Energy and Greenhouse Gas Emission Savings Associated with Implementation of an Abbreviated Cardiac MRI Protocol.

Supplemental material is available for this article. See also the article by Lenkinski and Rofsky in this issue. See also the article by McKee et al in this issue.

Botulinum Toxin for the Management of Parkinson's Disease: A Systematic Review.

Parkinson's disease (PD) is a terminal, debilitating neurodegenerative disorder typically affecting individuals over 60. It is associated with various conditions that drastically affect the patient's quality of life (QoL). Although there is no cure for PD, its symptoms can be significantly improved and even resolved through different treatments. Mainstay treatments for PD include levodopa combined with carbidopa, dopamine agonists, and even deep brain stimulation (DBS) of the subthalamic nucleus. New treatment methods have emerged, such as botulinum toxin (BoNT), which further improve symptoms and, thus, the QoL of patients with PD. Botulinum toxin is a potent neurotoxin produced by Clostridium botulinum that typically causes descending paralysis by suppressing acetylcholine secretion. Serotypes used to treat various disorders include serotype A (BoNT-A) and serotype B (BoNT-B). This paper aims to evaluate the outcomes of BoNT injection on different symptoms associated with PD. An extensive review using PubMed, ScienceDirect, and ProQuest articles concerning 'botulinum toxin and Parkinson's disease' was done per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, resulting in 23,803 articles. After applying strict inclusion and exclusion criteria, the total number of articles was finally 41. The results showed that movement disorders were a common occurrence in PD, consisting of tremors, dystonia, and freezing of gait (FOG), with tremors being the most common symptom. Tremors and dystonia were significantly improved following BoNT-A, correlating with significant improvements in various scales subjectively and objectively evaluating the symptoms and QoL. In contrast, FOG was not significantly improved by either BoNT-A or BoNT-B. Pain is associated with movement disorders such as PD and was the primary indication for the administration of BoNT; studies found pain and QoL were significantly improved following BoNT injection. Quality of life can also be affected by sialorrhea and overactive bladder, which often occur as the disease progresses. Injections of BoNT-A and BoNT-B were shown to significantly improve saliva production, flow rate, drooling frequency, voiding frequency, and urinary urge incontinence. Across all studies analyzed, it is evident that BoNT may have a significant effect on improving the QoL of patients suffering from PD. While research continues to find a cure or stop the progression of PD, it remains critical to continue focusing on improving patients' QoL. Future research should evaluate whether BoNT can be used to successfully treat other symptoms of PD, such as epiphora or constipation.

Outcomes and Readmissions after Left Atrial Appendage Occlusion in Octogenarians: A Contemporary Analysis.

INTRODUCTION AND OBJECTIVES: The outcomes of left atrial appendage occlusion (LAAO) with the Watchman device in octogenarians are unknown as this population was underrepresented in major clinical trials. This study aims at examining the causes and outcomes of readmission after LAAO. DESIGN: A retrospective cohort study based on the National Readmission Database in the United States. SETTINGS AND PARTICIPANT: Patients aged ≥80 years, admitted between January 2016 and December 2018, with the primary diagnosis of atrial fibrillation or flutter or who had LAAO were included in the study. Patients who died during index admission were excluded. METHODS: We used the National Readmission Database and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes to identify study participants. Data analysis was performed through Stata, version 17. Univariate and multivariate aggression analysis was used to adjust for confounders using Student t tests and χ2 tests. RESULTS: We identified 491,329 patients on anticoagulation (AC) and 2030 patients who underwent LAA closure. Neither group differed regarding hypertension, previous myocardial infarction, or valvular heart disease. All-cause readmissions were lower in the LAAO group at 45 days (adjusted P < .01). All-cause readmissions at 45 and 90 days were similar in both groups. There was an increase in gastrointestinal bleeding (GIB) readmissions in the LAAO at 45 (P < .01), 90 (P < .01), and 180 (P < .01) days. There was no difference in GIB readmission between the 2 groups. There was no also difference in stroke or intracranial hemorrhage rates between the 2 groups throughout the follow-up period. CONCLUSION AND IMPLICATIONS: In octogenarians who received LAAO, the rate of GIB increased during the first 6 months after the procedure; however, it was not different from that of AC after that. Special attention should be given to the antithrombotic regimens after LAAO to avoid bleeding in this vulnerable patient population.

Anti-diabetics and the Prevention of Dementia: A Systematic Review.

Type 2 diabetes mellitus (T2DM) is a worldwide epidemic that is only increasing as the years progress, and as of 2019, affecting over 37 million. T2DM is a chronic condition caused by reduced insulin secretion and increased insulin resistance. Due to insulin not operating at optimal conditions, blood glucose rises and remains high, thus disturbing metabolic hemostasis. Many complications can arise from T2DM, such as coronary vascular disease, kidney damage, eye damage, and, quite significantly, dementia. It is theorized that dementia from T2DM stems from the fact that the brain is susceptible to hyperglycemic conditions, which are promoted by the increase in insulin resistance of target cells in the central nervous system. This directly affects cognitive processes and memory, which correlates to decreased temporal and front lobes volume. The risk of diabetic complications can be minimized with therapeutic interventions such as oral-antidiabetic (OAD) agents and insulin. Several OADs are on the market, but the first-line agent is metformin, a biguanide that decreases glucose production and increases insulin sensitivity. This paper aims to determine if currently prescribed OADs can help slow cognitive decline and reduce the risk and incidence of dementia as a complication of T2DM. Studies found that, for the most part, all OADs except sulfonylureas (SU) significantly slowed the decline of cognitive function and reduced the risk and incidence of dementia. SU's were shown to increase the risk of dementia in most studies. Of all the OADs, thiazolidinediones may be the most beneficial drug class for reducing the risk of dementia in T2DM patients. Future research should focus on whether early intervention with specific classes of OADs can not only improve glycemic control, leading to decreased hyperglycemia but also prevent the build-up of damaged brain tissue and help to reduce the risk and incidence of dementia in patients with T2DM.

Characteristics and Outcomes of Early vs Late Initiation of Mechanical Circulatory Support in Non-Acute Myocardial Infarction related Cardiogenic Shock: An Analysis of the National Inpatient Sample Database.

Cardiogenic shock (CS) is significant cause of mortality. The use of mechanical circulatory support (MCS) in patients with non-acute myocardial infarction (Non-AMI) CS is lacking. We inquired data regarding the trends and outcomes early vs late initiation of MCS in non-AMI CS. We investigated National Inpatient Sample database between October 2015-December 2018, identifying hospitalizations with CS, either complicated by AMI or Non-AMI. Patients were divided into 2 cohorts, early initiation of MCS (<48 hours) and late initiation of MCS (>48 hours). The primary analysis included death within first 24 hours. A secondary analysis was adjusted after excluding patients who died in first 24 hours. A total of 85,318 patients with non-AMI-related CS with MCS placement were identified. Among this cohort, 54.6% (n=46,579) underwent early initiation of MCS within 48 hours, and 45.4% (n=38,739) underwent late initiation of MCS after 48 hours. In primary analysis, early MCS initiation was associated with more in-hospital mortality in primary outcome of all-cause hospital mortality (35.72% vs 27.63%, P<0.0001, OR 1.44, 95% CI: 1.40-1.49, P<0.0001), however, adjusted secondary analysis showed a statistically significant decrease in all-cause hospital mortality (23.63% vs 27.63%, P<0.0001, OR 0.80, 95% CI: 0.78-0.83, P<0.0001). In non-AMI-related CS and based on survival to 24 hours after admission, early initiation of MCS had statistically significant decrease in all-cause hospital mortality, with less incidence of vascular and renal complications, and shorter hospital stay. Late initiation of MCS was associated with a higher incidence of advanced therapies, including LVAD and transplant.

Meta-analysis Comparing Percutaneous Coronary Intervention With Coronary Artery Bypass Grafting for Non-ST Elevation Acute Coronary Syndrome in Patients With Multivessel or Left Main Disease.

Outcomes of patients presenting with non-ST-elevation acute coronary syndrome (NSTE-ACS) with multivessel coronary disease (MVD) and/or unprotected left main coronary artery disease (CAD) revascularized with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is not well defined. MEDLINE/PubMed and EMBASE/Ovid were queried for studies that investigated PCI vs CABG in this disease subset. The primary outcome was major cardiac adverse events (MACE) at 30 days and long-term follow-up (3-5 years). The final analysis included 9 studies with a total of 9299 patients. No significant difference was observed between PCI and CABG in 30 days MACE (risk ratio [RR] 0.96; 95% confidence interval [CI] 0.38-2.39, all-cause mortality, myocardial infarction, and stroke. A meta-regression analysis revealed patients with a history of PCI had higher risk of MACE with PCI as compared with CABG. At long-term follow-up, PCI compared with CABG was associated with higher risk of MACE (RR 1.52; 95% CI 1.28-1.81), myocardial infarction, and repeat revascularization, while no difference was observed in the risk of stroke and all-cause mortality. In patients with NSTE-ACS and MVD or unprotected left main CAD, no differences were observed in the clinical outcomes between PCI and CABG at 30 days follow-up. With long-term follow-up, PCI was associated with a higher risk of MACE.

Outcomes of Cardiac Arrest and Cardiopulmonary Resuscitation in Patients With Left Ventricular Assist Device; an Insight From a National Inpatient Sample.

BACKGROUND: Outcomes of patients with implanted left ventricular assist device (LVAD) implantation experiencing a cardiac arrest (CA) are not well reported. We aimed at defining the in-hospital outcomes of patients with implanted LVAD experiencing a CA. METHODS: The national inpatient sample (NIS) was queried using ICD9/ICD10 codes for patients older than 18 years with implanted LVAD and CA between 2010-2018. We excluded patients with orthotropic heart transplantation, biventricular assist device (BiVAD) implantation and do not resuscitate (DNR) status. RESULTS: A total of 93,153 hospitalisations between 2010 and 2018 with implanted LVAD were identified. Only 578 of these hospitalisations had experienced CA and of those, 173 (33%) hospitalisations underwent cardiopulmonary resuscitation (CPR). The mean age of hospitalisations that experienced a CA was 60.61±14.85 for non-survivors and 56.23±17.33 for survivors (p=0.14). The in-hospital mortality was 60.8% in hospitalisations with CA and 74.33% in hospitalisations in whom CPR was performed. In an analysis comparing survivors with non-survivors, non-survivors had more diabetes mellitus (DM) (p=0.01), and ischaemic heart disease (IHD) (p=0.04). Age, female sex, peripheral vascular disease and history of coronary artery bypass graft (CABG) were independently associated with increased mortality in our cohort. Also, ventricular tachycardia (VT) and CPR were independently associated with in-hospital mortality. During the study period, there was a significantly decreasing trend in performing CPR in LVAD hospitalisations with CA. CONCLUSION: In conclusion, age, female sex, peripheral vascular disease, history of CABG, VT and CPR were independently associated with in-hospital mortality in LVAD hospitalisations who experienced CA.

Echocardiography, lung ultrasound, and cardiac magnetic resonance findings in COVID-19: A systematic review.

BACKGROUND: The manifestations of COVID-19 as outlined by imaging modalities such as echocardiography, lung ultrasound (LUS), and cardiac magnetic resonance (CMR) imaging are not fully described. METHODS: We conducted a systematic review of the current literature and included studies that described cardiovascular manifestations of COVID-19 using echocardiography, CMR, and pulmonary manifestations using LUS. We queried PubMed, EMBASE, and Web of Science for relevant articles. Original studies and case series were included. RESULTS: This review describes the most common abnormalities encountered on echocardiography, LUS, and CMR in patients infected with COVID-19.

Meta-analysis of Safety and Efficacy of Anticoagulation versus no Anticoagulation in Octogenarians and Nonagenarians with Atrial Fibrillation.

INTRODUCTION: The role of anticoagulation in octogenarians and nonagenarians with atrial fibrillation (AF) is controversial due to the lack of evidence from randomized controlled trials (RCTs), owing to the under representation of these patients in clinical trials. AIM: In the present meta-analysis we aim at comparing the clinical benefits and risk of anticoagulation (AC) with no AC in octogenarians and nonagenarians. METHODS: We systematically searched MEDLINE/PubMed, EMBASE/Ovid, and Web of Science databases from the inception to October, 2020. Studies were eligible for inclusion if they met the following criteria: studies comparing AC with no AC in patients aged 80 or more for AF and reported thromboembolic events (TE) and bleeding outcomes. We used Mantel-Haenszel method with a Paule-Mandel estimator of Tau2 with Hartung Knapp-Sidik-Jonkman adjustment to estimate risk ratio (RR) with a 95% confidence interval (CI). Outlier analysis was used to adjust for statistical heterogeneity. RESULTS: A total of 10 observation studies and 1 RCT were included in the final analysis. There was no difference in the risk of TE with AC in octogenarians and nonagenarians compared with no AC, before [RR: 0.87, 95% CI 0.62-1.23, I2: 71%, GRADE confidence "very low"] and after [RR: 0.83, 95% CI 0.66-1.04, I2: 55.5%] adjusting for statistical heterogeneity among studies. In the unadjusted analysis, no difference in the risk of bleeding events was observed between both groups [RR: 1.05, 95% CI 0.62-1.77, I2: 86%, GRADE confidence "very low"]. After adjusting for heterogeneity, AC was associated with an increased risk of bleeding compared with those not receiving AC [RR: 1.57, 95% CI 1.44-1.71, I2: 0%]. AC in octogenarians was not associated with a net clinical benefit compared with no AC. CONCLUSIONS: This meta-analysis did not demonstrate any difference in the risk TE in octogenarians and nonagenarians with AF on AC vs. no AC, in both the adjusted and unadjusted analyses. Also, the risk of bleeding events in the unadjusted analysis was similar between both groups. The adjusted analysis showed an increased risk of bleeding in the AC group compared with no AC group. More data is needed to establish safety and efficacy of AC in this vulnerable patient population. The results of this analysis should be interpreted with caution due to the observational nature of most studies included, and the only RCT reported lower rates of TE and similar risk of bleeding.

The association between bronchial asthma and periodontitis: A case-control study in Jordan.

OBJECTIVE: Our aim is to study the association between bronchial asthma (BA) and periodontitis in Jordan. METHODS: A case control study of 260 subjects; 130 with BA and 130 without BA (controls) were recruited at a university hospital in Jordan. BA cases were physician-diagnosed and on anti-asthma medications for 12 months. Periodontitis was defined as the presence of ≥ 4 teeth with ≥ 1 site with probing pocket depth (PPD) ≥ 4 mm and clinical attachment level (CAL) ≥ 3 mm. RESULTS: Mean age of participants was 45.3 years (range, 18-65) and 58.1% were females. Patients with BA had lower education and tended to live in rural areas. Periodontitis was present in 52 (40.0%) patients with BA and 26 (20.0%) in the control group, p < 0.005. Binary logistic regression indicated that patients with BA were more likely to have periodontitis than controls [adjusted odd ratio (OR) = 2.91, 95% CI (1.39-6.11), p = 0.005]. Patients with BA had higher percentage of sites with: PPD ≥ 3 mm, CAL ≥ 3 mm, and CAL ≥ 4 mm than controls, p < 0.05. The risk of periodontitis [OR = 5.27, 95% CI (1.59-17.51)] and CAL ≥ 3 mm were higher in patients on oral corticosteroids compared to inhaled corticosteroids, p < 0.05. CONCLUSIONS: Adult Jordanians with bronchial asthma are at higher risk of periodontitis, particularly those on oral corticosteroids. Large and longitudinal studies are needed to better understand this significant association.

Uropathogenic E. coli (UPEC) Infection Induces Proliferation through Enhancer of Zeste Homologue 2 (EZH2).

UNLABELLED: Host-pathogen interactions can induce epigenetic changes in the host directly, as well as indirectly through secreted factors. Previously, uropathogenic Escherichia coli (UPEC) was shown to increase DNA methyltransferase activity and expression, which was associated with methylation-dependent alterations in the urothelial expression of CDKN2A. Here, we showed that paracrine factors from infected cells alter expression of another epigenetic writer, EZH2, coordinate with proliferation. Urothelial cells were inoculated with UPEC, UPEC derivatives, or vehicle (mock infection) at low moi, washed, then maintained in media with Gentamycin. Urothelial conditioned media (CM) and extracellular vesicles (EV) were isolated after the inoculations and used to treat naïve urothelial cells. EZH2 increased with UPEC infection, inoculation-induced CM, and inoculation-induced EV vs. parallel stimulation derived from mock-inoculated urothelial cells. We found that infection also increased proliferation at one day post-infection, which was blocked by the EZH2 inhibitor UNC1999. Inhibition of demethylation at H3K27me3 had the opposite effect and augmented proliferation. CONCLUSION: Uropathogen-induced paracrine factors act epigenetically by altering expression of EZH2, which plays a key role in early host cell proliferative responses to infection.

Bacterial Skin Infections.

Skin and soft tissue infections account for 0.5% of outpatient visits to primary care. Skin and soft tissue infections can usually be managed in an outpatient setting. However, there are certain circumstances as discussed in this article that require more urgent care or inpatient management. Primary care providers should be able to diagnose, manage, and provide appropriate follow-up care for these frequently seen skin infections. This article provides family physicians with a comprehensive review of the assessment and management of common bacterial skin infections.

Mode of action classification of chemicals using multi-concentration time-dependent cellular response profiles.

In this paper, we present a new statistical pattern recognition method for classifying cytotoxic cellular responses to toxic agents. The advantage of the proposed method is to quickly assess the toxicity level of an unclassified toxic agent on human health by bringing cytotoxic cellular responses with similar patterns (mode of action, MoOA) into the same class. The proposed method is a model-based hierarchical classification approach incorporating principal component analysis (PCA) and functional data analysis (FDA). The cytotoxic cell responses are represented by multi-concentration time-dependent cellular response profiles (TCRPs) which are dynamically recorded by using the xCELLigence real-time cell analysis high-throughput (RTCA HT) system. The classification results obtained using our algorithm show satisfactory discrimination and are validated using biological facts by examining common chemical mechanisms of actions with treatment on human hepatocellular carcinoma cells (HepG2).

Rhabdomyosarcoma-associated renal cell carcinoma: a link with constitutional Tp53 mutation.

The 2004 World Health Organization classification includes the new entity "neuroblastoma-associated renal cell carcinoma." The pathogenetic link between these entities is unknown as yet. The patient reported herein developed renal cell carcinoma after anaplastic embryonal rhabdomyosarcoma, a previously unknown association. The 2nd malignancy developed very soon after the 1st one, prompting concern for inherent cancer predisposition rather than a therapy-induced 2nd malignancy. A variety of features raised suspicion for Tp53 mutation, and indeed a pathogenic germline Tp53 mutation was identified in this child, despite a negative family history for Li-Fraumeni syndrome. Consideration of underlying predisposition is advocated in the context of rapid evolution of 2nd childhood malignancy.

Clathrate formation from octaazaphthalocyanines possessing bulky phenoxyl substituents: a new cubic crystal containing solvent-filled, nanoscale voids.

The synthesis of octaazaphthalocyanine (AzaPc) derivatives, with bulky phenoxyl substituents placed at eight peripheral positions and containing either H(+), Ni(2+) or Zn(2+) ions in their central cavity, is described. The required precursors, derivatives of pyrazine-2,3-dicarbonitrile, were prepared using a nucleophilic aromatic substitution reaction between 2,6-diisopropylphenol or 2,6-diphenylphenol and 5,6-dichloropyrazine-2,3-dicarbonitrile. Analysis of the resulting AzaPcs by UV/Visible and (1)H NMR spectroscopy confirms that steric isolation of the AzaPc cores was enforced both in solution and in the solid state. X-ray diffraction studies of single crystals of the AzaPcs reveal that solvent inclusion takes place in each case. Of particular significance is the finding that the zinc derivative of 2,3,9,10,16,17,23,24-octa-(2,6-diisopropylphenoxy)octaazaphthalocyanine provides nanoporous cubic crystals, containing massive (8 nm(3)) solvent-filled voids, similar to those of the analogous phthalocyanine derivative. Exchange of the included solvent within the voids can be readily achieved by using a number of alternative solvents including water. Based on the observed loading of included water, the internal volume of this nanoporous cubic crystal appears to be more hydrophilic than its phthalocyanine counterpart.

Childhood primary parotid non-Hodgkin's lymphoma with direct intracranial extension: a case report.

Childhood primary parotid non-Hodgkin's lymphoma (NHL) is a rare but well-recognized entity in the literature. Perineural extension of masses between the head and neck and cranium, although rare, has also been well documented. We report the first documented case, to our knowledge, of a left-sided primary parotid NHL in a child with direct intracranial extension through the foramen rotundum. The mass arose in a 1 1/2-month period. Following evaluation by computed tomography and magnetic resonance imaging, diagnostic procedures (first, fine-needle aspiration and, subsequently, an open biopsy) were undertaken. We discuss the case report and briefly review childhood NHL and perineural metastasis.

Primary perineal alveolar rhabdomyosarcoma metastatic to an extraocular muscle.

A 17-year-old boy diagnosed with an alveolar rhabdomyosarcoma involving the perineum and with extensive lymphadenopathy was treated with chemotherapy yet developed metastases to the head and neck 6 months into therapy. Ten months after initial diagnosis, while receiving salvage chemotherapy and radiotherapy, he returned with pain on movement of his left eye, proptosis, and ptosis of the left upper eyelid. Computed tomography (CT) revealed a mass within the left lateral rectus muscle that biopsy confirmed to be metastatic alveolar rhabdomyosarcoma. Despite continued chemotherapy and radiotherapy, he ultimately died of the disease. Alveolar rhabdomyosarcoma from distant sites rarely metastasizes to the extraocular muscles. However, our case shows that alveolar rhabdomyosarcoma may metastasize to the orbit and involve a single muscle.