Showing papers by "University of Medicine and Dentistry of New Jersey published in 2018"

The Novel Roles of Connexin Channels and Tunneling Nanotubes in Cancer Pathogenesis

Abstract: Neoplastic growth and cellular differentiation are critical hallmarks of tumor development. It is well established that cell-to-cell communication between tumor cells and "normal" surrounding cells regulates tumor differentiation and proliferation, aggressiveness, and resistance to treatment. Nevertheless, the mechanisms that result in tumor growth and spread as well as the adaptation of healthy surrounding cells to the tumor environment are poorly understood. A major component of these communication systems is composed of connexin (Cx)-containing channels including gap junctions (GJs), tunneling nanotubes (TNTs), and hemichannels (HCs). There are hundreds of reports about the role of Cx-containing channels in the pathogenesis of cancer, and most of them demonstrate a downregulation of these proteins. Nonetheless, new data demonstrate that a localized communication via Cx-containing GJs, HCs, and TNTs plays a key role in tumor growth, differentiation, and resistance to therapies. Moreover, the type and downstream effects of signals communicated between the different populations of tumor cells are still unknown. However, new approaches such as artificial intelligence (AI) and machine learning (ML) could provide new insights into these signals communicated between connected cells. We propose that the identification and characterization of these new communication systems and their associated signaling could provide new targets to prevent or reduce the devastating consequences of cancer.

Robotic-assisted laparoscopic repair of ureteral injury: an evidence-based review of techniques and outcomes.

Abstract: Introduction Iatrogenic ureteral injuries represent a common surgical problem encountered by practicing urologists. With the rapidly expanding applications of robotic-assisted laparoscopic surgery, ureteral reconstruction has been an important field of recent advancement. This collaborative review sought to provide an evidence-based analysis of the latest surgical techniques and outcomes for robotic-assisted repair of ureteral injury. Evidence acquisition A systematic review of the literature up to December 2017 using PubMed/Medline was performed to identify relevant articles. Those studies included in the systematic review were selected according to Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria. Additionally, expert opinions were included from study authors in order to critique outcomes and elaborate on surgical techniques. A cumulative outcome analysis was conducted analyzing comparative studies on robotic versus open ureteral repair. Evidence synthesis Thirteen case series have demonstrated the feasibility, safety, and success of robotic ureteral reconstruction. The surgical planning, timing of intervention, and various robotic reconstructive techniques need to be tailored to the specific case, depending on the location and length of the injury. Fluorescence imaging can represent a useful tool in this setting. Recently, three studies have shown the feasibility and technical success of robotic buccal mucosa grafting for ureteral repair. Soon, additional novel and experimental robotic reconstructive approaches might become available. The cumulative analysis of the three available comparative studies on robotic versus open ureteral repair showed no difference in operative time or complication rate, with a decreased blood loss and hospital length of stay favoring the robotic approach. Conclusions Current evidence suggests that the robotic surgical platform facilitates complex ureteral reconstruction in a minimally invasive fashion. High success rates of ureteral repair using the robotic approach mirror those of open surgery, with the additional advantage of faster recovery. Novel techniques in development and surgical adjuncts show promise as the role of robotic surgery evolves.

Delirium Screening and Management in Inpatient Rehabilitation Facilities.

Abstract: Delirium is an acute and fluctuating disturbance in cognition attention and awareness that is often a reflection of abnormal physiological condition of an individual. Delirium is highly prevalent among an older population and is associated with high mortality, poor medical and functional outcomes, and high healthcare cost. Delirium often has iatrogenic triggers, and it has been recognized as a quality indicator of healthcare organizations. Despite its high prevalence and significance, more than 50% of the delirium cases are underrecognized by healthcare professionals and remained untreated. Most patients in inpatient rehabilitation facilities are older adults with multiple risk factors for delirium including operation, intensive care stay, multiple co-morbidities, and impaired mobility. Early detection, intervention, and primary prevention of delirium will allow patients to avoid additional morbidities and reach their maximum functional potential during their rehabilitation stay. After the systematic implementation of delirium screening in our inpatient rehabilitation facility, we found that 10.3% of patients were screened positive for delirium at admission. This review discusses the systematic implementation of screening and intervention for delirium as well as the epidemiology of delirium to increase the awareness and guide clinical practice for clinicians in inpatient rehabilitation facilities.

3D Bioprinting and Stem Cells.

Abstract: Three-dimensional (3D) in vitro modeling is increasingly relevant as two-dimensional (2D) cultures have been recognized with limits to recapitulate the complex endogenous conditions in the body Additionally, fabrication technology is more accessible than ever Bioprinting, in particular, is an additive manufacturing technique that expands the capabilities of in vitro studies by precisely depositing cells embedded within a 3D biomaterial scaffold that acts as temporary extracellular matrix (ECM) More importantly, bioprinting has vast potential for customization This allows users to manipulate parameters such as scaffold design, biomaterial selection, and cell types, to create specialized biomimetic 3D systemsThe development of a 3D system is important to recapitulate the bone marrow (BM) microenvironment since this particular organ cannot be mimicked with other methods such as organoids The 3D system can be used to study the interactions between native BM cells and metastatic breast cancer cells (BCCs) Although not perfect, such a system can recapitulate the BM microenvironment Mesenchymal stem cells (MSCs), a key population within the BM, are known to communicate with BCCs invading the BM and to aid in their transition into dormancy Dormant BCCs are cycling quiescent and resistant to chemotherapy, which allows them to survive in the BM to resurge even after decades These persisting BCCs have been identified as the stem cell subset These BCCs exhibit self-renewal and can be induced to differentiate More importantly, this BCC subset can initiate tumor formation, exert chemoresistance, and form gap junction with endogenous BM stroma, including MSCs The bioprinted model detailed in this chapter creates a MSC-BC stem cell coculture system to study intercellular interactions in a model that is more representative of the endogenous 3D microenvironment than conventional 2D cultures The method can reliably seed primary BM MSCs and BC stem cells within a bioprinted scaffold fabricated from CELLINK Bioink Since bioprinting is a highly customizable technique, parameters described in this method (ie, cell-cell ratio, scaffold dimensions) can easily be altered to serve other applications, including studies on hematopoietic regulation

New features for measuring disease activity in pediatric localized scleroderma

Abstract: Objective. To identify clinical features that define disease activity in pediatric localized scleroderma (LS), and determine their specificity and importance. Methods. We conducted a multicenter prospective study of patients with active and inactive LS skin lesions. A standardized evaluation of a single designated study lesion per subject was performed at 3 visits. We evaluated the pattern and correlation between assessed features and physician’s global assessments of activity (PGA-A). Results. Ninety of 103 subjects had evaluable data; 66 had active and 24 inactive disease. Subjects had similar age of onset, sex, and disease patterns. Linear scleroderma was the most common subtype. Features specific for active disease included erythema, violaceous color, tactile warmth, abnormal skin texture, and disease extension. Scores for these variables changed over time and correlated with PGA-A of the lesion. Active and inactive lesions could not be distinguished by the presence or level of skin thickening, either of lesion edge or center. However, in active lesions, skin thickening scores did correlate with PGA–A scores. Regression analysis identified the combination of erythema, disease extension, violaceous color, skin thickening, and abnormal texture as predictive of PGA-A at study entry. Damage features were common irrespective of activity status. Conclusion. We identified variables strongly associated with disease activity, expanding upon those used in current measures, and determined their relative importance in physician activity scoring. Skin thickening was found to lack specificity for disease activity. These results will help guide development of a sensitive, responsive activity tool to improve care of patients with LS.

Causes of Emergency Department Overcrowding and Blockage of Access to Critical Services in Beijing: A 2-Year Study

Abstract: Background Emergency department (ED) overcrowding is a serious issue worldwide. Objectives This study was done to evaluate the degree of overcrowding in local “teaching hospitals” in Beijing, and to ascertain the apparent root causes for the pervasive degree of overcrowding in these EDs. Methods This is a multicenter cross-sectional study. The studied population included all ED patients from 18 metropolitan teaching hospital EDs in Beijing for calendar years 2013 and 2014. Patient characteristics, and the primary reasons that these patients sought care in these EDs, are described. Results The total numbers of annual emergency visits were 1,554,387 and 1,615,571 in 2013 and 2014, respectively. High acuity cases accounted for 4.6% and 5.5% of the total annual emergency visits in 2013 and 2014, respectively. The percentage of patients placed into “Observation” beds, which were created to accommodate patients deemed to have problems too complex to be treated in an inpatient bed, or to accommodate patients simply needing chronic care, was 11.9% and 13.1% in 2013 and 2014, respectively. The ED-boarded patients accounted for 2.71% and 2.6% of the total annual emergency visits in 2013 and 2014, respectively. The average waiting time to admit the ED-boarded patients was 37.1 h and 36.2 h in 2013 and 2014, respectively. Respiratory symptoms were the most common presenting complaints, and an upper respiratory infection was the most common ED diagnosis. Patients who had pneumonia or various manifestations of end-stage diseases, such as advanced dementia or multiple organ dysfunction, were the most common characteristics of patients who had stays in “Observation” units. Conclusions One principal reason for ED crowding in Beijing lies in the large numbers of patients who persist in the expectation of receiving ongoing care in the ED for minor illnesses. However, as is true in many nations, one of the other most important root causes of ED crowding is “access block,” the inability to promptly move patients deemed by emergency physicians to need inpatient care to an inpatient bed for that care. However, in our system, another challenge, not widely described as a contributor to crowding in other nations, is that doctors assigned to inpatient services have been empowered to refuse to admit patients perceived to have overly “complex” needs. Further, patients with multisystem illnesses or end-stage status, who need ongoing chronic care to manage activities of daily living, have begun to populate Beijing EDs in increasing numbers. This is an issue with various root causes.

Mechanical Circulatory Support in Chronic Total Occlusion Percutaneous Coronary Intervention: Insights from a Multicenter U.S. Registry

Abstract: OBJECTIVE To study outcomes with use of percutaneous mechanical circulatory support (MCS) devices in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS We examined characteristics and outcomes of 1598 CTO-PCIs performed from 2012-2017 at 12 high-volume centers. RESULTS Patient age was 66 ± 10 years; 86% were men. An MCS device was used electively in 69 procedures (4%) and urgently in 22 procedures (1%). The most commonly used elective MCS device was Impella 2.5 or CP (62%). Compared to patients without elective MCS, patients with elective MCS had higher prevalence of prior heart failure (55% vs 29%; P<.001), prior coronary artery bypass graft surgery (49% vs 35%; P=.02), and lower left ventricular ejection fraction (34 ± 14% vs 50 ± 14%; P<.001). MCS patients had a higher prevalence of moderate/ severe calcification (88% vs 55%; P<.001) and higher J-CTO scores (3.1 ± 1.2 vs 2.6 ± 1.2; P<.01), and a greater proportion underwent retrograde crossing attempts (55% vs 39%; P<.01). Despite more complex characteristics in MCS patients, technical success rates (88% vs 87%; P=.70) and procedural success rates (83% vs 87%; P=.32) were similar in the two groups. Use of elective MCS was associated with longer procedure and fluoroscopy times, and higher incidences of in-hospital major adverse cardiovascular events (8.7% vs 2.5%; P<.01) and bleeding (7.3% vs 1.0%; P<.001). CONCLUSION Elective MCS was used in 4% of patients undergoing CTO-PCI. Despite more complex clinical and angiographic characteristics, elective use of MCS in high-risk patients is associated with similar technical and procedural success rates, but higher risk of complications, compared to cases without elective MCS.

Chronic Illness with Complexity: Association With Self-Perceived Burden and Advance Care Planning

Abstract: The present study examines how different chronic illnesses and mental illness comorbidity (chronic illness with complexity [CIC]) associate with components of advance care planning (ACP). We also explore the role self-perceived burden plays in the relationship between illness and ACP. Data were gathered from a cross-sectional survey of 305 elderly participants from the New Jersey End-of-Life study. Participants with diabetes and those with cardiovascular disease (CVD) are less likely, while participants with CIC are more likely, to plan for the end-of-life. Participants with diabetes are less likely to make formal plans, whereas those with CVD are less likely to hold informal discussions. CIC is associated with increased odds of having an advance directive, but no other form of ACP. Self-perceived burden did not appear to be the gateway by which illness groups differentially engaged in ACP. Future research should investigate what aspects of illnesses drive ACP.

Point-of-Care Ultrasonography Findings and Care Use Among Patients Undergoing Ultrasound-Guided Shoulder Injections.

Abstract: OBJECTIVE The aims of the study were to assess the overall reduction of pain in patients undergoing ultrasound-guided shoulder injections and to characterize the preinjection point-of-care ultrasound findings and use of clinical services postinjection including the use of magnetic resonance imaging and surgeries. DESIGN Data of 172 patients who underwent ultrasound-guided subacromial subdeltoid injection or glenohumeral joint injection were reviewed for preinjection point-of-care ultrasound findings, change in pain intensity at 2 mos from baseline, and use of care at 6 mos' postinjection. Pain intensity was measured by the numeric rating scale and a dichotomous report of global impression of significant improvement in pain. Responders were defined as those with 50% or more reduction in numeric rating scale or those with global impression of 50% or more improvement. RESULTS There were 141 responders among the 172 patients analyzed. Full-thickness rotator cuff tears were higher in the ultrasound-guided subacromial subdeltoid injection group when compared with the glenohumeral joint injection group (P = 0.038) and abnormal bicipital tendon findings higher in the glenohumeral joint injection group (P = 0.016). There were no significant differences in specific abnormal U findings between responders versus nonresponders. Twelve patients had a shoulder magnetic resonance imaging and four patients underwent operative interventions after the injection. CONCLUSIONS Overall pain reduction after ultrasound-guided shoulder injections was favorable in the short term. There was no specific preinjection point-of-care ultrasound findings associated with clinical pain reduction after injection. Additional imaging and operative intervention after ultrasound-guided shoulder injections seemed to be relatively low.

Compositions for the treatment of cancer, and methods for testing and using the same

Abstract: A composition comprising leukotoxin proteins isolated from a bacterium is provided. In this composition, greater than 85% of the leukotoxin proteins are chemically modified at a basic amino acid residue, and the proteins induce cell death in myeloid leukocytes, while remaining substantially non-toxic to lymphoid leukocytes, lymphocytes, and red blood cells. Also provided is a method of selectively inducing cell death in myeloid leukocytes. The method comprises contacting the myeloid leukocytes with a composition comprising leukotoxin proteins. These leukotoxin proteins may be isolated from the NJ4500 strain of Actinobacillus actinomycetemcomitans. A method of purifying leukotoxin protein from the NJ4500 strain of Actinobacillus actinomycetemcomitans is also provided, as well as an assay that allows for the rapid determination of the activity of a given drug against leukemic cells either taken from a patient or derived from a cell line. The assay is performed in the presence of whole blood or serum.

Sleep after TBI: How the TBI Model Systems have advanced the field.

Abstract: Background Identification and management of comorbidities in TBI has become an increasing focus for optimizing TBI outcomes. Recent meta-analyses highlight sleep disturbance and sleep disorders following TBI (Mathias & Alvaro, 2012). Improving the recognition and treatment of sleep disorders in TBI should be a central focus of rehabilitation. The Traumatic Brain Injury Model System (TBIMS) has created an infrastructure allowing multi-center investigations into sleep dysfunction in those who have had a moderate to severe TBI and received inpatient rehabilitation. Objective This paper will describe the 1) infrastructure used to advance sleep dysfunction/disorders research following TBI, 2) preliminary findings from these studies, and 3) repository of data which can be accessed for secondary analyses by investigators outside of the TBIMS infrastructure. Methods Two internal mechanisms allow investigators at TBIMS sites to collaborate on projects of shared interest: Research Modules and Special Interest Groups (SIG). Results To date, five studies have resulted from the TBIMS collaborative process focusing on insomnia, circadian disruption, and sleep apnea. Conclusions Future directions for the SIG include continued development of available knowledge and understanding of the multidimensional factors that contribute to TBI-related sleep disturbance, optimal assessment tools, effectiveness of available treatments, and treatment compliance in this population.

ACMT Position Statement: Alternative or Contingency Countermeasures for Acetylcholinesterase Inhibiting Agents

Abstract: First responders and health care providers must prepare to provide care for patients poisoned by acetylcholinesterase (AchE) inhibitor chemical warfare agents or pesticides. However, pre-deployed medical countermeasures (MCMs) may not be sufficient due to production and delivery interruption, rapid depletion of contents during a response, expiration of MCM components, or lack of local availability of approved MCMs. To augment supplies of community-based and forward-deployed nerve agent countermeasures, the American College of Medical Toxicology (ACMT) supports several strategies: (1) The use of expired atropine, diazepam, and pralidoxime auto-injectors and vials if non-expired drugs are unavailable; and (2) Investigation, development, and identification of alternative countermeasures—commonly stocked drugs that are not approved for nerve agent poisoning but are in the same therapeutic class as approved drugs.

An Update on the Therapeutic Potential of Stem Cells

Abstract: The seeming setbacks noted for stem cells underscore the need for experimental studies for safe and efficacious application to patients. Both clinical and experimental researchers have gained valuable knowledge on the characteristics of stem cells, and their behavior in different microenvironment. This introductory chapter focuses on adult mesenchymal stem cells (MSCs) based on the predominance in the clinic. MSCs can be influenced by inflammatory mediators to exert immune suppressive properties, commonly referred to as "licensing." Interestingly, while there are questions if other stem cells can be delivered across allogeneic barrier, there is no question on the ability of MSCs to provide this benefit. This property has been a great advantage since MSCs could be available for immediate application as "off-the-shelf" stem cells for several disorders, tissue repair and gene/drug delivery. Despite the benefit of MSCs, it is imperative that research continues with the various types of stem cells. The method needed to isolate these cells is outlined in this book. In parallel, safety studies are needed; particularly links to oncogenic event. In summary, this introductory chapter discusses several potential areas that need to be addressed for safe and efficient delivery of stem cells, and argue for the incorporation of microenvironmental factors in the studies. The method described in this chapter could be extrapolated to the field of chimeric antigen receptor T-cells (CAR-T). This will require application to stem cell hierarchy of memory T-cells.

Patient knowledge of STI testing in an urban clinic.

Abstract: Objective To determine whether patients attending an urban STI clinic can accurately identify the STIs for which they were tested. Methods Participants completed a self-administered survey assessing demographics, reason for visit, perceived STI testing performed, and patient satisfaction. Chart review was conducted for verification of STI testing. Results 40.7% of participants were able to correctly identify the STIs for which they had been tested. Education level greater than a high school diploma was significantly associated with a patient's ability to correctly identify tests performed. Conclusions Patients presenting to STI clinics are generally unaware of which STI tests were done. Providers performing STI testing should inform patients of all tests performed, as well as common STIs for which they have not been tested.

Disseminated Granulomatous Disease from Intravesical Instillation of Bacillus Calmette-Guerin.

Abstract: Intravesical instillation of Bacillus Calmette-Guerin is one of the standard treatment options for superficial bladder cancer. While Bacillus Calmette-Guerin therapy is usually well tolerated with most patients experiencing only cystitis, in rare cases, it can lead to disseminated granulomatous disease. We present a case of a 72-year-old man with disseminated granulomatous disease from intravesical BCG instillation whose treatment was complicated by antimycobacterial drug toxicity.

Laudáció a szülésznőknek. Bábák és a gyermekágyi láz

Abstract: Originally published in the Hungarian Postgraduate Journal of Gynecology and Obstetrics (2016; 18: 209-2013). Reprint with the contribution and permission of the Professional Publishing Hungary Kft., Budapest. Orv Hetil. 2018; 159(26): 1079-1083.

Potential risk of clonally expanded amnion mesenchymal stem cell transplants in contused spinal cords.

Abstract: Objective Mesenchymal stem/stromal cells (MSC) promote recovery after spinal cord injury (SCI) using adult bone marrow MSC (BM-MSC). Newborn tissues are a convenient source of MSC that does not involve an invasive procedure for cell collection. In this study the authors tested the effects of rat amnion MSC clone (rAM-MSC) in SCI. Methods We tested intra-parenchymal injection of a GFP+ rat rAM-MSC clone derived from E18.5 rats in rat SCI and measured behavioral recovery (BBB scores), histology and X-ray opacity. Expression of aggrecan was measured in culture after treatment with TGFs. Results Injection of rAM-MSC after SCI did not improve BBB scores compared to control vehicle injections; rather they reduced scores significantly over 6 weeks. Spinal cords injected with rAM-MSC were hard in regions surrounding the SCI site, which was confirmed by X-ray opacity. Whole mount imaging of these cords showed minimal tissue loss in the SCI site that occurred in SCI controls, and persistence of GFP+ rAM-MSC. Mason's Trichrome staining of tissue sections showed more intense staining for extracellular matrix (ECM) surrounding and extending beyond the SCI site with injections of rAM-MSC but not in controls. In response to TGF-s treatment in culture, chondrogenic aggrecan was expressed at higher levels in rAM-MSC than in rBM-MSC, suggesting that the upregulation of TGF-s in SCI sites may promote chondrogenic differentiation. Conclusion Acute injection after SCI of a clonally expanded rAM-MSC resulted in aberrant differentiation towards a chondrocytic phenotype that disrupts the spinal cord and inhibits behavioral recovery after SCI. It will be critical to ensure that injection of extensively expanded neonatal cells do not differentiate aberrantly in traumatic CNS tissue and disrupt recovery.