Devices
Authors: Mikail Philemon , Skaria Rinku , Slepian Marvin , Garcia Janny , Smith Richard , Khalpey Zain
Published: January 2024

Objective: Left ventricular assist devices (LVADs) are utilized as a bridge to transplant or as destination therapy for patients with end-stage heart failure. Although cardiac offloading from these devices rarely leads to complete remodeling and functional recovery, the use of mesenchymal cells to modulate heart failure has been explored in recent years due to its intrinsic regenerative properties. Current methods of evaluating cardiac function have too much variability, difficulty of access, or require too frequent follow up to create universal weaning protocols. We hypothesized that the administration of amniotic allograft liquid matrix (LM) containing amnion-derived mesenchymal stem cells (aMSCs) in patients with LVADs could improve left ventricular function and be positively associated with pulsatility. Methods: Flow cytometry, mass spectroscopy, and enzyme-linked immunoassays were used to characterize aMSCs and LM that were administered to 9 patients with LVADs. Results were compared to samples from 7 control patients with LVADs that did not receive aMSC and LM. Results: Patients who received aMSCs and LM (n=9) demonstrated a significant increase in standardized pulsatility at 30 (P = .007), 90 (P = .02), and 180 (P = .05) days post-implant when compared to control patients who did not receive the treatment (n=7). Discussion: We conclude that the use of aMSCs and LM in patients with LVADs could be a promising treatment strategy, and pulsatility can be a reproducible and consistent diagnostic metric to evaluate left ventricular function without intra- or inter-observer variability.
Intra-aortic Balloon Pump May Attenuate Adverse Hemodynamic Effects of Negative Intrathoracic Pressure in Cardiogenic Shock
Authors: Araj Faris
Published: January 2024

High negative intrathoracic pressure (NIP), as occurs during obstructive sleep apnea or hiccups, results in adverse hemodynamic consequences, specifically a decrease in left ventricle (LV) performance. These untoward effects can potentially be catastrophic in the case of an already compromised LV in cardiogenic shock. The interplay of intra-aortic balloon pump counter pulsation during abrupt high NIP in cardiogenic shock is described.
Successful Percutaneous Management of LVAD Outflow Graft Stenosis: Role of Invasive Hemodynamics in Decision Making
Authors: Dalia Tarun , Goyal Amandeep , Mehta Harsh , Foster Henedine , Hockstad Eric , Rohr Aaron , Johnson Philip , Abicht Travis , Gupta Bhanu
Published: January 2024

Left ventricular assist device (LVAD) outflow graft stenosis (OGS) is a rare but lethal complication. We present a case of a 79-year-old male with pertinent past medical history of an LVAD implanted as destination therapy, stage III chronic kidney disease, and hypertension. He was admitted for low-flow alarms, and the echocardiogram showed stable right ventricle function and no pericardial effusion. Invasive hemodynamic assessments demonstrated a peak-to-peak gradient of 90 mm Hg in the outflow graft between the mid and distal ends of the graft on pullback. Contrast angiography confirmed OGS. The OGS was successfully treated with a VBX-covered stent (Gore). OGS should be considered when low flow alarms are found in patients with LVADs.
X-Linked Lymphoproliferative Syndrome: A Spectrum of Clinical and Immunological Profile and Novel Pathogenic Variants from Chandigarh, India
Authors: Jindal Ankur Kumar , Mondal Sanjib , Sil Archan , Rawat Amit , Chawla Sanchi , Tyagi Rahul , Sudhakar Murugan , Banday Aaqib Zaffar , Suri Deepti , Vignesh Pandiarajan , Dhaliwal Manpreet , Sharma Saniya , Rikhi Rashmi , Saka Ruchi , Sharma Rajni , Chatterjee Debajyoti , Sreedharanunni Sreejesh , Uppuluri Ramya , Raj Revathi , Singh Surjit
Published: January 2024

Introduction: X-linked lymphoproliferative syndrome (XLP) is a rare primary immune deficiency. Two types of XLP have been described: XLP-1 and XLP-2. Methods: We found 7 patients with XLP (3 had XLP-1 and 4 had XLP-2) after reviewing the data from Pediatric Immunodeficiency Clinic from 1997 to 2021. Results: Mean age at diagnosis was 3.8 years, and mean delay in diagnosis was 2.6 years. Five patients had recurrent episodes of infections. Four patients developed at least one episode of hemophagocytic lymphohistiocytosis (HLH) (2 with XLP-1 and 2 with XLP-2). Of these, 2 had recurrent HLH (both with XLP-2). Epstein-Barr virus (EBV) infection was detected in 2 (1 with XLP-1 and 1 with XLP-2). Both these patients had HLH. One child with XLP-2 had inflammatory bowel disease. Hypogammaglobulinemia was seen in 3 (2 with XLP-1 and 1 with XLP-2). Genetic analysis showed previously reported variants in 5, while 2 had novel variants (one in exon 7 of XIAP gene [c.1370dup p.Asn457Lysfs Ter16] and other had splice site variant in intron 1 of SH2D1A gene [c.138-2_138-1insG]). Episodes of HLH were managed with intravenous immunoglobulin (IVIg), methylprednisolone, oral prednisolone, cyclosporine, and rituximab. Inflammatory bowel disease was managed using oral prednisolone and azathioprine. One patient underwent haploidentical hematopoietic stem cell transplantation. One child with XLP-2 and WAS died because of fulminant pneumonia. Discussion/Conclusions: XLP should be considered as a strong possibility in any patient with features of HLH, repeated infections with hypogammaglobulinemia, persistent EBV infection, and early-onset IBD.
Point Cloud Registration for Measuring Shape Dependence of Soft Tissue Deformation by Digital Twins in Head and Neck Surgery
Authors: Monji-Azad Sara , Männle David , Hesser Jürgen , Pohlmann Jan , Rotter Nicole , Affolter Annette , Weis Cleo Aron , Ludwig Sonja , Scherl Claudia
Published: January 2024

Introduction: A 2½ D point cloud registration method was developed to generate digital twins of different tissue shapes and resection cavities by applying a machine learning (ML) approach. This demonstrates the feasibility of quantifying soft tissue shifts. Methods: An ML model was trained using simulated surface scan data obtained from tumor resections in a pig head cadaver model. It hereby uses 438 2½ D scans of the tissue surface. Tissue shift was induced by a temperature change from 7.91 ± 4.1°C to 36.37 ± 1.28°C. Results: Digital twins were generated from various branched and compact resection cavities (RCs) and cut tissues (CT). A temperature increase induced a tissue shift with a significant volume increase of 6 mL and 2 mL in branched and compact RCs, respectively (p = 0.0443; 0.0157). The volumes of branched and compact CT were decreased by 3 and 4 mL (p < 0.001). In the warm state, RC and CT no longer fit together because of the significant tissue deformation. Although not significant, the compact RC showed a greater tissue deformation of 1 μL than the branched RC with 0.5 μL induced by the temperature change (p = 0.7874). The branched and compact CT forms responded almost equally to changes in temperature (p = 0.1461). Conclusions: The simulation experiment of induced soft tissue deformation using digital twins based on 2½ D point cloud models proved that our method helps to quantify shape-dependent tissue shifts.
Early Feeding for the Prevention of Neonatal Hypoglycaemia: A Systematic Review and Meta-Analysis
Authors: Roberts Lily F. , Harding Jane E. , Crowther Caroline A. , Watson Estelle , Wang Zeke , Lin Luling
Published: January 2024

Background: Poor feeding, among other factors, predisposes neonates to hypoglycaemia. Early feeding is widely recommended to prevent hypoglycaemia in those at risk, but the effectiveness of this is uncertain. This review aimed to summarise and analyse the evidence on the effectiveness of early feeding for prevention of neonatal hypoglycaemia. Methods: Four databases and three clinical trial registries were searched from inception to May 24, 2023. Published and unpublished randomised controlled trials (RCTs), quasi-RCTs, cluster randomised trials, non-randomised studies of interventions, and observational studies with comparison groups were considered for inclusion with no language or publication date restrictions. We included studies of neonates who were fed early (within 60 min of birth or study defined) versus delayed. Study quality was assessed using the Cochrane Risk of Bias 1 tool or Effective Public Health Practice Project Quality Assessment tool. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RevMan 5.4.1 or R was used to synthesise results in random-effects meta-analyses. This review was registered prospectively with PROSPERO (CRD42022378904). Results: A total of 175,392 participants were included across 19 studies, of which two were RCTs, 14 cohort studies, two cross-sectional studies, and one a case-control study. Most studies (13/19) were conducted in low- or lower-middle-income countries. Early feeding may be associated with reduced neonatal hypoglycaemia (four cohort studies, 744 infants, odds ratio [OR] 0.19 (95% CI: 0.10–0.35), p < 0.00001, I2 = 44%) and slightly reduced duration of initial hospital stay (one cohort study, 1,673 infants, mean difference: –0.20 days [95% CI: −0.31 to −0.09], p = 0.0003), but the evidence is very uncertain. One RCT found early feeding had little or no effect on the risk of neonatal mortality, but three cohort studies found early feeding may be associated with reduced risk (136,468 infants, OR 0.51 [95% CI: 0.37–0.72]; low certainty evidence; p <0.0001; I2 = 54%). Conclusion: We found that early feeding may reduce the incidence of neonatal hypoglycaemia, but the evidence is very uncertain. Given its many other benefits, early feeding should continue to be recommended. This review was primarily funded by the Aotearoa Foundation and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health.
Higher Depressive Symptoms in Irregular Menstrual Cycles: Converging Evidence from Cross-Sectional and Prospective Assessments
Authors: Klusmann Hannah , Kapp Claudia , Engel Sinha , Schumacher Tabea , Bücklein Elise , Knaevelsrud Christine , Schumacher Sarah
Published: January 2024

Background: Menstrual cycle regularity is an important marker of reproductive health and associated with physiological and psychological illnesses, as well as experiencing stress. We hypothesized that individuals with irregular menstrual cycles report higher depressive symptom severity, after controlling for stress occurrence. Methods: The hypothesis was examined through two measurement approaches: a cross-sectional and a prospective, longitudinal study. In the cross-sectional study, participants (n = 394) reported depressive symptoms and their overall menstrual cycle regularity. In the longitudinal study, participants (n = 77) completed questionnaires on depressive symptoms and stress during the mid-follicular and periovulatory phase of one menstrual cycle. Depressive symptoms were compared between participants with regular and irregular cycles through a Welch t test and an ANCOVA. Results: Participants with irregular menstrual cycles reported more depressive symptoms in the cross-sectional analysis. Similarly, in the longitudinal analysis, the group with a current irregular menstrual cycle reported more depressive symptoms after controlling for stress occurrence. When including only complete data sets without multiple imputation (n = 52), the direction of the effects remained but did not reach statistical significance. Conclusions: The results indicate an association between depressive symptoms and menstrual cycle irregularity. Limitations were that although we investigated the menstrual cycle prospectively, it would have been more precise to include two or more cycles and daily sex hormone measurements. Further limitations were the suboptimal statistical power and the data collection during the COVID pandemic. We give recommendations on how to incorporate the association of depressive symptoms and cycle irregularity in future study designs on women’s mental health.
Dermoscopic Features of Heterotopic Salivary Gland Tissue in the Neck: Report of a Case
Authors: Inoue Shinichiro , Maeda Takuya , Nagata Yuri , Yanagi Teruki , Ujiie Hideyuki
Published: January 2024

Introduction: Heterotopic salivary gland tissue (HSGT) is diagnosed when salivary gland tissue is found in areas other than the major or minor salivary glands. No dermoscopic findings of HSGT have been reported. Case Presentation: This case report gives the dermoscopic findings of a 45-year-old woman with HSGT who presented with a longstanding pale red macule on her neck, characterized by repeated clear fluid discharge. Dermoscopic examination showed a red dot with a pale pink halo and telangiectasia throughout the lesion. An excisional biopsy confirmed the diagnosis of HSGT, revealing the presence of mucous and serous salivary glandular structures within subcutaneous fat tissue. It has been reported that HSGT is associated with periductal lymphocytic infiltration, which was also observed in this case. Conclusion: We think that the “red dot with a pale pink halo” is a unique dermoscopic finding of HSGT, which is rarely observed in branchial anomalies.
Discrepancy between Caregivers’ Reports and Physicians’ Evaluation of Causative Foods in Food Protein-Induced Enterocolitis Syndrome in Japan: The Japan Environment and Children’s Study
Authors: Kajita Naoki , Kaneko Makoto , Kuroki Makoto , Tomita Makoto , Kawakami Chihiro , Ito Shuichi ,   the Japan Environment and Children’s Study (JECS) Group
Published: January 2024

Introduction: Food protein-induced enterocolitis syndrome (FPIES) is a form of non-IgE-mediated gastrointestinal food allergy. FPIES is considered a rare food allergy disorder and is often under-recognized. Therefore, clinicians should have a better understanding of its manifestations and maintain a high index of suspicion for a correct diagnosis. To this end, information about differences in the characteristics of caregiver-reported and physician-diagnosed FPIES is important. Methods: The present, national, multicentric, prospective birth cohort study, called the Japan Environment and Children’s Study (JECS), enrolled a general population of 104,062 fetal records. The characteristics of FPIES in 1.5-year-old children were categorized as cases reported by caregivers or as those diagnosed by a physician using questionnaire data. Results: The prevalence of caregiver-reported and physician-diagnosed FPIES cases was 0.69% and 0.06%, respectively. Among the former, the most common causative food was hen’s egg (HE), and the second most common causative food was cow’s milk (CM) (51.0% and 17.1% of patients responded to HE and CM, which accounted for 46% and 15% of all the causative foods, respectively). Conversely, among the physician-diagnosed cases, the most common causative food was CM followed by HE (57.7% and 36.5% of patients responded to CM and HE, which accounted for 46% and 29% of all the causative foods, respectively). CM accounted for a significantly higher proportion of causative foods in physician-diagnosed FPIES while HE accounted for a significantly higher proportion of caregiver-reported FPIES (p < 0.05). Conclusion: A discrepancy was found in reports of the most common causative food between caregiver-reported and physician-diagnosed cases of FPIES.
Staghorn Caliceal Hem-o-lok Stone: A Long-Term Complication of Robotic Partial Nephrectomy – A Case Report and Literature Review
Authors: Dibitetto Francesco , Russo Pierluigi , Marino Filippo , Ragonese Mauro , Nigro Domenico , Foschi Nazario
Published: January 2024

Introduction: Hem-o-lok clips (HOLCs) are a useful tool in mini-invasive surgery, especially for renal surgery. However, in rare cases, they could migrate into the collecting system and be calculogenic. Case Presentation: We present a case of a 53 years old man with an incidental CT finding of a left staghorn caliceal stone increasing its size in the last 2 years. He had a medical history of ipsilateral robotic partial nephrectomy (RAPN) at another institution 8 years before and a previous renal colic with spontaneous stone elimination about 20 years before. The stone was located in the upper calyx. He underwent a flexible ureteroscopy. After an initial fragmentation, a Hem-o-lok was reported, partially wedged into the renal parenchyma. After removing the HOLC with a basket, a small urinary leak was observed and managed with a JJ stent placement. In the postoperative period, the patient had a fever managed with antibiotics and was discharged on the 4th postoperative day without problems. Conclusion: HOLC migration into the collecting system is a rare complication following robotic and laparoscopic renal surgery. HOLC could act as a nidus for stone formation. Avoiding too much tension during renal sutures using HOLC could reduce the possibility of migration. Simple knotting in particular conditions is a valuable option. However, this kind of stone can be managed endoscopically without complaints, minding the possibility that HOLC could be partially wedged into renal parenchyma leading to a urinary leak. With the widening indications for RAPN, this kind of complication could be more frequent.
Abnormal Shape and Size of the Cardiac Ventricles Are Associated with a Higher Risk of Neonatal Death in Fetuses with Isolated Left Congenital Diaphragmatic Hernia
Authors: Huntley Erin S. , Hernandez-Andrade Edgar , Papanna Ramesha , Bergh Eric , Espinoza Jimmy , Soto Eleazar , Lopez Suzanne M. , Harting Matthew T. , Johnson Anthony
Published: January 2024

Introduction: The objective of this study was to evaluate the association between fetal cardiac deformation analysis (CDA) and cardiac function with severe adverse perinatal outcomes in fetuses with isolated left congenital diaphragmatic hernia (CDH). Methods: CDA in each ventricle (contractility, size, and shape), evaluated by speckle tracking and novel FetalHQ software, and markers of cardiac function (E/A ratios, pulmonary and aortic peak systolic velocities, and sigmoid annular valve diameters), were evaluated in fetuses with isolated left CDH. Two evaluations were performed: at referral (CDA and function) and within 3 weeks of delivery (CDA). Severe adverse neonatal outcomes were considered neonatal death (ND) or survival with CDH-associated pulmonary hypertension (CDH-PH). Differences and associations between CDA, cardiac function, and severe adverse outcomes were estimated. Results: Fifty fetuses were included, and seventeen (34%) had severe adverse neonatal outcomes (11 ND and 6 survivors with CDH-PH). At first evaluation, the prevalence of a small left ventricle was 34% (17/50) with a higher prevalence among neonates presenting severe adverse outcomes (58.8 [10/17] vs. 21.2% [7/33]; p = 0.01; OR, 5.03 [1.4–19.1; p = 0.01]) and among those presenting with neonatal mortality (8/11 [72.7] vs. 9/39 [23.0%]; p = 0.03; OR, 8.9 [1.9–40.7; p = 0.005]). No differences in cardiac function or strain were noted between fetuses with or without severe adverse outcomes. Within 3 weeks of delivery, the prevalence of small left ventricle was higher (19/34; 55.8%) with a more globular shape (reduced transverse/longitudinal ratio). A globular right ventricle was significantly associated with ND or survival with CDH-PH (OR, 14.2 [1.5–138.3]; p = 0.02). Conclusion: Fetuses with isolated CDH at risk of perinatal death or survival with CDH-PH had a higher prevalence of a small left ventricle and abnormal shape of the right ventricle.