Beyond Quadruple Therapy and Current Therapeutic Strategies in Heart Failure with Reduced Ejection Fraction: Medical Therapies with Potential to Become Part of the Therapeutic Armamentarium.

Heart failure with reduced ejection fraction (HFrEF) is a complex clinical syndrome with significant morbidity and mortality and seems to be responsible for approximately 50% of heart failure cases and hospitalizations worldwide. First-line treatments of patients with HFrEF, according to the ESC and AHA guidelines, include ß-blockers, angiotensin receptor/neprilysin inhibitors, sodium-glucose cotransporter 2 inhibitors, and mineralocorticoid receptor antagonists. This quadruple therapy should be initiated during hospital stay and uptitrated to maximum doses within 6 weeks after discharge according to large multicenter controlled trials. Quadruple therapy improves survival by approximately 8 years for a 55-year-old heart failure patient. Additional therapeutic strategies targeting other signaling pathways such as ivabradine, digoxin, and isosorbide dinitrate and hydralazine combination for African Americans, as well as adjunctive symptomatic therapies, seem to be necessary in the management of HFrEF. Although second-line medications have not achieved improvements in mortality, they seem to decrease heart failure hospitalizations. There are novel medical therapies including vericiguat, omecamtiv mecarbil, genetic and cellular therapies, and mitochondria-targeted therapies. Moreover, mitraclip for significant mitral valve regurgitation, ablation in specific atrial fibrillation cases, omecamtiv mecarbil are options under evaluation in clinical trials. Finally, the HeartMate 3 magnetically levitated centrifugal left ventricular assist device (LVAD) has extended 5-year survival for stage D HF patients who are candidates for an LVAD.

The efficacy of Chinese herbal drugs for adults with angina pectoris: Bayesian network meta-analysis of 331 RCTs involving 36,467 individuals.

ETHNOPHARMACOLOGICAL RELEVANCE: Hundreds of randomized controlled trials (RCT) on Chinese herbal drugs (CHDs) including Shexiang baoxin pill (BXP), compound Danshen dripping pill (DSP), compound Danshen tablet (DST), Suxiao jiuxin pill (JXP), Naoxintong capsule (NXT), Tongxinluo capsule (TXL), and Di'ao xinxuekang capsule (XXK) and conventional chemical drugs, such as isosorbide dinitrate (ISDN), for angina pectoris are available but have not been evaluated by a PRISMA-compliant network meta-analysis (NMA). AIM OF THE STUDY: This study aimed to compare the efficacy of nine anti-anginal drugs through NMA on RCTs. METHODS: RCTs of drug treatment for adult patients with angina pectoris for improvements in symptoms and electrocardiography were retrieved. Odds ratios and 95% credible intervals were computed to measure effect sizes. RCT quality was evaluated with the Cochrane risk of bias tool. Evidence synthesis was performed with Bayesian NMA. Essential analyses including subgroup analysis, sensitivity analysis, meta-regression analysis, publication bias analysis, and ranking analysis were conducted to assess the robustness of efficacies. Evidence strength was assessed with the GRADE approach. RESULTS: A total of 331 RCTs with 36,467 participants were eligible. The overall quality of all included RCTs was low. Overall efficacy estimates from different approaches of evidential synthesis found that BXP, TXL, and DSP were more efficacious than DST and ISDN. Essential analyses indicated consistent efficacy estimates, insignificant publication bias, and corroborative ranking results. The overall GRADE evidence strength was low. CONCLUSION: This comprehensive Bayesian NMA found BXP, TXL, and DSP to be the top three candidates among the seven tested CHDs for treating adults suffering from angina pectoris. However, the quality and the evidence strength of eligible RCTs were low. Further high-quality RCTs with more outcome measures and their NMAs are warranted. REGISTRATION: PROSPERO CRD42014007035.

Discovery of Efficient Hypoxia-Targeted NO Donor Compounds to Alleviate Hypoxia Cardiac Disease.

In order to obtain efficient NO donor drugs to treat hypoxic cardiac disease, a series of hypoxia-targeted NO donor compounds were prepared and screened. Among them, a representative compound H3 was found to selectively release NO under hypoxia with a higher ratio than isosorbide dinitrate (ISDN). In vitro study indicated that H3 had a strong capability of alleviating vascular dilation and reducing myocardial hypoxic injury due to its effective regulation of vascular dilatation and myocardial injury-related proteins in H9c2 cells even at low concentrations. By intraperitoneal injection or intragastric administration, in vivo animal tests revealed that H3 possessed a potent antimyocardial hypoxic injury effect superior to ISDN. These findings suggest that H3 has a better effect on alleviating hypoxic cardiac disease than the conventional drug, owing to its hypoxia-targeted release of NO.

Prevention of Preterm Labor by Isosorbide Dinitrate and Nitroglycerin Patch.

BACKGROUND: Preterm labor is one of the most important causes of hospitalization during pregnancy and can lead to serious complications in neonates. OBJECTIVE: This study aims to compare the effect of transdermal nitroglycerin (TNG) patches and sublingual tablets of Isosorbide dinitrate (ISD) for the prevention of preterm delivery. METHODS: A total of 110 healthy pregnant women aged 18-35 years with a healthy and alive fetus and gestational age between 24-34 weeks who had at least 8 regular uterine contractions per hour were included in this single-blinded clinical trial. After exclusion, the women were randomly divided into TNG (n = 50) and ISD (n = 49) groups. After the first dose of medication (TNG or ISD), patients who developed complications such as hypotension, headache, or both, were also excluded from the study. RESULTS: A total of 58 patients completed the treatment course (29 patients in each group). A significant difference in delayed preterm labor and recovery time was reported between the TNG and ISD groups. CONCLUSION: Complications and the number of contractions were not statistically different in the two groups. We concluded that the TNG patch is more effective than ISD in delaying labor. Both drugs are likely to have a similar incidence of side effects.

Combination Therapy With Nicardipine and Isosorbide Dinitrate to Prevent Spasm in Transradial Percutaneous Coronary Intervention (from the NISTRA Multicenter Double-Blind Randomized Controlled Trial).

Verapamil and nitroglycerin are widely used to prevent radial artery spasm (RAS) during percutaneous cardiovascular procedures. However, these agents are not typically available in most African countries and consequently, isosorbide dinitrate is often the only spasmolytic treatment. Our aim was to compare the efficacy of isosorbide dinitrate alone versus isosorbide dinitrate used together with nicardipine to prevent RAS during transradial coronary procedures. This was a randomized controlled double-blind multicenter trial. Patients (n = 1,523) were randomized to receive either a sole therapy of isosorbide dinitrate (n = 760) or the combination of isosorbide dinitrate and nicardipine (n = 763). Our primary end point was the occurrence of RAS; defined as considerable perceived hindrance of catheter advancement. Our secondary end points were severe RAS; defined as (1) severe arm pain, (2) the need for either morphine or midazolam treatment, and (3) necessity for crossover to the contralateral radial or femoral artery. RAS incidence was reduced with the combination therapy versus isosorbide dinitrate alone (15% vs 25%, p <0.001), with a number needed to treat of 10 patients. There was also a significant reduction in the incidence of the secondary end points with combination therapy (3.6% vs 8.2%, p <0.001), with a number needed to treat of 22 patients. This result was driven by reductions in both femoral crossover (0.5% vs 2.4%, p = 0.003) and the use of morphine or midazolam injections (1.6% vs 3.5%, p = 0.02) with combination therapy. In conclusion, we demonstrated the superiority of the combination therapy of isosorbide dinitrate and nicardipine over isosorbide dinitrate alone in reducing the incidence of RAS.

Synergetic delivery of artesunate and isosorbide 5-mononitrate with reduction-sensitive polymer nanoparticles for ovarian cancer chemotherapy.

Ovarian cancer is a highly fatal gynecologic malignancy worldwide. Chemotherapy remains the primary modality both for primary and maintenance treatments of ovarian cancer. However, the progress in developing chemotherapeutic agents for ovarian cancer has been slow in the past 20 years. Thus, new and effective chemotherapeutic drugs are urgently needed for ovarian cancer treatment. A reduction-responsive synergetic delivery strategy (PSSP@ART-ISMN) with co-delivery of artesunate and isosorbide 5-mononitrate was investigated in this research study. PSSP@ART-ISMN had various effects on tumor cells, such as (i) inducing the production of reactive oxygen species (ROS), which contributes to mitochondrial damage; (ii) providing nitric oxide and ROS for the tumor cells, which further react to generate highly toxic reactive nitrogen species (RNS) and cause DNA damage; and (iii) arresting cell cycle at the G0/G1 phase and inducing apoptosis. PSSP@ART-ISMN also demonstrated excellent antitumor activity with good biocompatibility in vivo. Taken together, the results of this work provide a potential delivery strategy for chemotherapy in ovarian cancer.

Cardiologists' Perspectives on BiDil and the Use of Race in Drug Prescribing.

OBJECTIVES: We explored cardiologists' attitudes and prescribing patterns specific to the use of generic isosorbide dinitrate and hydralazine hydrochloride, and the fixed-dose patented drug, BiDil. BACKGROUND: Since the Food and Drug Administration approved BiDil in 2005 with an indication for self-identified black patients, disagreement about the appropriateness of race-based drugs has intensified and led to calls for providers and researchers to abandon race-based delimitations. This paper reports empirical evidence of cardiologists' views on BiDil's race-based indication and their ongoing inertia with respect to the debate about BiDil. METHODS: We conducted a 2010 cross-sectional online survey of members of the Association of Black Cardiologists. RESULTS: Fifty-nine cardiologists responded to the survey. Most participants (62.7%) prescribed BiDil to their patients. More than 40% of respondents did not prescribe BiDil to any non-African Americans. When considering whether to prescribe BiDil, a patient's race determined by physician assessment was the third most important factor considered by participants. The majority of participants (72.7%) selected symptoms as the most important factor. Most participants (59.2%) perceived race as defining biologically distinct individuals. Respondents prescribed BiDil more often to African American patients than non-African American patients. However, they prescribed the generic components that makeup BiDil to African Americans and non-African American patients similarly. CONCLUSIONS: The survey provides useful findings that, when viewed within the context of ongoing debates about race-based medicine, show little progress toward appropriately utilizing BiDil to maximize health outcomes, yet, might inform the development of practical and effective guidelines concerning the use of race in medicine.

The Efficacy of Nitrates for Bone Health: A Systematic Review and Meta-Analysis of Observational and Randomized Controlled Studies.

Background: Although some studies have found that nitrates were beneficial for bone health, the findings are inconsistent. To assess the efficacy of nitrates for bone health, we conducted a meta-analysis. Methods: PubMed, EMBASE databases, Cochrane Library for relevant articles published before December 2021 were searched. All observational and randomized controlled studies that reporting bone mineral density (BMD), fractures with nitrates use were included. A meta-analysis was performed to calculate risk ratios (RRs) for fractures, change differences for bone mineral density. Results: Four cohort studies and two case-control studies examining the association between nitrates use and fractures were identified. The nitrates use was not associated with any fracture risk (RR = 0.97; 95% CI, 0.94-1.01; I2 = 31.5%) and hip fracture (RR = 0.88; 95% CI, 0.76-1.02; I2 = 74.5%). Subgroup analyses revealed no differences in fracture risk, whereas two cohort studies revealed a reduced risk of hip fracture (RR = 0.71, 95% CI, 0.58-0.86, I2 = 0.0%). There were no statistically significant differences in BMD percent changes at lumbar spine (WMD = -0.07, 95% CI,-0.78-0.65; I2 = 0.0%), total hip (WMD = -0.42, 95% CI,-0.88-0.04; I2 = 0.0%), femoral neck (WMD = -0.38, 95% CI,-1.02-0.25; I2 = 0.0%), or total body (WMD = -0.17, 95% CI,-0.51-0.17; I2 = 0.0%) in two randomized controlled trials (RCTs) compared with a placebo. Another two RCTs compared nitrates with alendronate. Nitrates were comparable to alendronate in increasing bone mineral density at lumbar spine (WMD = 0.00, 95% CI,-0.01-0.02; I2 = 0.0%). Besides, the most common adverse effect was headache, contributing to low adherence to therapy. Conclusion: Our meta-analysis showed no association between nitrates use and fractures in observational studies. The results of RCTs on the usage of nitrates and their effects on BMD were inconsistent. High-quality, long-term studies are needed to clarify the efficacy of nitrates for bone health.

Effects of Cilostazol and Isosorbide Mononitrate on Cerebral Hemodynamics in the LACI-1 Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Cerebral small vessel disease-a major cause of stroke and dementia-is associated with cerebrovascular dysfunction. We investigated whether short-term isosorbide mononitrate (ISMN) and cilostazol, alone or in combination, improved magnetic resonance imaging-measured cerebrovascular function in patients with lacunar ischemic stroke. METHODS: Participants were randomized to ISMN alone, cilostazol alone, both ISMN and cilostazol, or no medication. Participants underwent structural, cerebrovascular reactivity (to 6% carbon dioxide) and phase-contrast pulsatility magnetic resonance imaging at baseline and after 8 weeks of medication. RESULTS: Of 27 participants (mean age, 68±7.7; 44% female), 22 completed cerebrovascular reactivity and pulsatility imaging with complete datasets. White matter cerebrovascular reactivity increased in the ISMN (ß=0.021%/mm Hg [95% CI, 0.003-0.040]) and cilostazol (ß=0.035%/mm Hg [95% CI, 0.014-0.056]) monotherapy groups and in those taking any versus no medication (ß=0.021%/mm Hg [95% CI, 0.005-0.037]). CONCLUSIONS: While limited by small sample size, we demonstrate that measuring cerebrovascular function with magnetic resonance imaging is feasible in clinical trials and that ISMN and cilostazol may improve cerebrovascular function. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02481323. URL: www.isrctn.com; Unique identifier: ISRCTN12580546. URL: www.clinicaltrialsregister.eu; Unique identifier: EudraCT 2015-001953-33.

Sustained-release isosorbide mononitrate as adjuvant treatment in isolated systolic hypertension in the elderly.

Hypertension is one of the main cardiovascular risk factors. In the elderly, the most common form is isolated systolic hypertension, a consequence of the increase in arterial stiffness. None of the antihypertensives currently used affects arterial stiffness, whereas nitrates seem to have an effect. The aim of this work was to assess their effect on elderly patients with uncontrolled isolated systolic hypertension, defined as systolic blood pressure over 140 mmHg and diastolic blood pressure under 90 mmHg. The present study is a phase III, randomized, multicenter, double-blind, placebo-controlled clinical trial, conducted at the University Hospital La Princesa in Madrid. Patients of both sexes, aged 65 years or older, with poorly controlled isolated systolic hypertension, were treated with 40-60 mg of sustained-release isosorbide mononitrate or matching placebo for 12 weeks. The main objective was to assess the effect on clinical pulse pressure (PP); in addition, its effect on vascular function was evaluated. Analysis was performed by intention to treat. The study was registered at the European Union Clinical Trials Register (EUDRACT 2012-002988-10) and was funded by the Spanish Ministry of Health. A total of 58 patients with an average age of 77 years were enrolled, 32 were treated with nitrate, and 26 with placebo. No significant differences were found either in PP decline (5.28 vs 7.49 mmHg, p = 0.79) or in other variables, including parameters of vascular function. There were no differences in adverse events. The results of this study have not confirmed the benefit of nitrate treatment in isolated systolic hypertension or the improvement of vascular function.

Un caso atípico de neoplasia de pulmón / An atypical case of lung neoplasia

Introducción: El cáncer de pulmón se considera el tumor maligno que más muertes produce en el mundo, por encima de otros cánceres y en el 90 por ciento de los casos se diagnostica en estadios avanzados. Objetivos: Describir una forma atípica de presentación de una neoplasia de pulmón. Caso clínico: Paciente masculino de 68 años, fumador de más de 37 años, con antecedentes de insuficiencia cardíaca para lo cual llevó tratamiento con nitrosorbide (10 mg) 1 tableta cada 8 horas y aspirina (125 mg) 1 tableta al día. Refirió dolor en miembro inferior izquierdo, intenso que no se aliviaba durante todo el día y se exacerbaba con los movimientos y esfuerzos físicos. Además, presentó aumento de volumen en la región anterior media del tórax, de aproximadamente 15 cm de longitud, dura, dolorosa, de bordes regulares, superficie lisa. No tuvo tos, disnea, fiebre u otra sintomatología. Conclusiones: El paciente tuvo una forma diferente de presentación de la neoplasia de pulmón. No presentó manifestaciones respiratorias que orientaran hacia la identificación de una causa pulmonar. Es necesaria la identificación del patrón cancerígeno, así como su estadiaje para prescribir el tratamiento y conducta adecuada (AU)

Introduction: Lung cancer is considered the malignant tumor that produces more deaths in the world over other cancers and in 90 percent of cases they are diagnosed in advanced stages. Objectives: To describe an atypical form of presentation of lung neoplasia. Clinical case: A 68-year-old male patient, a smoker over 37 years of age, with a history of heart failure for which he was treated with nitrosorbide (10 mg) 1 tablet every 8 hours and aspirin (125 mg) 1 tablet per day. He reported pain in the lower left limb, which was not relieved throughout the day and was exacerbated by physical movements and efforts. In addition, there was an increase in volume in the middle anterior region of the chest, approximately 15 cm long, hard, painful, with regular edges, smooth surface. He had no cough, dyspnea, fever or other symptoms. Conclusions: The patient had a different form of lung neoplasia presentation. He did not present respiratory manifestations that oriented towards the identification of a pulmonary cause. The identification of the carcinogenic pattern is necessary, as well as its staging to prescribe the appropriate treatment and management(AU)

Achieving Optimal Medical Therapy: Insights From the ORBITA Trial.

Background In stable coronary artery disease, medications are used for 2 purposes: cardiovascular risk reduction and symptom improvement. In clinical trials and clinical practice, medication use is often not optimal. The ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) trial was the first placebo-controlled trial of percutaneous coronary intervention. A key component of the ORBITA trial design was the inclusion of a medical optimization phase, aimed at ensuring that all patients were treated with guideline-directed truly optimal medical therapy. In this study, we report the medical therapy that was achieved. Methods and Results After enrollment into the ORBITA trial, all 200 patients entered a 6-week period of intensive medical therapy optimization, with initiation and uptitration of risk reduction and antianginal therapy. At the prerandomization stage, the median number of antianginals established was 3 (interquartile range, 2-4). A total of 195 patients (97.5%) reached the prespecified target of ≥2 antianginals; 136 (68.0%) did not stop any antianginals because of adverse effects, and the median number of antianginals stopped for adverse effects per patient was 0 (interquartile range, 0-1). Amlodipine and bisoprolol were well tolerated (stopped for adverse effects in 4/175 [2.3%] and 9/167 [5.4%], respectively). Ranolazine and ivabradine were also well tolerated (stopped for adverse effects in 1/20 [5.0%] and 1/18 [5.6%], respectively). Isosorbide mononitrate and nicorandil were stopped for adverse effects in 36 of 172 (20.9%) and 32 of 141 (22.7%) of patients, respectively. Statins were well tolerated and taken by 191 of 200 (95.5%) patients. Conclusions In the 12-week ORBITA trial period, medical therapy was successfully optimized and well tolerated, with few drug adverse effects leading to therapy cessation. Truly optimal medical therapy can be achieved in clinical trials, and translating this into longer-term clinical practice should be a focus of future study. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02062593.

The DANish randomized, double-blind, placebo controlled trial in patients with chronic HEART failure (DANHEART): A 2 × 2 factorial trial of hydralazine-isosorbide dinitrate in patients with chronic heart failure (H-HeFT) and metformin in patients with chronic heart failure and diabetes or prediabetes (Met-HeFT).

OBJECTIVES: The DANHEART trial is a multicenter, randomized (1:1), parallel-group, double-blind, placebo-controlled study in chronic heart failure patients with reduced ejection fraction (HFrEF). This investigator driven study will include 1500 HFrEF patients and test in a 2 × 2 factorial design: 1) if hydralazine-isosorbide dinitrate reduces the incidence of death and hospitalization with worsening heart failure vs. placebo (H-HeFT) and 2) if metformin reduces the incidence of death, worsening heart failure, acute myocardial infarction, and stroke vs. placebo in patients with diabetes or prediabetes (Met-HeFT). METHODS: Symptomatic, optimally treated HFrEF patients with LVEF ≤40% are randomized to active vs. placebo treatment. Patients can be randomized in either both H-HeFT and Met-HeFT or to only one of these study arms. In this event-driven study, it is anticipated that 1300 patients should be included in H-HeFT and 1100 in Met-HeFT and followed for an average of 4 years. RESULTS: As of May 2020, 296 patients have been randomized at 20 centers in Denmark. CONCLUSION: The H-HeFT and Met-HeFT studies will yield new knowledge about the potential benefit and safety of 2 commonly prescribed drugs with limited randomized data in patients with HFrEF.

Comparative analysis of cost-effectiveness between isosorbide-5-mononitrate and isosorbide: a retrospective real-world evaluation.

Aim: The cost-effectiveness of isosorbide-5-mononitrate (5-ISMN) and isosorbide dinitrate (ISDN) in real-world use in patients with coronary heart disease (CHD; either angina pectoris or myocardial infarction) was retrospectively compared. Method: In this retrospective real-world evaluation, patients with established CHD satisfying the following criteria were selected from information system of two tertiary hospitals in China: with pharmacy claiming for at least one injection of 5-ISMN or ISDN between July 2008 and May 2017; and, CHD patients. By using propensity score matching (PSM), we compared clinical aspects of efficacy, safety, length of hospital stay and cost during hospitalization between 5-ISMN and ISDN group. All data were processed by R statistical package v.2.13.1 (R Foundation for Statistical Computing, Vienna, Austria). Result: Of 5609 patients selected, 4047 received 5-ISMN and 1562 received ISDN. After PSM, we acquired 1555 pairs based on balancing of age, sex, insurance and comorbidities on admission. The frequency (4.2 ± 6.6-times vs 6.5 ± 9.5-times; p < 0.05) and total dosage (47.5 ± 153.4 vs 136.4 ± 261.0 mg; p < 0.05) of sublingual nitroglycerin use decreased and hypotension incidence lowered (8.0 vs 13.0%; p < 0.05) in 5-ISMN group compared with ISDN group. Hospital stay (16.0 ± 11.3 days vs 17.7 ± 13.2; p < 0.05) and hospitalization expenditure ([the ratio of cost in the study to the average hospitalization cost in the city] [odds ratio: 2.5 vs 2.6; p < 0.05]) were reduced in 5-ISMN group as with that of ISDN group. Moreover, the main component of hospitalization cost was medical consumables and medications in both the groups. Conclusion: In the present retrospective real-world evaluation, by using PSM analysis, we found that newer injection agent of 5-ISMN was associated with fewer use of sublingual nitroglycerin, less hypotension incidence, shorter length of hospital stay and less hospitalization expenditure related to its comparator ISDN in patients with established CHD. Further evaluation and clinical experience are need in different circumference for the usage of ISDN.

[A study on the targeted nanoparticles of isosorbide mononitrate on reducing the levels of inflammatory factors in rabbit models of rhinosinusitis].

Objective: To investigate the effect of isosorbide mononitrate (ISMN) targeted nanoparticles on inflammatory factors of sinusitis by establishing a rabbit model of rhinosinusitis. Methods: Thirty healthy rabbits, male and female, weighing 2.5-3.5 kg, were randomly divided into 6 groups with 5 rabbits in each group. Group A was the control group. The model of rabbit sinusitis was established in group B to F, and CT was used to confirm the model was successful. After placing tubes into the maxillary sinus in the group C to F, saline, 45 mg/ml ISMN, 45 mg/ml ISMN nanoparticles and 45 mg/ml ISMN targeted nanoparticles were used to wash the maxillary sinus, respectively. Blood samples were collected from the ear vein of rabbits on day 7, 14, 21, 28, 35 and 42 after modeling respectively. Changes in the expression levels of inflammatory factors in rabbits during the modeling process and after drug washing were detected by ELISA. After the drug intervention, the maxillary sinus mucosa was taken for real-time quantitative PCR to detect the changes in the mRNA level of inflammatory factors. SPSS 22.0 software was used to process the data. Results: Rabbit model of sinusitis was successfully established. ELISA showed that after the action of ISMN targeted nanoparticles of 1 week (42th day after modeling), the levels of (interleukin, IL) 4, IL-8, IL-17A and interferon γ (IFN-γ) in the blood were lower compared with that of 35th day after modeling, the difference was statistically significant (5.57±1.20 vs 19.73±0.68, 66.41±11.87 vs 154.68±13.13, 17.96±1.87 vs 28.23±0.80, 53.56±5.66 vs 111.93±7.29, all P<0.05). Compared with the ISMN nanoparticles and ISMN, the ISMN targeted nanoparticles reduced the levels of IL-4, IL-8, IL-17A and IFN-γ more obviously, the differences were statistically significant (13.26±1.43 vs 8.81±1.33 vs 7.14±2.16, 89.47±17.80 vs 41.07±7.77 vs 15.84±3.72, 10.28±2.07 vs 3.06±1.62 vs 1.82±0.90, 62.16±6.18 vs 35.12±4.62 vs 27.89±10.18, all P<0.05). Real-Time PCR showed that after the flushing of ISMN targeted nanoparticles, the levels of IL-4, IL-8, IL-17A and IFN-γ mRNA were lowest compared with that of the model group, ISMN nanoparticles and ISMN group. Conclusion: ISMN targeted nanoparticles can reduce the level of inflammatory factors in rabbit sinusitis model.

"Nonsignificant" early repolarization pattern on postresuscitation ECG as a harbinger of impending electrical storm.

We report a 55-year-old man who was resuscitated from out-of-hospital cardiac arrest and subsequently developed three episodes of ventricular fibrillation (VF) on the same day. Early repolarization (ER) pattern was not significant (<0.1 mV) on postresuscitation ECG. However, ER pattern became evident (0.25 mV) before the onset of VF and then completely disappeared. The unusual dynamics of ER pattern observed in the present case could be called "masked" ER syndrome.

Pharmacological prophylaxis versus pancreatic duct stenting plus pharmacological prophylaxis for prevention of post-ERCP pancreatitis in high risk patients: a randomized trial.

BACKGROUND: Acute pancreatitis is a serious complication of endoscopic retrograde cholangiopancreatography (ERCP). The aim of this noninferiority study was to evaluate the effectiveness of pancreatic duct (PD) stenting plus pharmacological prophylaxis vs. pharmacological prophylaxis alone in the prevention of post-ERCP pancreatitis (PEP) in high risk patients. METHODS: In this randomized, controlled, double-blind, noninferiority trial, patients at high risk of developing PEP were randomly allocated to pharmacological prophylaxis (rectal indomethacin, sublingual isosorbide dinitrate, and intravenous hydration with Ringer's lactate) plus PD stenting (group A) or pharmacological prophylaxis alone (group B). The rate and severity of PEP, serum amylase levels, and length of hospital stay after ERCP were assessed. RESULTS: During 21 months, a total of 414 patients (mean age 55.5 ±â€Š17.0 years; 60.2 % female) were enrolled (207 in each group). PEP occurred in 59 patients (14.3 %, 95 % confidence interval [CI] 11.1 % - 17.9 %: 26 patients [12.6 %, 95 %CI 8.6 % - 17.6 %] in group A and 33 [15.9 %, 95 %CI 11.4 % - 21.4 %] in group B). There was no significant difference between the two groups in PEP severity (P = 0.59), amylase levels after 2 hours (P = 0.31) or 24 hours (P = 0.08), and length of hospital stay (P = 0.07). CONCLUSIONS: The study failed to demonstrate noninferiority or inferiority of pharmacological prophylaxis alone compared with PD stenting plus pharmacological prophylaxis in the prevention of PEP in high risk patients.

Cardiac Memory: A Case Report and Review of the Literature.

BACKGROUND: A variety of clinical syndromes can cause T-wave inversion (TWI), ranging from life-threatening events to benign conditions. One benign cause of TWI is cardiac memory, which is characterized by the transient inversion of T-waves following abnormal activation of the ventricles, commonly due to intermittent left bundle branch block (LBBB), tachydysrhythmias, electrical pacing, or ventricular pre-excitation. CASE REPORT: A 72-year-old man presented to the emergency department with chest pain, nausea, vomiting, and headache. Upon arrival, his electrocardiogram (ECG) showed new-onset LBBB with appropriate secondary ST-T wave changes. A subsequent ECG showed disappearance of LBBB and newly inverted T-waves in precordial leads V1-V5, followed by a repeat ECG that again showed LBBB. Serial troponin testing was unremarkable. During hospitalization, echocardiogram and nuclear perfusion stress test were normal. The transient TWIs in this patient were believed to be due to cardiac memory. We performed a literature review and identified 39 published cases of cardiac memory. The most common etiology for cardiac memory was after cardiac pacemaker placement, followed by intermittent LBBB (as was seen in our patient), and post-tachydysrhythmia. Patient ages ranged from 21 to 88 years, with an equal number of cases reported in men and women. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Cardiac memory is a poorly understood, rarely observed phenomenon that can occur in the setting of intermittent LBBB. Testing for acute cardiac ischemia and underlying coronary artery disease is still recommended, as the diagnosis of cardiac memory can only be made after negative workup.