Robert Wood Johnson University Hospital
  • New Brunswick, United States
Recent publications
Laminin polymerization is the major step in basement membranes assembly. Its failures cause laminin N-terminal domain lamininopathies including Pierson syndrome. We have employed cryo-electron microscopy to determine a 3.7 Å structure of the trimeric laminin polymer node containing α1, β1 and γ1 subunits. The structure reveals the molecular basis of calcium-dependent formation of laminin lattice, and provides insights into polymerization defects manifesting in human disease. In this work the authors report the cryo-EM structure of the laminin polymer node and reveal the molecular basis of calcium-dependent formation of laminin lattice. The work provides insights into laminin polymerization defects manifesting in human disease.
Background Greater attainment of ideal cardiovascular health (ICH) and lower serum aldosterone are associated with a lower diabetes risk. Higher levels of ICH are associated with lower aldosterone. The mediational role of aldosterone in the association of ICH with incident diabetes remains unexplored. Thus, we examined the mediational role of aldosterone in the association of 5 ICH components (smoking, diet, physical activity, body mass index [BMI], and cholesterol) and incident diabetes. Additionally, we investigated the mediational role of glucose and blood pressure (BP) in the association of aldosterone with incident diabetes in an African American (AA) cohort. Methods We conducted a prospective cohort analysis among AA adults, aged 21–94 years, in the Jackson Heart Study. Data on ICH, aldosterone, and cardiometabolic risk factors were collected at exam 1 (2000–2004). Diabetes (fasting glucose ≥ 126 mg/dL, physician diagnosis, use of diabetes drugs, or glycated hemoglobin ≥ 6.5%) was assessed at exams 1 through 3 (2009-2012). ICH metrics were defined by American Heart Association 2020 goals for smoking, dietary intake, physical activity, BMI, total cholesterol, BP and glucose. The number of ICH metrics attained at exam 1, excluding BP and fasting glucose, were summed (0–2, vs. 3+). R Package Mediation was used to examine: 1) The mediational role of aldosterone in the association of ICH with incident diabetes; and 2) the mediational role of BP and glucose in the association of aldosterone with incident diabetes. Results Among 2,791 participants (mean age: 53±12, 65% female) over a median of 7.5 years, there were 497 incident diabetes cases. Risk of incident diabetes was 37% (HR: 0.63, 95%CI: 0.47, 0.84) lower in 3+ ICH category compared to 0-2 ICH category. Aldosterone mediated 6.98% (95% CI: 1.8%, 18.0%) of the direct effect of ICH on incident diabetes. A 1-unit increase in log-aldosterone was associated with a 44% higher risk of diabetes (HR 1.44, 95%CI 1.25-1.64). BP and glucose mediated 16.3% (95% CI: 7.0%, 31.0%) and 19.7% (95% CI: 6.5%, 34.0%) of the association of aldosterone with incident diabetes, respectively. Conclusion Aldosterone is a mediator of the association of ICH with incident diabetes, whereas BP and glucose are mediators of the association of aldosterone with incident diabetes, emphasizing the importance of the renin-angiotensin-aldosterone system and ICH in lowering risk of diabetes in AA populations.
Purpose of Review The goal of this review is to examine currently available risk drug decision support strategies including medication characteristics in reducing the risk of medication-related iatrogenesis in the older adult. Older adults are at a significantly increased risk of medication-related iatrogenesis due to a myriad of factors: polypharmacy, multiple prescribers, pharmacokinetic and pharmacodynamic changes of aging, disease burden, and more. With a still-increasing proportion of Medicaid-aged patients in the US healthcare system, it is imperative to direct limited healthcare resources to have the highest impact on risk reduction. Recent Findings Recent research shows many strategies are available to identify the risk of medication-related iatrogenesis in the older adult, but there is a dearth of literature supporting strategies to reduce risk thereafter. Such strategies include medication class-specific risk scores, tools to identify potentially inappropriate medications, risk stratification tools, prescribing cascade identification, and preemptive pharmacogenomic testing. Summary There is currently not enough literature to achieve consensus on the best strategy to reduce the risk of medication-related iatrogenesis in this population. There are innumerable tools to identify high-risk patients and most are only able to address one or two facets of this complex problem. Risk mitigation studies are extremely heterogenous in their choice of outcomes and method of risk reduction; future research will need to become more standardized and study larger populations of older adults.
Introduction: Aneurysms of persistent primitive trigeminal artery (PPTAAs) are increasingly reported and commonly managed by endovascular (EN) techniques. There are no systematic reviews or meta-analyses which analyse outcomes and complications of treatment modalities for PPTAAs. We aim to highlight the change in trend of management of PPTAAs and to identify clinical and radiological parameters which may influence management paradigms. Methodology: A systematic search of literature was done in PubMed, Embase, Google Scholar, Cochrane library and Medline using keywords 'persistent primitive trigeminal artery', 'aneurysms', 'embolization', 'surgical clipping', etc. Only cases reporting aneurysms of PPTA were included. Three subgroups, such as conservative, open surgical (OS) and EN interventional, were studied for outcome evaluation. In the EN subgroup, relation of clinical and radiological parameters with outcome (complete/partial occlusion) was analysed using Microsoft Excel Data Analysis ToolPak. Results: Of the 101 articles found eligible for assessment, 54 were analysed quantitatively. Mortality in the conservative group was 12.5% and OS group was 9.09%. After EN treatment, complete angiographic occlusion was seen in 88.89% PPTAAs and 5.5% warranted retreatment. In the EN subgroup, location (p=0.17), shape (p=0.69), Saltzman circulation (p=0.26) or status of rupture (p=0.08) did not significantly impact angiographic occlusion outcome. Multivariate regression analysis showed 6.6% influence of independent variables, that is, age, gender, aneurysm location, side, shape (saccular/fusiform), rupture status and type of Saltzman circulation on aneurysm occlusion outcome [F(7,27) =1.34] (p=0.27). Total mortality reported in the EN group was 8.57%. Conclusion: Clinical or radiological parameters do not influence angiographic occlusion outcome. Although EN techniques are successful, meticulous reporting of outcomes and complications is important.
Patients receiving palliative care (PC) can present with or develop a host of urological needs or complications. These needs can include attention to sexual health, urinary incontinence, genitourinary bleeding, and urinary tract obstruction by benign, malignant, or urinary stone diseases. These varied conditions require that PC clinicians understand invasive and noninvasive medical, surgical, and radiation options for treatment. This article, written by a team of urologists, geriatricians, and PC specialists, offers information and guidance to PC teams in an accessible "Top Ten Tips" format to increase comfort with and skills around assessment, evaluation, and specialist referral for urological conditions common in the PC setting.
Sarcomatoid hepatocellular carcinoma (SHCC) is a rare variant of liver cancer that lacks treatment options. The IMbrave trail demonstrated the efficacy of atezolizumab and bevacizumab (A + B) in patients with unresectable hepatocellular carcinoma but excluded patients with sarcomatoid variants. Herein, we describe a case of disease control achieved using the IMbrave regimen in a patient with sarcomatoid hepatocellular carcinoma.
Research participation by minority individuals is critical to address health disparities, and lack of trust in research/researchers (TIR) is a significant barrier to participation. Few existing studies examine the relationship between level of TIR and hypothetical research participation in a sufficiently diverse sample. The survey was conducted among White, Black, Hispanic, and Asian community‐dwelling adults in New Jersey (N = 293 between October 2020 and January 2022). A 12‐item TIR measure based on published scales was developed with input from community partners. Respondents were also asked if they would participate in different types of research (i.e. survey, blood draw, medication study). Exploratory and confirmatory factor analysis was conducted to identify the underlying structure of TIR. Cluster analysis on research participation was conducted to determine patterns. Regression‐based mediation analysis was done to determine relationship between race/ethnicity, TIR, and hypothetical research participation. Responses were collected from 293 adults, with 38% reporting ages of 55 years or older. Factor analysis revealed three main factors on 9‐items related to Researchers as Fiduciaries (lowest score in Chinese adults), Equity in Research (highest score in White adults), and Transparency in Research. Cluster analysis revealed two major clusters: one cluster only willing to participate in anonymous health‐related surveys, and the other highly willing to participate in studies involving blood tests and genetic analysis. Only Chinese race/ethnicity was associated with lower Researchers as Fiduciaries scores (B = ‐0.54, 95% CI‐0.85 to ‐0.23, p = 0.0007), with the mediation model (Sobel Z of ‐3.22, p<0.001, k2 = 0.13) showing a direct effect of ‐0.64 (95% CI ‐1.36 to 0.08, p = 0.08) and indirect effect of ‐0.69 (95% CI ‐1.06 to ‐0.32, p = 0.001) from Chinese race/ethnicity on participation willingness. Chinese respondents showed low trust in researchers to serve as their fiduciaries, which mediated their low willingness to participate in research involving more than health‐related surveys. All non‐White groups also endorsed inequity in treatment by researchers, but Hispanic and Black adults were still likely to be interested in minimal risk (blood draw, genetic analysis) research participation. These findings call for community‐specific approaches to enhance biomedical research participation among non‐White adults.
While the COVID-19 pandemic disrupted healthcare delivery everywhere, persons with carceral system involvement and opioid use disorder (OUD) were disproportionately impacted and vulnerable to severe COVID-associated illness. Carceral settings and community treatment programs (CTPs) rapidly developed protocols to sustain healthcare delivery while reducing risk of COVID-19 transmission. This survey study assessed changes to OUD treatment, telemedicine use, and re-entry support services among carceral and CTPs participating in the National Institute on Drug Abuse (NIDA)-funded study, Long-Acting Buprenorphine vs. Naltrexone Opioid Treatments in Criminal Justice System-Involved Adults (EXIT-CJS) study. In December 2020, carceral sites (n = 6; median pre-COVID 2020 monthly census = 3468 people) and CTPs (n = 7; median pre-COVID 2020 monthly census = 550 patients) participating in EXIT-CJS completed a cross-sectional web-based survey. The survey assessed changes pre- (January-March 2020) and post- (April-September 2020) COVID-19 in OUD treatment, telemedicine use, re-entry supports and referral practices. Compared to January-March 2020, half of carceral sites (n = 3) increased the total number of persons initiating medication for opioid use disorder (MOUD) from April-September 2020, while a third (n = 2) decreased the number of persons initiated. Most CTPs (n = 4) reported a decrease in the number of new admissions from April-September 2020, with two programs stopping or pausing MOUD programs due to COVID-19. All carceral sites with pre-COVID telemedicine use (n = 5) increased or maintained telemedicine use, and all CTPs providing MOUD (n = 6) increased telemedicine use. While expansion of telemedicine services supported MOUD service delivery, the majority of sites experienced challenges providing community support post-release, including referrals to housing, employment, and transportation services. During the COVID-19 pandemic, this small sample of carceral and CTP sites innovated to continue delivery of treatment for OUD. Expansion of telemedicine services was critical to support MOUD service delivery. Despite these innovations, sites experienced challenges providing reintegration supports for persons in the community. Pre-COVID strategies for identifying and engaging individuals while incarcerated may be less effective since the pandemic. In addition to expanding research on the most effective telemedicine practices for carceral settings, research exploring strategies to expand housing and employment support during reintegration are critical.
Adrenal hemorrhage (AH) is associated with trauma, acute stress, sepsis, coagulopathy, pregnancy, neonatal stress, and underlying adrenal masses, which can include metastases, pheochromocytomas, adrenocortical cancers, or hematomas. However, the literature on nontraumatic AH secondary to an adenoma in the setting of chronic anticoagulation is limited. We present a case report of a patient found to have AH from an incidental adrenal adenoma associated with the use of warfarin in the setting of a recent history of pulmonary embolism requiring anticoagulation. In a patient who presents with AH while on anticoagulation, initial management should include reversal of coagulopathy, supportive care with serial hematocrits and blood transfusions as necessary, and biochemical workup to assess for functional tumors. However, aggressive surgical management with adrenalectomy should ideally follow for those patients who will require long-term anticoagulation to minimize future risk for rebleeding.
Background Despite multiple studies indicating a low prevalence of bacterial coinfection in coronavirus disease 2019 (COVID-19) patients, the majority of hospitalized COVID-19 patients receive one or more antibiotics. Patients with coinfection usually have multiple risk factors and poor clinical outcomes. Methods A retrospective case control study was conducted comparing clinical characteristics and antimicrobial use in hospitalized adult COVID-19 patients with bacterial co-infections vs. randomly selected patients without co-infections (matched on month of admission). The study was conducted at three hospitals within the Montefiore Medical Center, Bronx, NY between March 1, 2020 and October 31, 2020. A multivariable logistic regression model was developed to assess the relationship of each predictor variable with coinfection status. Secondary outcomes included hospital mortality, antibiotic days of therapy (DOT), and C. difficile infection. Results A total of 150 patients with coinfection and 150 patients without co-infection were included in the analysis. Table 1 summarized baseline characteristics and risk factors. The multivariable logistic regression model indicated that presence of a central line (OR=5.4, 95% CI: 2.7-11.1), prior antibiotic exposure within 30 days (OR=5.3, 95% CI: 2.8-10.0), prior ICU admission (OR=3.6, 95% CI: 1.7-7.6), steroid use (OR=2.7, 95% CI: 1.4-4.9), and any comorbid condition (OR=2.7, 95% CI: 1.4-5.2) were significantly associated with the development of coinfection (table 2). Mortality was higher in patients with coinfection (56% vs. 11%, p < 0.0001) (table 3). Average antibiotic DOT was 10.5 in coinfected patients compared to 4 in non-coinfected patients, (p < 0.0001). Forty-one percent of coinfected patients had a multidrug resistant organism isolated. C. difficile rate was higher in coinfected patients (4% vs. 0%, p=0.03). Conclusion As the healthcare community contends with a 3rd year of COVID-19 pandemic, understanding risk factors most predictive of bacterial coinfection can guide empiric antimicrobial therapy and targeted stewardship interventions. Ideally, co-infection risk scores are developed which may be useful for future inpatient surges. Disclosures Yi Guo, PharmD, BCIDP, Merck: Grant/Research Support Kelsie Cowman, MPH, Merck: Grant/Research Support.
According to the American College of Cardiology/American Heart Association (ACC/AHA) new cholesterol management guidelines in 2019, statin regimen was prescribed to only about 46.4% and 30% of diabetes (DM) patients and patients with atherosclerotic cardiovascular disease (ASCVD), respectively. Atherosclerotic cardiovascular disease accounts for most deaths and disabilities in North America. This study argues that a systematic approach to identifying targeted interventions to adhere to the statin regimen for ASCVD is sparse in previous studies. This study seeks to address the research gap. Besides, the study argues that the statin regimen could improve cholesterol management with the enablers of pharmacy, providers, electronic medical records (E.M.R.), and patients. It paves the way for future research on cardiovascular and statin regimens from different perspectives. Current study has adopted the Qualitative observation method. Accordingly, the study approached the charity care primary clinic serving a large population in the northeastern part of the United States, which constitutes the project’s setting. The facility has 51 internal medicine residents. The facility has E.H.R., which is used by the clinical staff. Besides, providers use electronic medication prescribing (E-Scribe). Four PDSA cycles were run in six months. Here, the interventions were intensified during each subsequent cycle. The interventions were then incorporated into routine clinical practice. Based on the observation, the study found a 25% relative improvement by six months based on the baseline data of the appropriate intensity statin prescription for patients with ASCVD or DM by medical resident trainees in our single-center primary care clinic. A total of 77% of cardiovascular disease patients were found to be on an appropriate statin dose at baseline. On the other hand, the proportion of patients with DM who were on proper dose statin was 80.4%. According to the study’s findings, PDSA could result in a faster uptake and support of the ACC/AHA guidelines. Evidence indicates that overmedication of persons at low risk and time constraints are some of the most significant impediments to the greater use of prescription medications. Proactive panel management can help improve statins’ use by ensuring they are used appropriately.
The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). “Cases of SCMR” is a case series hosted on the SCMR website ( https://www.scmr.org ) that demonstrates the utility and importance of CMR in the clinical diagnosis and management of cardiovascular disease. The COVID-19 Case Collection highlights the impact of coronavirus disease 2019 (COVID-19) on the heart as demonstrated on CMR. Each case in series consists of the clinical presentation and the role of CMR in diagnosis and guiding clinical management. The cases are all instructive and helpful in the approach to patient management. We present a digital archive of the 2021 Cases of SCMR and the 2020 and 2021 COVID-19 Case Collection series of nine cases as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar literature search engine.
Patients with hematologic malignancies have poor outcomes from COVID infection and are less likely to mount an antibody response after COVID infection. This is a retrospective study of adult lymphoma patients who received the COVID vaccine between 12/1/2020 and 11/30/2021. The primary endpoint was a positive anti-COVID spike protein antibody level following the primary COVID vaccination series. The primary vaccination series was defined as 2 doses of the COVID mRNA vaccines or 1 dose of the COVID adenovirus vaccine. Subgroups were compared using Fisher's exact test, and unadjusted and adjusted logistic regression models were used for univariate and multivariate analyses. A total of 243 patients were included in this study; 72 patients (30%) with indolent lymphomas; 56 patients (23%) with Burkitt's, diffuse large B-cell lymphoma (DLBCL), and primary mediastinal B-cell lymphoma (PMBL) combined; 55 patients (22%) with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL); 44 patients (18%) with Hodgkin and T-cell lymphomas (HL/TCL) combined; 12 patients (5%) with mantle cell lymphoma; and 4 patients (2%) with other lymphoma types. One-hundred fifty-eight patients (65%) developed anti-COVID spike protein antibodies after completing the primary COVID vaccination series. Thirty-eight of 46 (83%) patients who received an additional primary shot and had resultant levels produced anti-COVID spike protein antibodies. When compared to other lymphoma types, patients with CLL/SLL had a numerically lower seroconversion rate of 51% following the primary vaccination series whereas patients with HL/TCL appeared to have a robust antibody response with a seropositivity rate of 77% (p = 0.04). Lymphoma patients are capable of mounting a humoral response to the COVID vaccines. Further studies are required to confirm our findings, including whether T-cell immunity would be of clinical relevance in this patient population.
Cocaine acts by inhibiting plasma membrane dopamine transporter (DAT) function as well as altering its surface expression. The precise manner and mechanism by which cocaine regulates DAT trafficking, especially at neuronal processes, are poorly understood. In this study, we engineered and validated the use of DAT-pHluorin for studying DAT localization and its dynamic trafficking at neuronal processes of cultured mouse midbrain neurons. We show that unlike neuronal soma and dendrites, which contain majority of the DATs in weakly acidic intracellular compartments, axonal DATs at both shafts and boutons are primarily (75%) localized to the plasma membrane, while large varicosities contain abundant intracellular DAT within acidic intracellular structures. We also demonstrate that cocaine exposure leads to a Synaptojanin1-sensitive DAT internalization process followed by membrane reinsertion that lasts for days. Thus, our study reveals the previously unknown dynamics and molecular regulation for cocaine-regulated DAT trafficking in neuronal processes.
Twinkle is the ring-shaped replicative helicase within the human mitochondria with high homology to bacteriophage T7 gp4 helicase-primase. Unlike many orthologs of Twinkle, the N-terminal domain (NTD) of human Twinkle has lost its primase activity through evolutionarily acquired mutations. The NTD has no demonstrated activity thus far; its role has remained unclear. Here, we biochemically characterize the isolated NTD and C-terminal domain with linker (CTD) to decipher their contributions to full-length (FL) Twinkle activities. This novel CTD construct hydrolyzes ATP, has weak DNA unwinding activity, and assists DNA Polymerase γ (Polγ)-catalyzed strand-displacement synthesis on short replication forks. However, CTD fails to promote multi-kilobase length product formation by Polγ in rolling-circle DNA synthesis. Thus, CTD retains all the motor functions but struggles to implement them for processive translocation. We show that NTD has DNA binding activity, and its presence stabilizes Twinkle oligomerization. CTD oligomerizes on its own, but the loss of NTD results in heterogeneously-sized oligomeric species. The CTD also exhibits weaker and salt-sensitive DNA binding compared to FL Twinkle. Based on these results, we propose that NTD directly contributes to DNA binding and holds the DNA in place behind the central channel of the CTD like a ‘doorstop’, preventing helicase slippages and sustaining processive unwinding. Consistent with this model, mitochondrial single-stranded DNA binding protein (mtSSB) compensate for the NTD loss and partially restore kilobase length DNA synthesis by CTD and Polγ. The implications of our studies are foundational for understanding the mechanisms of disease-causing Twinkle mutants that lie in the NTD.
Background: Radical antegrade modular pancreatosplenectomy (RAMPS) has oncologic superiority compared to a standard distal pancreatectomy (DP). For tumors invading into the adrenal gland, a posterior RAMPS takes the left adrenal gland en bloc with the pancreas specimen. The aim of this analysis is to determine whether addition of adrenalectomy alters the outcomes of DP. Methods: The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) Procedure-Targeted Pancreatectomy database was accessed from 2014 to 2019. Patients with pancreatic ductal adenocarcinoma (PDAC) undergoing posterior RAMPS were compared to patients having a standard DP. 30-day outcomes were analyzed using multivariable regression. Results: 3467 PDAC patients underwent DP; 159 (4.6%) also had an adrenalectomy. Posterior RAMPS patients had higher T stage (T3-4 77% vs. 58%, p < 0.01). On multivariable analysis, posterior RAMPS patients had worse perioperative outcomes including more transfusions (OR 2.78, p < 0.01), serious morbidity (OR 1.45, p = 0.04), prolonged hospital stay (OR 1.36, p < 0.05), and less optimal pancreatic surgery (OR 0.61, p < 0.01). Conclusion: Radical antegrade modular pancreatosplenectomy with adrenalectomy (posterior RAMPS) is associated with worse perioperative outcomes compared to a standard distal pancreatectomy. Improved oncologic outcomes must be weighed against higher perioperative morbidity when selecting patients for this more extensive surgical resection.
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274 members
Michel Kahaleh
  • Department of Gastroenterology
Ephrem O Olweny
  • Surgery / Urology
Eric L Hargreaves
  • Division of Neurosurgery
Surasak Puvabanditsin
  • Department of Pediatrics
Howard F Fine
  • Department of Ophthalmology
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New Brunswick, United States