Mitochondrial dysfunction in metabolism and ageing: shared mechanisms and outcomes?

Mitochondria are key in the metabolism of aerobic organisms and in ageing progression and age-related diseases. Mitochondria are essential for obtaining ATP from glucose and fatty acids but also in many other essential functions in cells including aminoacids metabolism, pyridine synthesis, phospholipid modifications and calcium regulation. On the other hand, the activity of mitochondria is also the principal source of reactive oxygen species in cells. Ageing and chronic age-related diseases are associated with the deregulation of cell metabolism and dysfunction of mitochondria. Cell metabolism is controlled by three major nutritional sensors: mTOR, AMPK and Sirtuins. These factors control mitochondrial biogenesis and dynamics by regulating fusion, fission and turnover through mito- and autophagy. A complex interaction between the activity of these nutritional sensors, mitochondrial biogenesis rate and dynamics exists and affect ageing, age-related diseases including metabolic disease. Further, mitochondria maintain a constant communication with nucleus modulating gene expression and modifying epigenetics. In this review we highlight the importance of mitochondria in ageing and the repercussion in the progression of age-related diseases and metabolic disease.     

Pediatric heart transplantation—indications and outcomes in the current era

Pediatric heart transplantation (HTx) remains an important treatment option in the care of children with end-stage heart disease, whether it is secondary to cardiomyopathy or congenital heart disease (CHD). As surgical outcomes for CHD have improved, the indications for pediatric HTx have had to be dynamic, not only for children with CHD but also for the growing population of adults with CHD. As the field of pediatric HTx has evolved, the outcomes for children undergoing HTx have improved. This is undoubtedly due to the continued research efforts of both single-center studies, as well as research collaboratives such as the International Society for Heart and Lung Transplantation (ISHLT) and the Pediatric Heart Transplant Study (PHTS) group. Research collaboratives are increasingly important in pediatric HTx as single center studies for a limited patient population may not elicit strong enough evidence for practice evolution. Similarly, complications that limit the long term graft survival may occur in a minority of patients thus pooled experience is essential. This review focuses on the indications and outcomes for pediatric HTx, with a special emphasis on studies generated by these research collaboratives.     

Coronary angioplasty in spontaneous coronary artery dissection—Strategy and outcomes

ObjectiveTo study the clinical, angiographic and technical characteristics of patients with spontaneous coronary artery dissection (SCAD) undergoing percutaneous coronary intervention (PCI).MethodsThis was a retrospective single center study where patients with angiographically confirmed SCAD undergoing PCI over a period of 4 years (2013–2017) were analyzed. We also sought to identify the clinical and angiographic predictors of procedural failure during PCI.ResultsThere were a total of 42 patients with angiographically confirmed SCAD during the study period of which 16 patients (38.1%) underwent PCI. 14 out of the 16 patients (87.5%) taken up for PCI had technical success. In all patients the lesion was initially attempted to cross with a floppy wire and if unsuccessful it was escalated to a hydrophilic wire and finally to a stiff wire The SCAD lesion was crossed with a floppy wire in 71.4% of patients, with a hydrophilic wire in 14.2% and a stiff wire in 7.1% of patients. Wire escalation was required in 5 patients (31.3%) and in 60% of cases there was a technical success after wire escalation. Presence of diabetes mellitus, hypertension, dyslipidemia, smoking, coexisting atherosclerosis, diffuse nature of the lesion, and baseline Thrombolysis in Myocardial Infarction (TIMI) ≤ 2 flow did not predict procedural failure during PCI.ConclusionPCI in SCAD is associated with a fair rate of technical success in our population. Choosing an initial floppy wire and then escalating to a hydrophilic wire followed by a stiff wire is an optimal revascularization strategy.     

Pancreatitis in pregnancy：etiology,diagnosis, treatment,and outcomes

BACKGROUND: Acute pancreatitis in pregnancy is a rare and dangerous disease. This study aimed to examine the etiology, treatment, and outcomes of pancreatitis in pregnancy.
METHOD: A total of 25 pregnant patients diagnosed with pancreatitis during the period of 1994 and 2014 was analyzed retrospectively.
RESULTS: The pregnant patients were diagnosed with pancre-atitis during a period of 21 years. Most (60%) of the patients were diagnosed with pancreatitis in the third trimester. The mean age of the patients at presentation was 25.7 years, with a mean gestational age of 24.4 weeks. Abdominal pain occurred in most patients and vomiting in one patient was associated hyperemesis gravidarum. The common cause of the disease was gallstone-related (56%), followed by alcohol-related (16%), post-ERCP (4%), hereditary (4%) and undetermined condi-tions (20%). The level of triglycerides was minimally high in three patients. ERCP and wire-guided sphincterotomy were performed in 6 (43%) of 14 patients with gallstone-related pancreatitis and elevated liver enzymes with no complications. Most (84%) of the patients underwent a full-term, vaginal delivery. There was no difference in either maternal or fetal outcomes after ERCP.
CONCLUSIONS: Acute pancreatitis is rare in pregnancy, oc-curring most commonly in the third trimester, and gallstones are the most common cause. When laparoscopic cholecystec-tomy is not feasible and a common bile duct stone is highly suspected on imaging, endoscopic sphincterotomy or stenting may help to prevent recurrence and postpone cholecystectomy until after delivery.     

Do guidelines improve the process and outcomes of care in delirium?

OBJECTIVE: To develop consensus guidelines for management of delirium and to assess their effectiveness in improving the outcomes and process of care in delirium. METHOD: Guidelines for delirium were developed following a literature search and a formal multi-disciplinary consensus process using a two-stage Delphi technique. The process and outcomes of patients with delirium were then observed in a 'before' (211 patients) and an 'after' study (125 patients). Three levels of intervention were made in the 'after' study. (i) Feedback of baseline data only (low intensity intervention). (ii) As in (i), but also formal distribution of the guidelines to nurses and doctors (medium intensity intervention). (iii) As in (ii), but in addition the guidelines were reinforced with teaching sessions for the nurses and doctors (high intensity intervention). SETTING: Older people (aged over 65 years) with delirium admitted to acute medical or acute elderly care wards in five district general hospitals in England. RESULTS: Only in the high intervention group was there an improvement in process and outcome of care, but this failed to reach statistical significance. CONCLUSION: Delirium is a poorly managed condition in older people and guidelines alone fail to improve the process and outcomes of care.     

Serological lymphocytic activity and patient-reported outcomes in Sjögren’s syndrome

Clinical Rheumatology - This study was set to investigate whether serum markers of lymphocytic activity are associated with patient-reported outcomes in Sjögren’s syndrome (SS)....     

Uncrossable and undilatable lesions—A practical approach to optimizing outcomes in PCI

Uncrossable lesions are those that cannot be crossed with a balloon after successful guidewire crossing. These lesions are challenging and are commonly encountered in tortuous and calcified arteries as well as chronic total occlusions. They are the second most common barrier to successful PCI in CTO intervention after inability to cross the CTO segment with a guidewire. Procedures involving balloon uncrossable lesions during routine and CTO PCI utilise longer procedural times, radiation dose and contrast volumes with a lower likelihood of procedural success. In this article, we describe a pragmatic approach of managing balloon uncrossable lesions utilising the most contemporary equipment available in an algorithmic fashion beginning with simple, cost effective techniques right up to complex strategies for advanced operators. In addition, some of these lesions, even when crossed by any technique, they may remain difficult to dilate and prepare for stent insertion. We describe an approach of how to manage these undilatable lesions.     

How do you feel about...? Health outcomes in late life and self-perceptions of health and well-being

Research has shown over the years that the self-perceptions of older adults about their health and well-being may be at least as important as objective data for predicting the course of their health over time. I review a series of studies that span 30 years in which I and my colleagues have asked older adults in the community about their self-rated health and well-being across a spectrum of parameters, including self-rated health, social support, and mood (both negative and positive), and about whether their basic needs are being met. The social environment shapes perceptions of health and well-being, as does the body. Feelings, such as feelings about health and well-being, are therefore a key (but not the only) psychological-behavioral bridge between the body (genome and physiology) and society (environmental stressors and social context). Following a review of these studies, I attempt to place these perceptions of health and well-being in a social context, a context critical to understanding the consistency and strength of these studies (and others performed over many years) documenting the association between answers to the question "How do you feel about...?" and health outcomes over time.     

Influence of cirrhosis in cardiac surgery outcomes

Liver cirrhosis has evolved an important risk factor for cardiac surgery due to the higher morbidity and mortality that these patients may suffer compared with general cardiac surgery population.The presence of contributing factors for a poor outcome,such as coagulopathy,a poor nutritional status,an adaptive immune dysfunction,a degree of cirrhotic cardiomyopathy,and a degree of renal and pulmonary dysfunction,have to be taken into account for surgical evaluation when cardiac surgery is needed,together with the degree of liver disease and its primary complications.The associated pathophysiological characteristics that liver cirrhosis represents have a great influence in the development of complications during cardiac surgery and the postoperative course.Despite the population of cirrhotic patients who are referred for cardiac surgery is small and recommendations come from small series,since liver cirrhotic patients have increased their chance of survival in the last 20 years due to the advances in their medical care,which includes liver transplantation,they have been increasingly considered for cardiac surgery.Indeed,there is an expected rise of cirrhotic patients within the cardiac surgical population due to the increasing rates of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis,especially in western countries.In consequence,a more specific approach is needed in the assessment of care of these patients if we want to improve their management.In this article,we review the pathophysiology and outcome prediction of cirrhotic patients who underwent cardiac surgery.     

Hepatitis B virus genotypes in southwest Iran： Molecular, serological and clinical outcomes

AIM： To investigate the associations of hepatitis B virus （HBV） genotype with HBeAg and anti-HBe status, alanine aminotransferase （ALT） levels and HBV-DNA detection in different groups of HBV-infected patients in southwest Iran. METHODS： A total of 89 HBsAg-positive serum samples were collected from the same number of patients. All sera were then investigated to determine HBV DNA and serological markers. For all the polymerase chain reaction （PCR）-positive samples, biochemical, histopathological assays and genotyping were also performed. RESULTS： Genotype D was the only type of HBV foundin different clinical forms of acute and chronic infections. There was a high prevalence of HBeAg-negative HBV- infected patients with chronic hepatitis （52.7%）. Out of 55 patients with chronic hepatitis, seven （12.7%） were diagnosed with cirrhosis. A significant association between the presence of anti-HBe antibody and an increase in ALT level, among either HBeAg-negative （P = 0.01） or HBeAg-positive （P = 0.026） patients, was demonstrated. No significant differences were observed between the clinical outcomes of HBeAg-positive and -negative individuals （P = 0.24）. CONCLUSION： Genotype D has been recognized as the only type of HBV found in different clinical forms of HBV infections, including cirrhosis, among the residents of southwest Iran. Anti-HBe possibly plays a role in disease progression in some patients with chronic hepatitis, at least for a period of disease.     

Diagnosis delay in patients with ankylosing spondylitis: factors and outcomes—an Indian perspective

This study focuses on the causes and consequences of delay in diagnosis of ankylosing spondylitis (AS). Seventy consecutive patients presenting at a rheumatology clinic in India were studied. Mean (±S.D) delay in diagnosis was 6.9 (±5.2) years. The main cause of delay was incorrect diagnosis as non-specific back pain (19/54, 35.1%), degenerative disc disease (14/54, 25.9%), rheumatoid arthritis (11/54, 20.37%), and tuberculosis of spine (9/54, 16.6%) in that order, for which the patient received prolonged treatment. Absence of extra-articular manifestations and juvenile age also significantly correlated with diagnostic delay. Delay in diagnosis resulted in significantly worse disease activity index (BASDAI), functional index (BASFI), and damage index (BASMI). Most incorrect initial diagnoses were made by orthopedicians (75.9%), followed by general physician (50%), and rheumatologist (12%). Continuing medical education workshops with a focus on clinical diagnosis of inflammatory back pain may help in early diagnosis of AS.     

G protein receptor kinase 4 polymorphisms: β-Blocker Pharmacogenetics and treatment-related outcomes in Hypertension

G protein-coupled receptor kinases (GRKs) are important regulatory proteins for many G protein-coupled receptors, but little is known about GRK4 pharmacogenetics. We hypothesized that 3 nonsynonymous GRK4 single-nucleotide polymorphisms, R65L (rs2960306), A142V (rs1024323), and A486V (rs1801058), would be associated with blood pressure response to atenolol, but not hydrochlorothiazide, and would be associated with long-term cardiovascular outcomes (all-cause death, nonfatal myocardial infarction, nonfatal stroke) in participants treated with an atenolol-based versus verapamil-SR-based antihypertensive strategy. GRK4 single-nucleotide polymorphisms were genotyped in 768 hypertensive participants from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) trial. In whites and blacks, increasing copies of the variant 65L-142V haplotype were associated with significantly reduced atenolol-induced diastolic blood pressure lowering (-9.1±6.8 versus -6.8±7.1 versus -5.3±6.4 mm Hg in participants with 0, 1, and 2 copies of 65L-142V, respectively; P=0.0088). One thousand four hundred sixty participants with hypertension and coronary artery disease from the INternational VErapamil SR/Trandolapril STudy (INVEST) were genotyped, and variant alleles of all 3 GRK4 single-nucleotide polymorphisms were associated with increased risk for adverse cardiovascular outcomes in an additive fashion, with 486V homozygotes reaching statistical significance (odds ratio, 2.29 [1.48-3.55]; P=0.0002). These effects on adverse cardiovascular outcomes were independent of antihypertensive treatment. These results suggest that the presence of GRK4 variant alleles may be important determinants of blood pressure response to atenolol and risk for adverse cardiovascular events. The associations with GRK4 variant alleles were stronger in patients who were also ADRB1 389R homozygotes, suggesting a potential interaction between these 2 genes.     

Clinical characteristics and outcomes of patients with extended-spectrum ��-lactamase-producing bacteremias in the emergency department

Extended-spectrum β-lactamase (ESBL)-producing bacteria have been spreading from hospitals to communities. Despite this, there are limited emergency department (ED) patient-based studies about these bacteremias. A retrospective matched case-control study with a ratio of 1:3 was conducted at a university hospital. The case group consisted of patients aged >16 years with ESBL-producing bacteremias in the ED. Patients matched for age and sex with non-ESBL-producing bacteremias were sampled as the control group. Finally, 64 episodes of ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis bacteremias were included in our study. The median age of case patients was 71 years, and 29 (45.3%) were males. The most common type of infection was urinary tract infection (71.9%), followed by intra-abdominal infection (12.5%). Inappropriate empirical antibiotics therapy was prescribed in 87.5% of case patients, which was significantly higher than the control group (13.0%; p < 0.001). Patients with inappropriate empirical antibiotics had a significantly longer hospital stay than those with appropriate empirical antibiotics (p < 0.001). Multivariate analysis showed that hospital-acquired infection, urinary catheterization, and previous antibiotics use were independent risk factors for the acquisition of ESBL-producing bacteremia. The 28-day mortality rate of case patients was 18.8%. Whether they received appropriate empirical antibiotics treatment or not, there was no statistical difference in the mortality of patients with ESBL-producing bacteremias (p = 0.167). To face these emerging multidrug-resistant bacteria and to guide the empirical antibiotics therapy, it is crucial for emergency physicians to recognize the characteristics and risk factors for ESBL-producing organisms.     

Long-term statin safety and efficacy in secondary prevention: can combination therapy improve outcomes?

The use of statins has been associated with substantial reductions in vascular morbidity and mortality. The Prospective Pravastatin Pooling Project (PPP) looked at the long-term safety and efficacy of statins in secondary prevention, based on pooled results from three key statin trials. PPP revealed a highly significant relative risk reduction in total mortality, and demonstrated that pravastatin has a similar incidence of muscle-related side effects as placebo. It has been speculated that treatment with statins in combination with other cardiovascular drugs may have a synergistic effect on reduction of cardiovascular complications. However, for ethical reasons, evidence can only ever be sought from sub-group analyses or meta-analyses of existing studies. Recent studies have focused on statins plus acetyl- salicylic acid (ASA, aspirin). Evidence suggests that a combination of statins with ASA provides a cardiovascular risk reduction that is superior to the respective monotherapy. Thus, statins effectively reduce further cardiovascular morbidity and mortality as well as total mortality in patients with manifest coronary artery disease (CAD) or at high risk, also they act in synergy with ASA and they are safe.     

Behçet's disease phenotypes and clinical outcomes: A cohort study in egyptian patients

IntroductionBehçet's disease (BD) is a systemic inflammatory disease with various presentations. The data on the course of BD in Egyptian patients are limited.ObjectivesThe objective of the study was to describe the evolution and association of the different phenotypes of BD.Material and methodsThis chronological cohort study included adult Egyptian patients suffering from BD. Demographic data and the chronological order of the disease's manifestations were collected.ResultsThe study included 233 patients. Their mean age at the onset of the disease was 26.3 ± 6.9 years. The mean duration from onset of the disease to meeting the criteria was 11.2 ± 30.3 months. The mean duration of the disease was 96.8 ± 72.2 months. On onset of the disease, the most common phenotypes were mucocutaneous (84.5%), musculoskeletal (15.9%), ocular (14.6%) and peripheral venous disease (PVD) (7.3%); on the other hand, pulmonary, peripheral arterial and great vessel phenotypes evolved several years after onset of the disease. The mean time from meeting the criteria to the evolution of a new phenotype was 53.8 ± 58.7 months. Associations between the different phenotypes were observed: PVD and superficial thrombophlebitis, peripheral arterial disease and PVD; another association was also observed between aortic involvement and cerebrovascular disease.ConclusionBD could continue to evolve several years after onset of the disease, making the previous belief about BD yield questionable. BD tends to respect the anatomy of the affected system. Some phenotypes tend to coexist, suggesting a shared aethiopathogeny and that the disease is of a systemic nature.