Re-Analyses of 8 Historical Trials in Cardiovascular Medicine Assessing Multimorbidity Burden and Its Association with Treatment Response.

OBJECTIVE: The purpose of this study was to examine the multimorbidity burden of clinical trial participants and assess its association with treatment response. METHODS: We conducted a reanalysis of patient level data. There were 29,954 participants from 8 clinical trials containing 11 comparisons between an intervention and control condition. Patients were classified by Charlson Comorbidity Index (CCI) score. The primary outcomes were the primary study endpoints as originally specified for each trial. A Cox model that included the CCI score groups, the randomized group, and their interaction, was used to compare the primary outcome between randomized groups. The interaction term between randomized group and comorbidity index allowed the treatment effect to differ by level of comorbidity index and comprised the primary effect of interest. Hazard ratios and risk differences were reported for all comparisons. RESULTS: The mean CCI scores of trial populations ranged from 2.1 to 3.9 points, and the percentage of patients with scores ≥5 from 3% to 39%. Tests of interaction terms in models yielded P values ≤ .10 for 4/11 comparisons and ≤ .05 for 2/11 comparisons. In 3 additional comparisons, potentially important treatment variation on an absolute scale was observed despite interaction tests with P values > .10 on the relative scale. CONCLUSIONS: These trials were mainly composed of patient populations with CCI scores ≤4. Despite this, biologically plausible treatment interactions were commonly suggested. These results are hypothesis generating; confirmation of results would require larger studies or studies targeted specifically toward patients with higher levels of multimorbidity.

Two versus three doses of COVID-19 vaccine and post-vaccination COVID-19 infection in hemodialysis patients.

Background and aim: Patients with chronic kidney disease including those undergoing hemodialysis (HD) constitute a particularly challenging group regarding COVID-19 vaccination. The present study aimed to compare the rate of reinfection after two and three doses of Sinopharm COVID-19 vaccine in HD patients. Patients and methods: The study included 80 HD patients who received three doses of Sinopharm COVID-19 vaccine. In addition, there were another 80 patients who received only two doses of the vaccine. Patients in the latter group were selected based on propensity matching score with 1:1 ratio. Patients were monitored for post-vaccination COVID-19 infection using PCR examination of nasopharyngeal swabs. Patients were also monitored for post-vaccination complications including general complaints (headache, fever, fatigue), injection site complaints (arm pain, swelling, itching, rash), musculoskeletal complaints (muscle spasm or pain, joint pain) and others. All patients were followed for six months. Results: The present study included 80 patients submitted to COVID-19 vaccination with two doses of Sinopharm vaccine (GI) and other 80 patients who received three doses of the same vaccine (GII). At the end of follow up, 11 patients (13.8 %) in GI caught COVID-19 infection. In contrast, no patient in GII had infection (P<0.001). Comparison between patients who had COVID-19 infection and those without infection revealed that the former subgroup had significantly lower BMI (23.3 ± 2.3 versus 27.5 ± 8.1 Kg/m2), higher frequency of associated Hepatitis C (HCV) infection (54.6 % versus 2.9 %, P<0.001) and higher serum ferritin levels [median (IQR): 1101.0 (836.0-1564.0) versus 675.0 (467.0-767.7) ng/mL, P=0.01]. Binary logistic regression analysis identified high serum ferritin levels [OR (95% CI): 0.014 (0.001-0.15), P<0.001] and associated HCV infection [OR (95% CI): 0.99 (0.98-1.01), P=0.02] as significant predictors of post-vaccination COVID-19 infection in multivariate analysis. Conclusions: A three dose regime of Sinopharm COVID-19 vaccine associated with significantly lower rate of reinfection COVID-19 infection in HD patients. Infected patients had significantly lower BMI, higher frequency of HCV and higher ferritin levels.

HeartWare Left Ventricular Assist Device Exercise Hemodynamics With Speed Adjustment Based on Left Ventricular Filling Pressures.

Functional capacity remains limited in heart failure patients with left ventricular assist devices (LVADs) due to fixed pump speed and inability to offload the left ventricle adequately. We hypothesized that manually adjusting LVAD speed during exercise based on pulmonary capillary wedge pressures would increase total cardiac output and maximal oxygen consumption. Two participants with a HeartWare LVAD underwent an invasive ramp study at rest followed by an invasive cardiopulmonary stress test exercising in two randomized phases: fixed speed and adjusted speed. In the latter phase, speed was adjusted every 1 minute during exercise at ±20 rpm/1 mm Hg change from baseline pulmonary capillary wedge pressure. There was no difference in maximal oxygen consumption between the two phases, with a modest increase in total cardiac output during speed adjustment. Filling pressures were initially controlled during speed adjustment until speed was capped at 4,000 rpm, at which point filling pressures increased. Blood pressure was variable. The pressure across the head of the pump (ΔP) was higher with speed adjustment. Contrary to our hypothesis, LVAD speed adjustment during exercise did not improve total cardiac output and functional capacity. This variable response may be attributed to the native cardiac reserve and baroreceptor response; however, additional studies are needed.

Differential expression of serum miR-486 and miR-25 in ulcerative colitis and Crohn's disease: Correlations with disease activity, extent, and location.

Novel reliable biomarkers of inflammatory bowel disease (IBD) are clinically imperative due to potential limitations of endoscopic techniques. MicroRNAs (miRNAs) have emerged as non-invasive biomarkers of IBD; however, the full disease-specific miRNAs signature for IBD subtypes remains elusive. We evaluated the diagnostic role of circulating miR-486 and miR-25 in IBD patients and their potential ability to discriminate IBD subtypes; ulcerative colitis (UC) and Crohn's disease (CD). Sixty UC patients, 60 CD patients, and 60 healthy controls were recruited. Serum miRNA expression was determined using RT-qPCR. Bioinformatics was employed for target gene and protein-protein interaction (PPI) network analyses. Serum miR-486 was upregulated in CD patients, but didn't change in UC patients compared to controls. Conversely, serum miR-25 was decreased in both CD and UC patients compared to controls. Only miR-486 was differentially expressed between UC and CD patients. Receiver-operating characteristic analysis revealed that serum miR-486 was superior in CD diagnosis (AUC=0.945) and significantly distinguished CD and UC patients, whereas miR-25 showed discriminative potential for both UC and CD from controls. In the multivariate logistic analysis only miR-486 was associated with the risk of CD diagnosis. Serum miR-486 was correlated with CD activity index and location of disease in CD patients, whereas miR-25 was correlated with the type/extent of UC. PPI network analysis revealed common target genes and signaling pathways for both miRNAs. Conclusively, serum miR-486 and miR-25 might serve as new biomarkers of IBD, with serum miR-486 could be employed in risk stratification of IBD subtypes and has the ground for clinical utility in CD diagnosis, whereas miR-25 has potential for UC and CD diagnosis.

Knee MRI biomarkers associated with structural, functional and symptomatic changes at least a year from ACL injury - A systematic review.

Introduction: Osteoarthritis (OA) results from various aetiologies, including joint morphology, biomechanics, inflammation, and injury. The latter is implicated in post-traumatic OA, which offers a paradigm to identify potential biomarkers enabling early identification and intervention. This review aims to describe imaging features associated with structural changes or symptoms at least one year following injury. Methodology: A systematic review was conducted using PRISMA guidance, prospectively registered on PROSPERO (CRD42022371838). Three independent reviewers screened titles and abstracts, followed by full-texts, performed data extraction, and risk of bias assessments (Newcastle-Ottawa Scale). Inclusion criteria included imaging studies involving human participants aged 18-45 who had sustained a significant knee injury at least a year previously. A narrative synthesis was performed using synthesis without meta-analysis methodology. Results: Six electronic databases and conference proceedings were searched, identifying 11 studies involving 776 participants. All studies included participants suffering an anterior cruciate ligament (ACL) injury and utilised MRI. Different, and not directly comparable, techniques were used. MRI features could be broadly divided into structural, including joint position and morphology, and compositional. Promising biomarkers for diagnosing and predicting osteoarthritis include T1rho and T2 relaxation time techniques, bone morphology changes and radiomic modelling. Discussion: As early as 12 months after injury, differences in tibia position, bone morphology, presence of effusion and synovitis, and cartilage/subchondral bone composition can be detected, some of which are linked with worse patient-reported or radiological progression. Standardisation, including MR strength, position, sequence, scoring and comparators, is required to utilise clinical and research OA imaging biomarkers fully.

Cognitive enhancing effects of pazopanib in D­galactose/ovariectomized Alzheimer's rat model: insights into the role of RIPK1/RIPK3/MLKL necroptosis signaling pathway.

Necroptosis, a programmed form of necrotic cell death carried out by receptor-interacting serine/threonine protein kinase 1 (RIPK1) and RIPK3, has been found to be implicated in the pathogenesis of Alzheimer's disease (AD). An FDA-approved anti-cancer drug, pazopanib, is reported to possess potent inhibitory effect against necroptosis via interfering with RIPK1. So far, there are no existing data on the influence of pazopanib on necroptotic pathway in AD. Thus, this study was designed to explore the impact of pazopanib on cognitive impairment provoked by ovariectomy (OVX) together with D-galactose (D-Gal) administration in rats and to scrutinize the putative signaling pathways underlying pazopanib-induced effects. Animals were allocated into four groups; the first and second groups were exposed to sham operation and administered normal saline and pazopanib (5 mg/kg/day, i.p.), respectively, for 6 weeks, while the third and fourth groups underwent OVX then were injected with D-Gal (150 mg/kg/day, i.p.); concomitantly with pazopanib in the fourth group for 6 weeks. Pazopanib ameliorated cognitive deficits as manifested by improved performance in the Morris water maze besides reversing the histological abnormalities. Pazopanib produced a significant decline in p-Tau and amyloid beta (Aß) plaques. The neuroprotective effect of pazopanib was revealed by hampering neuroinflammation, mitigating neuronal death and suppressing RIPK1/RIPK3/MLKL necroptosis signaling pathway. Accordingly, hindering neuroinflammation and the necroptotic RIPK1/RIPK3/MLKL pathway could contribute to the neuroprotective effect of pazopanib in D-Gal/OVX rat model. Therefore, this study reveals pazopanib as a valuable therapeutic agent in AD that warrants future inspection to provide further data regarding its neuroprotective effect.

Accuracy of Rapid Emergency Medicine Score and Sequential Organ Failure Assessment Score in predicting acute paraphenylenediamine poisoning adverse outcomes.

Paraphenylenediamine (PPD) is a commonly used xenobiotic in hair dying, causing deleterious outcomes in acute poisoning. Although many epidemiological studies and case reports explained their clinical presentations and fatal consequences, no studies have evaluated the early determinants of adverse outcomes. Therefore, the present study aimed to assess the initial predictors of acute PPD poisoning adverse outcomes, focusing on the discriminatory accuracy of the Rapid Emergency Medicine Score (REMS) and Sequential Organ Failure Assessment (SOFA) score. A retrospective cohort study included all acute PPD-poisoned patients admitted to three Egyptian emergency hospitals from January 2020 to January 2022. Data was gathered on admission, including demographics, toxicological, clinical, scoring systems, and laboratory investigations. Patients were categorized according to their outcomes (mortality and complications). Ninety-seven patients with acute PPD poisoning were included, with a median age of 23 years, female predominance (60.8%), and suicidal intention (95.9%). Out of all patients, 25.77% died, and 43.29% had complicated outcomes. Respiratory failure was the primary cause of fatalities (10.30%), while acute renal failure (38.14%) was a chief cause of complications. The delay time till hospitalization, abnormal electrocardiogram, initial creatine phosphokinase, bicarbonate level, REMS, and SOFA scores were the significant determinants for adverse outcomes. The REMS exhibited the highest odds ratio (OR = 1.91 [95% confidence interval (CI): 1.41-2.60], p < 0.001) and had the best discriminatory power with the area under the curve (AUC) = 0.918 and overall accuracy of 91.8% in predicting mortality. However, the SOFA score had the highest odds ratio (OR = 4.97 [95% CI: 1.16-21.21], p = 0.001) and only yielded a significant prediction for complicated sequels with AUC = 0.913 and overall accuracy of 84.7%. The REMS is a simple clinical score that accurately predicts mortality, whereas the SOFA score is more practicable for anticipating complications in acute PPD-poisoned patients.

Different Aspects of Diabetes in Hospitalized Patients with COVID-19.

Background: The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) causes COVID-19, a recent infectious disease that aggravates the underlying pathophysiology of hyperglycemia in diabetic individuals. This study aimed to detect how diabetes mellitus (DM) affected COVID-19 patients' morbidity and mortality, and the incidence of neonset DM. Patients and Methods: The present study was a cross-sectional study done at Aswan Isolation Hospitals, Egypt. It comprised 200 individuals who had been tested positive for COVID-19. They were divided into two groups: group 1 (pre-existing diabetes = 143 patients) and group 2 (new-onset diabetes = 57 patients), and all patients were subjected to general examinations, hospital stay duration, and investigations, such as (complete blood count, urea, creatinine, HBA1c, fasting, postprandial, and random blood sugar, D-Dimer, ferritin, C-reactive protein, PCR for SARS COV-2 RNA, and CT chest. Results: The current study consisted of 94 males and 106 females. According to disease severity, they were 96 (48.0%) critical cases, 57 (28.5%) severe cases, and 47 (23.5%) non-severe cases. The incidence of new-onset DM in COVID-19 patients was 28.5% (57 new cases), with a mortality rate of 42.0% (84 cases). Regarding glycemic control, we found a significant difference in fasting blood sugar (FBS) between the two groups, with a significant increase of FBS in the dead group than in the survived group. We also found a significant age difference in critical than in severe and non-severe groups, with a high mortality rate in older patients. Inflammatory markers, such as ferritin, CRP, and D-dimer, were higher in critical than in severe and non-severe groups. Conclusion: The prevalence of new-onset DM is significant among hospitalized COVID-19 patients. Older patients were more prone to disease severity with high mortality rate. Inflammatory markers such as CRP and ferritin were significantly related to the COVID-19 severity and outcome.

Dual PI3K/Akt Inhibitors Bearing Coumarin-Thiazolidine Pharmacophores as Potential Apoptosis Inducers in MCF-7 Cells.

Breast cancer is the most common malignancy worldwide; therefore, the development of new anticancer agents is essential for improved tumor control. By adopting the pharmacophore hybridization approach, two series of 7-hydroxyl-4-methylcoumarin hybridized with thiosemicarbazone (V-VI) and thiazolidin-4-one moieties (VII-VIII) were prepared. The in vitro anticancer activity was assessed against MCF-7 cells adopting the MTT assay. Nine compounds showed significant cytotoxicity. The most promising compound, VIIb, induced remarkable cytotoxicity (IC50 of 1.03 + 0.05 µM). Further investigations were conducted to explore its pro-apoptotic activity demonstrating S-phase cell cycle arrest. Apoptosis rates following VIIb treatment revealed a 5-fold and 100-fold increase in early and late apoptotic cells, correspondingly. Moreover, our results showed caspase-9 dependent apoptosis induction as manifested by an 8-fold increase in caspase-9 level following VIIb treatment. Mechanistically, VIIb was found to target the PI3K-α/Akt-1 axis, as evidenced by enzyme inhibition assay results reporting significant inhibition of examined enzymes. These findings were confirmed by Western blot results indicating the ability of VIIb to repress levels of Cyclin D1, p-PI3K, and p-Akt. Furthermore, docking studies showed that VIIb has a binding affinity with the PI3K binding site higher than the original ligands X6K. Our results suggest that VIIb has pharmacological potential as a promising anti-cancer compound by the inhibition of the PI3K/Akt axis.

Pyrimidine-5-carbonitrile based potential anticancer agents as apoptosis inducers through PI3K/AKT axis inhibition in leukaemia K562.

A novel series of 4-(4-Methoxyphenyl)-2-(methylthio)pyrimidine-5-carbonitrile was developed linked to an aromatic moiety via N-containing bridge and then evaluated for their cytotoxic activity against MCF-7 and K562 cell lines. Seven compounds exhibited the highest activity against both cell lines where compounds 4d and 7f were the most active against K562 cell line. Exploring their molecular mechanisms by enzyme inhibition assay on PI3Kδ/γ and AKT-1 showed that compound 7f was promising more than 4d with IC50 = 6.99 ± 0.36, 4.01 ± 0.55, and 3.36 ± 0.17 uM, respectively. Also, flowcytometric analysis revealed that 7f caused cell cycle arrest at S-phase followed by caspase 3 dependent apoptosis induction. Mechanistically, compound 7f proved to modulate the expression of PI3K, p-PI3K, AKT, p-AKT, Cyclin D1, and NFΚß. Furthermore, in-vivo toxicity study indicated good safety profile for 7f. These findings suggest that the trimethoxy derivative 7f has strong potential as a multi-acting inhibitor on PI3K/AKT axis targeting breast cancer and leukaemia.

Antiproliferatives and Transplantation.

Antiproliferative agents include Mycophenolic acid and Azathioprine (which is less commonly used unless in certain conditions). They were initially identified for use in autoimmune and cancer research due to their role in disruption of cellular replication. They have now become the cornerstone of antirejection maintenance therapy in solid organ transplant. In this chapter we will describe the major times that lead to discovery, mechanisms of action, side effects, use during pregnancy and the major clinical trials.

Are SPECT MPI measures of dyssynchrony dyssynchronous?

BACKGROUND: Assessment of left ventricular mechanical dyssynchrony (LVMD) from gated SPECT myocardial perfusion imaging (MPI) aims to aid selection of patients for cardiac resynchronization therapy (CRT), using either the standard deviation of left ventricular phase (PSD) ≥ 43° or phase histogram bandwidth (HBW) of > 38° and > 30.6° in males and females, respectively. We observed dyssynchrony parameters might be affected by test type and alignment. METHODS: We reviewed 242 patients who underwent gated SPECT MPI with use of the Emory Cardiac Toolbox comparing PSD and HBW at rest and stress for Pearson correlation, and substitutability with Bland-Altman analysis. RESULTS: There is statistically significant difference in the mean PSD and HBW during rest vs stress (33.4 ± 17.4° vs 20.7 ± 13.5° and 97.7 ± 59.6° vs 59.4 ± 45.4°, respectively, P < 0.001). Proper valve plane alignment rendered smaller values (i.e., less dyssynchrony) in both phase SD and HBW (16.8 ± 13.5) vs (22.2 ± 14.7) (P = 0.011), and (47.0 ± 38.2) vs (60.7 ± 48.0) (P = 0.023), respectively. CONCLUSION: Proper alignment and test type, particularly low-dose rest vs high-dose stress, should be considered when assessing LVMD using SPECT MPI.

Infection and mortality of healthcare workers worldwide from COVID-19: a systematic review.

OBJECTIVES: To estimate COVID-19 infections and deaths in healthcare workers (HCWs) from a global perspective during the early phases of the pandemic. DESIGN: Systematic review. METHODS: Two parallel searches of academic bibliographic databases and grey literature were undertaken until 8 May 2020. Governments were also contacted for further information where possible. There were no restrictions on language, information sources used, publication status and types of sources of evidence. The AACODS checklist or the National Institutes of Health study quality assessment tools were used to appraise each source of evidence. OUTCOME MEASURES: Publication characteristics, country-specific data points, COVID-19-specific data, demographics of affected HCWs and public health measures employed. RESULTS: A total of 152 888 infections and 1413 deaths were reported. Infections were mainly in women (71.6%, n=14 058) and nurses (38.6%, n=10 706), but deaths were mainly in men (70.8%, n=550) and doctors (51.4%, n=525). Limited data suggested that general practitioners and mental health nurses were the highest risk specialities for deaths. There were 37.2 deaths reported per 100 infections for HCWs aged over 70 years. Europe had the highest absolute numbers of reported infections (119 628) and deaths (712), but the Eastern Mediterranean region had the highest number of reported deaths per 100 infections (5.7). CONCLUSIONS: COVID-19 infections and deaths among HCWs follow that of the general population around the world. The reasons for gender and specialty differences require further exploration, as do the low rates reported in Africa and India. Although physicians working in certain specialities may be considered high risk due to exposure to oronasal secretions, the risk to other specialities must not be underestimated. Elderly HCWs may require assigning to less risky settings such as telemedicine or administrative positions. Our pragmatic approach provides general trends, and highlights the need for universal guidelines for testing and reporting of infections in HCWs.

Cardiovascular System Affection and Its Relation to First-Year Mortality in Patients Initiating Maintenance Hemodialysis.

BACKGROUND: The incidence of end-stage renal disease (ESRD) has increased by 30-40% in the last decade. These patients have a higher mortality rate of 3-8 times compared to the general population. In the present study, we aimed to detect cardiovascular complications and their relation to the first-year mortality rate in patients on hemodialysis in Aswan University Hospital, upper Egypt. PATIENTS AND METHODS: Our study was a cross-sectional study which was done at the hemodialysis unit in Aswan University Hospital from May 2016 to May 2018. The study included 100 patients with ESRD on regular hemodialysis (first year on programmed hemodialysis). All patients were subjected to full clinical examination and laboratory studies includngd complete blood count (CBC), kidney function tests, serum calcium and phosphorus level, parathormone (PTH) hormone, serum albumin level, C-reactive protein (CRP), echocardiography and electrocardiogram (ECG), and lateral abdominal x-ray for detection of aortic calcification. . RESULTS: The present study included 47 males and 53 females, with a mean age of 50.6 ±13.89 years. The main risk factors for patients with ESRD were hypertension (48%) followed by diabetic nephropathy (36%), glomerulonephritis (15%), idiopathic etiology (11%), obstructive uropathy (8%), lupus nephritis (6%), polycystic kidney disease (4%) and cardio renal syndrome (1%). Twenty-seven deaths have been noted during the first year of dialysis treatment. The leading causes of death were cardio-vascular events (66, 67%), infection (22, 22%) and malignancy (11, 11%), The most common cardiovascular events were myocardial infarction (27.8%), sudden cardiac death (SCD) (27.8%) and heart failure (22.2%). CONCLUSION: In conclusion, our study showed that the main risk factors for ESRD patients in Aswan University Hospital are hypertensive nephrosclerosis, diabetic nephropathy, glomerulonephritis and idiopathic etiology, and the main causes of first-year mortality were cardiovascular events followed by infection and malignancy.

Golgi Protein 73 versus Alpha-Fetoprotein as a New Biomarker in Early Diagnosis of Hepatocellular Carcinoma.

BACKGROUND: Screening of early hepatocellular carcinoma (HCC) diagnosis is the greatest challenge for hepatologists. Alpha-fetoprotein (AFP) is the most common non-invasive biomarker used in HCC diagnosis. OBJECTIVES AND AIMS: To make a comparison between the new biomarker Golgi protein 73 (GP73) versus the standard biomarker AFP in the diagnosis of HCC. METHODS: Our study was a case-control study, and 60 patients were included in the study. They were divided into two groups: 1) HCC patients with either chronic HBV or HCV infection (n=30); and 2) non-HCC patients with HBV or HCV infection who had either chronic hepatitis or liver cirrhosis (n=30). In addition, 30 healthy volunteers were included as a control group. Patients were subjected to liver function tests, kidney function tests, serum Golgi protein 73 and AFP levels. Imaging diagnosis of HCC was done by computed tomography (CT) or magnetic resonance imaging (MRI) based on American Association for the Study of Liver Diseases (AASLD) practice guidelines. RESULTS: Statistically significant differences between groups in terms of serum AFP (p<0.001) and GP73 (p<0.001) were found. Non-HCC patients (chronic hepatitis and liver cirrhosis) and HCC patients had significantly higher AFP and GP73 than the control group. In addition, patients with HCC had significantly higher AFP and GP73 than chronic hepatitis and cirrhotic patients. GP73 had higher diagnostic performance than AFP. At a cut-off value of ≥8.4 ng/mL, GP73 yielded a sensitivity of 86.7% and specificity of 89% for the discrimination between HCC and normal populations. Similarly, at a cut-off value of ≥8.45 ng/mL, GP73 yielded a sensitivity of 83.3% and specificity of 84% for the discrimination between HCC patients and non-HCC patients. On the other hand, AFP at a cut-off value of ≥2.4 ng/mL yielded a sensitivity of 75.4% and specificity of 90% for the discrimination between HCC and normal populations; and at a cut-off value of ≥20.85 ng/mL, AFP yielded a sensitivity of 72.2% and specificity of 86.2% for the discrimination between HCC and non-HCC patients. CONCLUSION: Golgi protein 73 is a promising and accurate biomarker for early detection of HCC.

Remote Physiologic Monitoring for Heart Failure.

PURPOSE OF REVIEW: This review will describe the process of remote monitoring in the treatment of heart failure and the clinical trials for different modalities of data collection. RECENT FINDINGS: Small studies monitoring weights, sometimes with other parameters, suggested a significant outcome benefit in meta-analysis. However, this has not been seen in larger studies. Clinical trials of remote monitoring using hemodynamic parameters seems to lead to improved outcomes, with more studies underway. Recently, multi-parameter methods with wearable or implantable devices have shown promise in detecting heart failure. The impact on clinical outcomes is being assessed. When using parameters such as daily weights, remote monitoring for heart failure has not been demonstrated to be broadly beneficial, while remote monitoring of hemodynamic parameters to guide heart failure therapy has met with initial success. Methods of combining multiple physiologic measurements appear to accurately detect worsening heart failure, and clinical trials are underway to assess the impact.

The expression of microRNA 146a in patients with ischemic stroke: an observational study.

AIM: We conducted the present prospective study to assess the level of microRNA (miRNA) 146a in patients with ischemic stroke and its correlation with patients' characteristics. METHODS: We conducted an observational study that included adult patients (≥18 years old) who presented within 24 hrs after the onset of the symptoms of acute ischemic stroke. In addition, age- and sex-matched healthy volunteers were included as control group. The primary outcome in the present study was the difference in miRNA 146a expression between patients with ischemic stroke and control group participants. The expression of miRNA 146a was measured using quantitative real-time PCR. Quantitative real-time PCR amplification and analysis were performed using Rotor-Gene Q thermal cycler. RESULTS: The present study included 44 patients with ischemic stroke and 22 matched controls. Regarding the primary outcome of the present study, the median expression of miRNA 146a in patients with ischemic stroke was -1.98 fold (IQR -27.1-3.9) compared to 1.75 fold (IQR -2.25-5.27) in control group (P<0.001). However, the subgroup analysis showed that the expression of miRNA 146a was significantly downregulated in comatosed patients only (P<0.001). The expression of miRNA 146a correlated negatively with Glasgow Coma Scale score in comatose patients (r=-0.352, P=0.022). CONCLUSION: In conclusion, the expression of miRNA 146a is significantly downregulated in ischemic stroke patients. Further studies are needed to assess its diagnostic utility and therapeutic potentials.

miR-26a Potentially Contributes to the Regulation of Fatty Acid and Sterol Metabolism In Vitro Human HepG2 Cell Model of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a metabolic-related disorder ranging from steatosis to steatohepatitis, which may progress to cirrhosis and hepatocellular carcinoma (HCC). This study aimed at assessing the regulatory and protective role of miR-26a on lipid metabolism and progression of NAFLD in human HepG2 cells loaded with free fatty acids (FFA). Lentivirus expressing miR-26a or negative control miR was used to transduce HepG2 cells and to establish stable cell lines. Gain or loss of function using an miR-26a inhibitor was used to compare triglyceride content (TG), total cholesterol level (CL), total antioxidant capacity (TAC), malondialdehyde (MDA) and the level of apoptosis. In addition, quantitative reverse transcription polymerase chain reaction (qPCR) was used to assess the mRNA levels of lipogenesis, TG synthesis, storage genes, inflammatory and fibrogenic markers, and autophagic besides endoplasmic reticulum (ER) stress markers after gaining or losing the function of miR-26a. miR-26a levels decreased in response to FFA in human HepG2 cells. After the establishment of a stable cell line, the upregulation of miR-26a resulted in the downregulation of TG, CL, and MDA levels, through regulating mRNA levels of genes involved in lipid homeostasis, ER stress marker, inflammatory and fibrogenic markers. Nevertheless, there was a marked increment in the mRNA expression of autophagic marker genes. Moreover, miR-26a overexpression protects the cells from apoptosis, whereas inhibition of miR-26a, using an anti-miR-26a oligonucleotide, decreased the expression of miR-26a which potentially contributes to altered lipid metabolism in HepG2 cells loaded with FFA. In conclusion, these findings suggested that miR-26a has a crucial role in regulating fatty acid and cholesterol homeostasis in HepG2 cells, along with the offered protection against the progression of NAFLD in vitro. Hence, miRNAs could receive growing attention as useful noninvasive diagnostic markers to follow the progression of NAFLD and to identify novel therapeutic targets.

Negative axillary ultrasonography with biopsy may predict non-involvement of the non-sentinel lymph nodes in operable breast cancer patients.

AIM: To evaluate whether axillary ultrasound in combination with a biopsy (AUS +/- Bx) can predict the involvement of the non-sentinel lymph nodes (NSLN). METHODS: A review of all operable breast cancer patients who underwent AUS +/- Bx at our tertiary care center from January 2010 to April 2011 was performed. All patients underwent AUS as part of their pre-operative evaluation. If the AUS was suspicious, a fine-needle aspiration or core-needle biopsy was performed. RESULTS: Of 88 patients included in our final analysis, 20 (23%) had positive AUS + Bx and underwent axillary lymph node dissection (ALND) at time of definitive surgery. In all, 68 of the 88 patients (77.3%) had negative AUS +/- Bx and underwent sentinel lymph node (SLN) Bx at the time of definitive surgery. If the SLN Bx was negative, no further axillary surgery was performed and the NSLN were assumed to be negative. If the SLN Bx was positive, ALND was performed. Of the 68 patients, 62 (91%) had a negative NSLN. Patients with positive AUS + Bx carry a relative risk of 2.02 (P < 0.00002) of having positive NSLN. CONCLUSION: In operable breast cancer patients, a negative AUS+/- Bx may be a predictor of non-involvement of the NSLN.

Racial disparities in left main stenting: insights from a real world inner city population.

BACKGROUND: Left main coronary artery (LMCA) disease is associated with significant cardiovascular mortality. The data on patient characteristics' predicting outcomes after LMCA revascularization is sparse. METHODS: A retrospective study of 227 patients with LMCA disease documented on coronary angiography from March 2000 to December 2008. Data included demographic variables, co-morbidities, cardiac function, and medications. Race was self-identified. The study outcome was a composite end-point including myocardial infarction (MI) and all-cause mortality. Cox proportional hazard analysis was performed to study the effect of various patient attributes including race and gender on the composite end-point. RESULTS: Baseline characteristics were specifically compared between individuals who had the study outcome versus those who did not. Mean age was higher in the group with study outcomes when compared to the group without any outcomes (64.3 ± 11.8 years versus 59.2 ± 13.6 years; p = 0.013). After the final multivariate regression analysis, only African American (AA) race and age were found to be independent predictors of adverse cardiac outcome at the end of the first year (race-hazard ratio (HR) 3.82, 95% confidence interval (CI) 1.38-10.62, p = 0.010; age-HR 1.08, 95% CI 1.04-1.13, p < 0.001) and at the end of the study (race-HR 2.71, 95% CI 1.44-5.10, p = 0.002; age-HR 1.03, 95% CI 1.01-1.08, p = 0.017). CONCLUSION: In our study of patients with unprotected LMCA disease, AA race, and age were significantly predictive of poor prognosis following revascularization, while gender had no predictive value in prognosticating cardiovascular mortality.