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mortality - Top 30 Publications

Associations Between Marijuana Use and Cardiovascular Risk Factors and Outcomes: A Systematic Review.

Marijuana use is increasing in the United States, and its effect on cardiovascular health is unknown.

The relation between household income and surgical outcome in the Dutch setting of equal access to and provision of healthcare.

The impact of socioeconomic disparities on surgical outcome in the absence of healthcare inequality remains unclear. Therefore, we set out to determine the association between socioeconomic status (SES), reflected by household income, and overall survival after surgery in the Dutch setting of equal access and provision of care. Additionally, we aim to assess whether SES is associated with cause-specific survival and major 30-day complications.

Inhibitors of Trypanosoma cruzi Sir2 related protein 1 as potential drugs against Chagas disease.

Chagas disease remains one of the most neglected diseases in the world despite being the most important parasitic disease in Latin America. The characteristic chronic manifestation of chagasic cardiomyopathy is the region's leading cause of heart-related illness, causing significant mortality and morbidity. Due to the limited available therapeutic options, new drugs are urgently needed to control the disease. Sirtuins, also called Silent information regulator 2 (Sir2) proteins have long been suggested as interesting targets to treat different diseases, including parasitic infections. Recent studies on Trypanosoma cruzi sirtuins have hinted at the possibility to exploit these enzymes as a possible drug targets. In the present work, the T. cruzi Sir2 related protein 1 (TcSir2rp1) is genetically validated as a drug target and biochemically characterized for its NAD+-dependent deacetylase activity and its inhibition by the classic sirtuin inhibitor nicotinamide, as well as by bisnaphthalimidopropyl (BNIP) derivatives, a class of parasite sirtuin inhibitors. BNIPs ability to inhibit TcSir2rp1, and anti-parasitic activity against T. cruzi amastigotes in vitro were investigated. The compound BNIP Spermidine (BNIPSpd) (9), was found to be the most potent inhibitor of TcSir2rp1. Moreover, this compound showed altered trypanocidal activity against TcSir2rp1 overexpressing epimastigotes and anti-parasitic activity similar to the reference drug benznidazole against the medically important amastigotes, while having the highest selectivity index amongst the compounds tested. Unfortunately, BNIPSpd failed to treat a mouse model of Chagas disease, possibly due to its pharmacokinetic profile. Medicinal chemistry modifications of the compound, as well as alternative formulations may improve activity and pharmacokinetics in the future. Additionally, an initial TcSIR2rp1 model in complex with p53 peptide substrate was obtained from low resolution X-ray data (3.5 Å) to gain insight into the potential specificity of the interaction with the BNIP compounds. In conclusion, the search for TcSir2rp1 specific inhibitors may represent a valuable strategy for drug discovery against T. cruzi.


Carotid intima-media thickness (CIMT), as assessed by ultrasonography, has been shown to be directly related to cardiovascular (CV) morbidity and mortality independently of conventional risk factors. Thus, CIMT has been proposed as a marker of CV risk and a surrogate end-point for therapeutic interventions. In the present article we will review available literature about CIMT clinical/prognostic significance in order to offer an updated comprehensive information on this topic. In particular, the anti-atherosclerotic effect of angiotensin II receptor blockers (ARBs) in the hypertensive setting will be addressed, based on findings provided by double blind, randomized, prospective studies comparing CIMT longitudinal changes. Our review, including 8 studies totalling 1,154 hypertensive participants, shows that ARBs are as effective as the other classes of antihypertensive drugs in preventing/regressing subclinical carotid damage and that findings supporting their superiority in this field are limited and not univocal. Future studies aimed to clarify the therapeutic impact of ARBs on CIMT changes and their prognostic implications are warranted.

Characterisation of the "Frequent Exacerbator Phenotype" in Bronchiectasis.

Exacerbations are key events in the natural history of bronchiectasis, but clinical predictors and outcomes of frequently exacerbating patients are not well described.

Preclinical Explorative Assessment of Dimethyl Fumarate-Based Biocompatible Nanolipoidal Carriers for the Management of Multiple Sclerosis.

Multiple sclerosis (MS) is a neurodegenerative disease, where myelin sheath damage occurs due to internal and external factors and it affects especially young population. Dimethyl fumarate (DMF) is a promising agent for MS though associated with concerns like poor brain permeation, multiple dosing and gastro intestinal flushing. The present study attempts to evaluate preclinical performance of specially-designed DMF-based lipoidal-nanoparticles in cuprizone-induced demyelination rodent model. The studies proved the efficacy of lipid-based nanoparticles, containing DMF in once-a-day dosage regimen, over thrice-a-day plain DMF administration on the crucial parameters like motor coordination, grip strength, mortality, body weight and locomotor activity. However, neither blank lipid nor the blank neuroprotective (vitamin A, D and E) loaded nanoparticles were able to elicit any desirable behavioural response during the studies. The histopathological studies showed that the designed once-a-day DMF nanomedicines were well tolerated as well as rejuvenated myelin sheath vis-à-vis plain thrice-a-day regimen. The findings are the "proof of concept" for a biocompatible nanomedicine for MS with a huge promise of effective brain delivery and patient compliance on the grounds of reduction of dosage frequency.

New Treatments for Hereditary Angioedema.

Hereditary angioedema is characterized by severe, episodic edema of the subcutaneous and mucosal tissue. The disease carries significant morbidity and mortality due to involvement of the gastrointestinal tract and upper airway. Recent advances in the treatment of hereditary angioedema include new techniques used to isolate and purify human-derived C1 inhibitor, the production of a recombinant form of C1 inhibitor, and the development of drugs that target the kallikrein-kinin pathway. This paper reviews the mechanisms, efficacy, and adverse reactions associated with these medications.

Pathophysiologic Mechanisms and Current Treatments for Cutaneous Sequelae of Burn Wounds.

Burn injuries are a pervasive clinical problem. Extensive thermal trauma can be life-threatening or result in long-lasting complications, generating a significant impact on quality of life for patients as well as a cost burden to the healthcare system. The importance of addressing global or systemic issues such as resuscitation and management of inhalation injuries is not disputed but is beyond the scope of this review, which focuses on cutaneous pathophysiologic mechanisms for current treatments, both in the acute and long-term settings. Pathophysiological mechanisms of burn progression and wound healing are mediated by highly complex cascades of cellular and biochemical events, which become dysregulated in slow-healing wounds such as burns. Burns can result in fibroproliferative scarring, skin contractures, or chronic wounds that take weeks or months to heal. Burn injuries are highly individualized owing to wound-specific differences such as burn depth and surface area, in addition to patient-specific factors including genetics, immune competency, and age. Other extrinsic complications such as microbial infection can complicate wound healing, resulting in prolonged inflammation and delayed re-epithelialization. Although mortality is decreasing with advancements in burn care, morbidity from postburn deformities continues to be a challenge. Optimizing specialized acute care and late burn outcome intervention on a patient-by-patient basis is critical for successful management of burn wounds and the associated pathological scar outcome. Understanding the fundamentals of integument physiology and the cellular processes involved in wound healing is essential for designing effective treatment strategies for burn wound care as well as development of future therapies. Published 2018. Compr Physiol 8:371-405, 2018.

Hemorrhagic Shock and the Microvasculature.

The microvasculature plays a central role in the pathophysiology of hemorrhagic shock and is also involved in arguably all therapeutic attempts to reverse or minimize the adverse consequences of shock. Microvascular studies specific to hemorrhagic shock were reviewed and broadly grouped depending on whether data were obtained on animal or human subjects. Dedicated sections were assigned to microcirculatory changes in specific organs, and major categories of pathophysiological alterations and mechanisms such as oxygen distribution, ischemia, inflammation, glycocalyx changes, vasomotion, endothelial dysfunction, and coagulopathy as well as biomarkers and some therapeutic strategies. Innovative experimental methods were also reviewed for quantitative microcirculatory assessment as it pertains to changes during hemorrhagic shock. The text and figures include representative quantitative microvascular data obtained in various organs and tissues such as skin, muscle, lung, liver, brain, heart, kidney, pancreas, intestines, and mesentery from various species including mice, rats, hamsters, sheep, swine, bats, and humans. Based on reviewed findings, a new integrative conceptual model is presented that includes about 100 systemic and local factors linked to microvessels in hemorrhagic shock. The combination of systemic measures with the understanding of these processes at the microvascular level is fundamental to further develop targeted and personalized interventions that will reduce tissue injury, organ dysfunction, and ultimately mortality due to hemorrhagic shock. Published 2018. Compr Physiol 8:61-101, 2018.

Differences in mortality in a cohort of cocaine use disorder patients with concurrent alcohol or opiates disorder.

To study mortality in a cohort of cocaine use disorder patients, and compare results in those with concurrent alcohol or opiates disorder.

How We Fall Apart: Similarities of Human Aging in 10 European Countries.

We analyze human aging-understood as health deficit accumulation-for a panel of European individuals, using four waves of the Survey of Health, Aging and Retirement in Europe (SHARE data set) and constructing a health deficit index. Results from log-linear regressions suggest that, on average, elderly European men and women develop approximately 2.5 % more health deficits from one birthday to the next. In nonlinear regressions (akin to the Gompertz-Makeham model), however, we find much greater rates of aging and large differences between men and women as well as between countries. Interestingly, these differences follow a particular regularity (akin to the compensation effect of mortality) and suggest an age at which average health deficits converge for men and women and across countries. This age, which may be associated with human life span, is estimated as 102 ± 2.6 years.

Multiple small bowel perforations due to invasive aspergillosis in a patient with acute myeloid leukemia: case report and a systematic review of the literature.

Invasive aspergillosis (IA) represents a major cause of morbidity and mortality in immunocompromised patients. Involvement of the gastrointestinal tract by Aspergillus is mostly reported as part of a disseminated infection from a primary pulmonary site and only rarely as an isolated organ infection.

Berberine Ameliorates MCAO Induced Cerebral Ischemia/Reperfusion Injury via Activation of the BDNF-TrkB-PI3K/Akt Signaling Pathway.

Cerebral ischemic injury remains associated with high mortality rates and lacks effective therapeutic intervention. Berberine (BBR) possesses anti-oxidant, anti-inflammatory, and anti-tumor activities, as well as potent neuroprotective effects. Although recent studies have examined the neuroprotective effects of berberine, little is known regarding its usefulness in treating cerebral ischemia. Thus, the aim of this study is to investigate the possible effect and the mechanism of berberine against cerebral ischemic injury using the middle cerebral artery occlusion (MCAO) model. Rats were randomly divided into three groups: control group, MCAO group, and MCAO + BBR group. Modified neurological severity score tests (mNSS) and infarct volumes were measured to determine the neuroprotective effects of berberine. Neuronal survival in striatum was examined by TUNEL staining and immunohistochemistry. Western blotting measured the expression of BDNF, TrkB, p-Akt and cleaved caspase-3. The results demonstrated that BBR could significantly protect against MCAO. Berberine also increased the expression of BDNF, TrkB, and p-Akt, which were reduced after MCAO. Furthermore, treatment with BBR declined the apoptosis-related proteins induced by MCAO. However, treatment with LY294002 (PI3K inhibitor) reversed the BBR-induced increases in BDNF and p-Akt proteins and decreased cleaved caspase-3 protein expression in focal cerebral ischemic rats. In summary, our results demonstrated that BBR could exert neuroprotective effects through reduction of striatum apoptosis via the BDNF-TrkB-PI3K/Akt signaling pathway.

Pheochromocytomas and Hypertension.

Pheochromocytomas and paragangliomas (PPGLs) are uncommon catecholamine-producing neuroendocrine neoplasms that usually present with secondary hypertension. This review is to update the current knowledge about these neoplasms, the pathophysiology, genetic aspects and diagnostic and therapeutic algorithms based on scientific literature mostly within the past 3 years.

Mechanical birth-related trauma to the neonate: An imaging perspective.

Mechanical birth-related injuries to the neonate are declining in incidence with advances in prenatal diagnosis and care. These injuries, however, continue to represent an important source of morbidity and mortality in the affected patient population. In the United States, these injuries are estimated to occur among 2.6% of births. Although more usual in context of existing feto-maternal risk factors, their occurrence can be unpredictable. While often superficial and temporary, functional and cosmetic sequelae, disability or even death can result as a consequence of birth-related injuries. The Agency for Healthcare research and quality (AHRQ) in the USA has developed, through expert consensus, patient safety indicators which include seven types of birth-related injuries including subdural and intracerebral hemorrhage, epicranial subaponeurotic hemorrhage, skeletal injuries, injuries to spine and spinal cord, peripheral and cranial nerve injuries and other types of specified and non-specified birth trauma. Understandably, birth-related injuries are a source of great concern for the parents and clinician. Many of these injuries have imaging manifestations. This article seeks to familiarize the reader with the clinical spectrum, significance and multimodality imaging appearances of neonatal multi-organ birth-related trauma and its sequelae, where applicable. Teaching points • Mechanical trauma related to birth usually occurs with pre-existing feto-maternal risk factors.• Several organ systems can be affected; neurologic, musculoskeletal or visceral injuries can occur.• Injuries can be mild and transient or disabling, even life-threatening.• Imaging plays an important role in injury identification and triage of affected neonates.

A Retrospective Assessment of Four Antigen Assays for the Detection of Invasive Candidiasis Among High-Risk Hospitalized Patients.

Because of their high mortality rates and non-specific symptoms, invasive Candida infections pose a huge diagnostic and therapeutic challenge. In this study, we evaluated the three mannan antigen assays Platelia, Platelia Plus and Serion, and the (1-3)-β-D-glucan assay Fungitell in a group of high-risk (hematological and surgical) patients. Test results of 305 patients hospitalized at the Vienna General Hospital and the University Hospital of Innsbruck were retrospectively analyzed. We assessed the test accuracy by means of descriptive statistics. Nine (2.95%) patients were affected by invasive candidiasis (IC), and 25 (8.2%) patients had a probable/possible infection. The majority of patients (271; 88.9%) showed no signs of infection. The Platelia and Serion mannan assays had a low sensitivity (65% and 52%, respectively), but high specificity (98% for both tests). The newer version of the Platelia assay, the Platelia Plus, had a higher sensitivity (85%) but a lower specificity (89%). The sensitivity of the Fungitell assay was high (100%), while its specificity was low (58%). The positive predictive values were 0.48 for the Platelia and 0.41 for the Serion assay, 0.26 for the Platelia Plus and 0.09 for the Fungitell assay. Our limited, retrospective study suggests the efficacy of mannan assays as screening (Platelia Plus) and confirmatory (Serion) tests, while the Fungitell assay can be used to exclude invasive Candida infections.

Elevated levels of serum sclerostin are linked to adverse cardiovascular outcomes in peritoneal dialysis patients.

To investigate the correlation between elevated serum sclerostin levels and chronic kidney disease outcomes for patients receiving peritoneal dialysis (PD).

Characteristics and management of penetrating abdominal injuries in a German level I trauma center.

Penetrating abdominal injuries caused by stabbing or firearms are rare in Germany, thus there is lack of descriptive studies. The management of hemodynamically stable patients is still under dispute. The aim of this study is to review and improve our management of penetrating abdominal injuries.

Comparison of Observed Harms and Expected Mortality Benefit for Persons in the Veterans Health Affairs Lung Cancer Screening Demonstration Project.

Association of Time to Treatment With Short-term Outcomes for Pediatric Patients With Refractory Convulsive Status Epilepticus.

Treatment delay for seizures can lead to longer seizure duration. Whether treatment delay is associated with major adverse outcomes, such as death, remains unknown.

Association Between Fluid Balance and Outcomes in Critically Ill Children: A Systematic Review and Meta-analysis.

After initial resuscitation, critically ill children may accumulate fluid and develop fluid overload. Accruing evidence suggests that fluid overload contributes to greater complexity of care and worse outcomes.

Opioid Use Disorders are Associated with Perioperative Morbidity and Mortality in the Hip Fracture Population.

To determine if opioid use disorders are associated with adverse perioperative outcomes in patients undergoing surgical fixation for proximal femur fractures.

Outcomes Associated With Timing of ERCP in Acute Cholangitis Secondary to Choledocholithiasis.

To determine the outcomes associated with timing of endoscopic retrograde cholangiopancreatography (ERCP) in patients with acute cholangitis due to choledocholithiasis, from a population-based study.

Impact of Computed Tomography Evaluation Before Colonoscopy for the Management of Colonic Diverticular Hemorrhage.

The purpose of this study was to investigate and summarize our experience of a standardized strategy using computed tomography (CT) followed by colonoscopy for the assessment of colonic diverticular hemorrhage with focus on a comparison of CT and colonoscopy findings in patients with colonic diverticular hemorrhage.

Hypoalbuminemia is Associated With Significantly Higher Liver Transplant Waitlist Mortality and Lower Probability of Receiving Liver Transplant.

To evaluate the predictive value of hypoalbuminemia on liver transplant (LT) waitlist survival and probability of receiving LT among adults with end-stage liver disease (ESLD).

Sarcopenia in Children With End-Stage Liver Disease.

Sarcopenia, reflected by decreased psoas muscle surface area (PMSA), has been identified as a novel and independent predictor of wait-list mortality and outcomes in adult liver transplantation (LT). We hypothesized that children with end-stage liver disease (ESLD) would have smaller PMSA than healthy controls.

Update on Neonatal Herpes Simplex Epidemiology in the Netherlands: A Health Problem of Increasing Concern?

This paper provides an update on the incidence of neonatal herpes, guideline adherence by health care professionals (HCP), and trends in genital herpes simplex virus (HSV) infection during pregnancy in the Netherlands.

Moxifloxacin in Pediatric Patients with Complicated Intra-Abdominal Infections: Results of the MOXIPEDIA Randomized Controlled Study.

This study was designed to evaluate primarily the safety and also the efficacy of moxifloxacin (MXF) in children with complicated intra-abdominal infections (cIAIs).

The effects of physical activity on survival in patients with colorectal cancer.

Mortality from colorectal cancer has been declining over the past 20 years due to improvements in screening and treatment. Physical activity improves patient quality of life, slows functional decline, and reduces all-cause mortality. Although some patients may have difficulty participating in physical activity, clinicians should always try to incorporate exercise into a management plan for patients who have survived colorectal cancer.

Nonalcoholic steatohepatitis: the new frontier for liver transplantation.

Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease globally and nonalcoholic steatohepatitis is projected to become the most common indication for liver transplantation. The purpose of this review is to highlight key issues surrounding NAFLD as an indication for liver transplantation, including its increasing prevalence, outcomes related to liver transplantation, development of post liver transplant NAFLD and NAFLD in the liver donor pool.