Evaluation of Routine Coronary Angiography Before Pulmonary Thromboendarterectomy.

BACKGROUND: At the University of California, San Diego, routine coronary angiography has generally been performed in men 40 years of age and older and women 45 years of age and older before pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension (CTEPH). The prevalence of significant coronary artery disease (CAD) in this population has not been evaluated, however, and the optimal screening strategy has not been established. This study sought to evaluate whether the current approach may be better optimized on the basis of cardiac risk factors. METHODS: This study included 462 consecutive patients with CTEPH who were undergoing preoperative coronary angiography for pulmonary thromboendarterectomy. Baseline demographic and medical information was recorded. Major cardiac risk factors included: diabetes, hypertension, hyperlipidemia, body mass index 25 kg/m2 or greater, tobacco use, and family history of CAD. Charts were then reviewed for presence of significant CAD and revascularization. RESULTS: Significant CAD was found in 13.4% of patients who underwent routine preoperative coronary angiography; it was present in only 5% of patients younger than 50 years of age, compared with 16% of patients 50 years old and older. No patient younger than 50 years of age without cardiac risk factors was found to have significant CAD. Furthermore, in patients younger than 50 years of age, significant CAD was found only among those with 3 or more major risk factors. CONCLUSIONS: In patients younger than 50 years of age with CTEPH, the prevalence of significant CAD was low. Omitting preoperative coronary angiography in this subset of patients is reasonable when no coronary risk factors are present. Preoperative coronary angiography is warranted in individuals 50 years of age and older, as well as in those younger than 50 years who have significant risk factors for CAD.

Circadian regulation of breath alcohol concentration.

STUDY OBJECTIVES: The role of the circadian clock in regulating blood/breath alcohol levels after consuming alcohol is uncertain. Our goal was to evaluate the degree to which the circadian system regulates breath alcohol concentration (BrAC) pharmacokinetic parameters. METHODS: Twenty healthy adults aged 21-30 years took part in a 4-day laboratory study. A 40-h constant routine procedure was used to assess circadian rhythms. Every 4 h, participants were given a fixed oral dose of alcohol with breathalyzer measurements taken every 5 min to construct BrAC curves. Sinusoidal models were used to test for circadian variation of the peak BrAC, the time to reach peak BrAC, the absorption rate, the elimination rate, and the time for BrAC to return to zero after alcohol was ingested. RESULTS: A significant circadian rhythm was detected for group-averaged peak BrAC values and the time for BrAC to return to zero, but not other BrAC variables. Peak BrAC values were lowest in the evening near the peak of the core body temperature rhythm and nadir of the salivary cortisol rhythm. Peak BrAC values increased during the night and reached their highest levels in the morning and afternoon. The time needed for BrAC to return to zero was also longest in the late morning and afternoon. CONCLUSION: The circadian system modulates some BrAC pharmacokinetic parameters. In normally entrained individuals, taking the same oral dose of alcohol at different times of day can result in different BrAC responses. These findings have potential implications for alcohol-related accidents and alcohol toxicity.

Impact of the COVID-19 pandemic on paediatric orthopaedic trauma workload in central London: a multi-centre longitudinal observational study over the "golden weeks".

Background and purpose - The COVID-19 pandemic has been recognised as an unprecedented global health crisis. This study assesses the impact on a large acute paediatric hospital service in London, evaluating the trends in the acute paediatric orthopaedic trauma referral caseload and operative casemix before (2019) and during (2020) COVID-19 lockdown. Patients and methods - A longitudinal retrospective observational prevalence study of both acute paediatric orthopaedic trauma referrals and operative caseload was performed for the first 6 "golden weeks" of lockdown. These data were compared with the same period in 2019. Statistical analyses included median (± median absolute deviation), risk and odds ratios as well as Fisher's exact test to calculate the statistical significance, set at p ≤ 0.05. Results - Acute paediatric trauma referrals in 2020 were reduced by two-thirds compared with 2019 (n = 302 vs. 97) with a halving risk (RR 0.55) and odds ratios (OR 0.43) of sporting-related mechanism of injuries (p = 0.002). There was a greater use of outpatient telemedicine in the COVID-19 period with more Virtual Fracture Clinic use (OR 97, RR 84, p < 0.001), and fewer patients being seen for consultation and followed up face to face (OR 0.55, RR 0.05, p < 0.001). Interpretation - The impact of the COVID-19 pandemic has led to a decline in the number of acute paediatric trauma referrals, admissions, and operations during the COVID period. There has also been a significant change in the patient pathway with more being reviewed via the means of telemedicine to reduce the risk of COVID-19 transmission and exposure. More work is required to observe for similar trends nationwide and globally as the pandemic has permanently affected the entire healthcare infrastructure.

Should women have different ECG criteria for CRT than men?

One of the key aspects of heart failure management is whether patients should be considered for device therapy. Clinical trials, which have employed QRS duration and morphology as measures of left ventricular dyssynchrony, have demonstrated the morbidity and mortality benefit of cardiac resynchronization therapy. Women, however, are underrepresented in these trials, the basis of which current guidelines and standards of care are derived. Despite low enrollment of women, several studies highlight the statistically significant improvement in risk reduction that women gain from cardiac resynchronization therapy compared to men. This review discusses the foundation for current guidelines and the building evidence that women may reap more benefit from cardiac resynchronization therapy than men. Given these data, a more individualized approach should be considered in prescribing this device therapy in the future, particularly in women.

Opportunities for Improvement in the Care of Patients Hospitalized for Inflammatory Bowel Disease-Related Colitis.

BACKGROUND: Algorithms for the diagnosis, management, and follow-up have been proposed for patients hospitalized for inflammatory bowel disease (IBD) colitis flare. The degree to which providers adhere to these algorithms is unknown. This study evaluated the quality of care in IBD patients hospitalized for disease-associated exacerbations and factors correlated with higher degrees of care. METHODS: Retrospective chart review of 34 patients during 60 admissions to the medicine service for IBD colitis exacerbation between 2005 and 2012 at the Veterans Affairs San Diego Medical Center. Examined factors included laboratory testing, timing of consultation and intravenous steroids, abdominal imaging, endoscopic examination, venous thromboembolism (VTE) prophylaxis, narcotic use, Clostridium difficile and cytomegalovirus testing, symptomatology at discharge, timing of follow-up, and rates of readmission and mortality. RESULTS: Quality of care varied among the factors studied, ranging from 30.5 % for pharmacologic VTE prophylaxis to 84.7 % for gastroenterology consultation within 24 h. Of 60 admissions, 22 % were not tested for C. difficile. Fifteen percent of patients were discharged before meeting commonly used discharge criteria. Eighty percent were seen in clinic at any time post-discharge; 6.7 % were readmitted; 10 % were lost to follow-up; 1.7 % opted for outside follow-up; and 1.7 % expired. CONCLUSIONS: The quality of care for patients admitted with IBD colitis flares is variable. These data outline opportunities for improvement, particularly in regard to pain management, VTE prophylaxis, and follow-up. Further studies are needed to test intervention strategies for practice improvement.

Current Understanding of the Compensatory Actions of Cardiac Natriuretic Peptides in Cardiac Failure: A Clinical Perspective.

Natriuretic peptides play a crucial role in maintaining cardiovascular homeostasis. Among their properties are vasodilation, natriuresis, diuresis, and inhibition of cardiac remodeling. As heart failure progresses, however, natriuretic peptides fail to compensate. Knowledge of their processing and signaling pathways has guided the development of pharmacological therapies aimed at bolstering their effects. The drugs that have achieved the most clinical success have also stirred the most controversy. Nesiritide, the synthetic B-type natriuretic peptide, yielded significant symptomatic relief and improved haemodynamics but its use was plagued with questions surrounding its possibly harmful impact on renal function. More recently, compounds containing inhibitors of neprilysin, the enzyme responsible for degrading natriuretic peptides, have demonstrated morbidity and mortality benefit, but have also been linked to possible negative side effects. Clearly, potentiating the actions of natriuretic peptides for the benefit of patients is not as simple as just raising their serum concentration. This article reviews the current understanding of the compensatory actions of cardiac natriuretic peptides in heart failure and how this knowledge is revolutionizing heart failure therapy.

Prevalence of coronary artery-pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension.

This study sought to determine the prevalence of coronary artery-pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to correlate their presence with the degree of clot burden. CTEPH is a treatable cause of severe pulmonary hypertension and right heart failure. Bronchopulmonary collateral vessels have been used as a supplementary diagnostic and prognostic tool for this disease. Coronary artery-pulmonary artery collaterals in this population have not been described. The coronary angiograms of 300 consecutive patients with CTEPH evaluated for pulmonary thromboendarterectomy (PTE) between January 1, 2007, and May 1, 2014, were examined. Of these patients, 259 (50% male; mean age, 58.3 ± 10.6 years) had cineangiographic images deemed adequate to definitively assess for the presence of coronary artery-pulmonary artery collaterals and were included in the final analyses. Pulmonary angiogram reports were reviewed for extent of pulmonary artery obstruction. The coronary angiograms of 259 age- and sex-matched control patients were also examined. Among 259 CTEPH patients with definitive imaging, 34 coronary artery-pulmonary artery collaterals were found in 28 patients (10.8%), versus 1 coronary artery-pulmonary artery collateral among control subjects (0.4%; P < 0.001). Compared with CTEPH patients without collaterals, patients with collaterals had a significantly higher prevalence of total occlusion of their right or left main pulmonary artery (P < 0.001) or lobar arteries (P < 0.001). In conclusion, the prevalence of coronary artery-pulmonary artery collaterals in CTEPH patients undergoing coronary angiography for possible PTE is approximately 11%. These vessels are associated with more severe pulmonary artery occlusion.

Personalized CHF treatment: PCT to guide therapy in heart failure patients.

Sorting out the etiology of dyspnea in patients with a history of heart failure is not always straightforward. Although an acute heart failure exacerbation would seem to be easy to distinguish from an acute respiratory illness, data from objective clinical studies has shown otherwise. Procalcitonin (PCT), a biomarker that rises in the setting of bacterial infection, carries great potential for guiding the diagnosis and treatment of heart failure patients with possible acute respiratory infection. In this issue of the International Journal of Cardiology, Kutz et al. demonstrated that patients with a history of heart failure and suspected lower respiratory tract infection experienced reduced antibiotic duration and superior outcomes with PCT-guided therapy. The results in this subset of heart failure patients from the ProHOSP study were consistent with the results seen in the overall study population. This study points to the need for a randomized controlled trial in a broader population of heart failure patients with acute dyspnea, to further define the prominent role that PCT can play in more personalized medical treatments that can improve patient outcomes.

Periosteal tension band fixation of a pronation external rotation type fracture of the ankle in a child.

Interposed soft tissues can block the anatomical reduction of displaced physeal fractures in children and may necessitate surgical removal. The authors describe a new technique in which they surgically freed the interposed distal-based periosteal flap in an irreducible Salter-Harris type II fracture in a 6-year-old boy and then used this flap in a tension band mode to stabilize the fracture. The thick periosteal flap was held under tension and was reattached to the tibial metaphysis using a 3.5-mm cortical screw and a multi-spiked soft tissue washer. The fracture healed satisfactorily, and the patient regained his ankle function and range of motion by 2 months. Periosteal tension band fixation achieves good skeletal stabilization and avoids more than 1 surgical incision.

Necrotising fasciitis: a series of seven cases.

Necrotising fasciitis of the extremities is a rapidly progressive, potentially life threatening soft tissue infection. Early diagnosis, aggressive surgical and critical care management is vital in preventing mortality. This series reports the clinical presentation, behaviour of inflammatory markers, histological, microbiological and radiological findings in seven cases, which presented to our orthopaedic unit over the last one year. Seven patients (4 male and 3 female) were included. Usual presentation was spreading erythema and pain. Duration of symptoms varied from 3 to 14 days. All except one case affected the lower limbs. The average Laboratory risk indicator for necrotising fasciitis (LRINEC) score on the day of presentation was 5. Imaging demonstrated subcutaneous oedema, fluid and air pockets in muscular planes. Group A beta haemolytic Streptococcus was the most common organism isolated from culture. Treatment modalities included antibiotics, immunoglobulins and surgical debridement. Four of the patients showed full remission. However, three (one with pre-existing carcinoma) of them succumbed to the condition.

Linaclotide: evidence for its potential use in irritable bowel syndrome and chronic constipation.

Both irritable bowel syndrome (IBS), characterized by chronic and recurrent abdominal pain and altered bowel habits, and functional constipation are highly prevalent gastrointestinal problems for which many patients seek medical advice. A diverse number of treatment approaches are currently recommended to treat persons with chronic constipation as well as patients with IBS in which constipation is the main gastrointestinal symptom (IBS-C). These approaches have had somewhat limited success, and many patients remain dissatisfied with available therapy. Recently, linaclotide, a novel intestinal secretagogue, which works by activating the guanylate cyclase C receptor on the luminal surface of the intestinal epithelium, has been demonstrated to be efficacious in patients with both chronic functional constipation and with IBS-C in a series of randomized, placebo-controlled studies in these populations. Evidence for this assertion is provided in this systematic review of the pharmacologic properties of this novel agent and the published pivotal studies which support the efficacy of this agent in targeted populations.

Nausea and vomiting of pregnancy.

Nausea and vomiting are common experiences in pregnancy, affecting 70% to 80% of all pregnant women. Various metabolic and neuromuscular factors have been implicated in the pathogenesis of nausea and vomiting of pregnancy (NVP) and hyperemesis gravidarum (HG), an entity distinct from NVP. However, their exact cause is unknown. Consequently, treatment of NVP and HG can be difficult, as neither the optimal targets for treatment nor the full effects of potential treatments on the developing fetus are known. This article reviews the epidemiology, pathology, diagnosis, outcomes, and treatment of NVP and HG.

The pharmacokinetics, pharmacodynamics, clinical efficacy, safety and tolerability of linaclotide.

INTRODUCTION: Linaclotide is a novel intestinal secretagogue that is in the advanced stages of development for the treatment of irritable bowel syndrome with constipation (IBS-C) and chronic constipation. These functional gastrointestinal disorders are highly prevalent in adults and children and often do not respond satisfactorily to available treatments. Linaclotide appears to be a promising new agent for patients who are not satisfied with currently available agents. AREAS COVERED: This article is formed from a literature review of all the studies published about linaclotide up to January 2011. It covers the pharmacodynamics and pharmacokinetics of this novel agent. It also provides a summary of the published clinical trials concerning efficacy and safety in patients with chronic constipation and IBS-C. The authors provide the reader with a better understanding of how the molecular pathophysiology of certain enteropathic diarrheal bacteria lead to the development of this novel prosecretory drug. The reader will also learn about the development of molecularly-based treatment options for chronic constipation and other constipation-associated disorders such as IBS-C. EXPERT OPINION: Linaclotide appears to be a well-tolerated and effective agent for many patients with chronic constipation and IBS-C. Two Phase III studies in chronic constipation and two in IBS-C have provided promising data on the efficacy and safety of this agent for these two disorders. The positioning of linaclotide among the various available agents for these two disorders remains to be established after approval from the FDA is granted.

10 years of capsule endoscopy: an update.

Capsule endoscopy (CE) has evolved in a few short years to become a first-line, noninvasive diagnostic technique for the small bowel. CE is now being utilized worldwide to assess patients for obscure gastrointestinal bleeding, possible Crohn's disease, celiac disease and small bowel tumors. The device is now used in tandem with balloon enteroscopy to direct therapeutic interventions. Alterations and improvements in CE have also led to the evaluation of both the esophagus and colon. It can be anticipated that in the near future pan CE of the entire GI tract will be performed, as well as possible tissue acquisition, drug delivery and therapeutic interventions.

Liver disease in pregnancy.

Liver diseases in pregnancy may be categorized into liver disorders that occur only in the setting of pregnancy and liver diseases that occur coincidentally with pregnancy. Hyperemesis gravidarum, preeclampsia/eclampsia, syndrome of hemolysis, elevated liver tests and low platelets (HELLP), acute fatty liver of pregnancy, and intrahepatic cholestasis of pregnancy are pregnancy-specific disorders that may cause elevations in liver tests and hepatic dysfunction. Chronic liver diseases, including cholestatic liver disease, autoimmune hepatitis, Wilson disease, and viral hepatitis may also be seen in pregnancy. Management of liver disease in pregnancy requires collaboration between obstetricians and gastroenterologists/hepatologists. Treatment of pregnancy-specific liver disorders usually involves delivery of the fetus and supportive care, whereas management of chronic liver disease in pregnancy is directed toward optimizing control of the liver disorder. Cirrhosis in the setting of pregnancy is less commonly observed but offers unique challenges for patients and practitioners. This article reviews the epidemiology, pathophysiology, diagnosis, and management of liver diseases seen in pregnancy.

Role of cortisol in menstrual recovery in adolescent girls with anorexia nervosa.

Neuroendocrine abnormalities in anorexia nervosa (AN) include hypercortisolemia, hypogonadism, and hypoleptinemia, and neuroendocrine predictors of menstrual recovery are unclear. Preliminary data suggest that increases in fat mass may better predict menstrual recovery than leptin. High doses of cortisol decrease luteinizing hormone (LH) pulse frequency, and cortisol predicts regional fat distribution. We hypothesized that an increase in fat mass and decrease in cortisol would predict menstrual recovery in adolescents with AN. Thirty-three AN girls 12-18 y old and 33 controls were studied prospectively for 1 y. Body composition [dual energy x-ray absorptiometry (DXA)], leptin, and urinary cortisol (UFC) were measured at 0, 6, and 12 mo. Serum cortisol was measured overnight (every 30 min) in 18 AN subjects and 17 controls. AN subjects had higher UFC/cr x m2 and cortisol area under curve (AUC), and lower leptin levels than controls. Leptin increased significantly with recovery. When menses-recovered AN subjects were compared with AN subjects not recovering menses and controls, menses-recovered AN subjects had higher baseline cortisol levels and greater increases in leptin than controls and greater increases in fat mass than AN subjects not recovering menses and controls (adjusted for multiple comparisons). In a logistic regression model, increasing fat mass, but not leptin, predicted menstrual recovery. Baseline cortisol level strongly predicted increases in the percentage of body fat. We demonstrate that 1) high baseline cortisol level predicts increases in body fat and 2) increases in body fat predict menses recovery in AN.

Elevated peptide YY levels in adolescent girls with anorexia nervosa.

BACKGROUND: Peptide YY (PYY) is an intestinally derived anorexigen that acts via the Y2 receptor, and Y2 receptor deletion in rodents increases bone formation. Anorexia nervosa (AN) is associated with a deliberate reduction in food intake and low bone density, but endocrine modulators of food intake in AN are not known. In addition, known regulators of bone turnover, such as GH, cortisol, and estrogen, explain only a fraction of the variability in bone turnover marker levels. HYPOTHESES: We hypothesized that PYY may be elevated in AN compared with controls and may contribute to decreased food intake and bone formation. METHODS: Fasting PYY was examined in 23 AN girls and 21 healthy adolescents 12-18 yr old. We also examined GH, cortisol, ghrelin, and leptin (overnight frequent sampling) and fasting IGF-I, estradiol, total T3, and bone markers. Macronutrient intake and resting energy expenditure (REE) were measured. RESULTS: AN girls had higher PYY levels compared with controls (17.8 +/- 10.2 vs. 4.8 +/- 4.3 pg/ml; P < 0.0001). Predictors of log PYY were nutritional markers, including body mass index (r = -0.62; P < 0.0001), fat mass (r = -0.55; P = 0.0003), and REE (r = -0.51; P = 0.0006), and hormones, including GH (r = 0.38; P = 0.004) and T3 (r = -0.59; P = 0.0001). Body mass index, fat mass, REE, GH, and T3 explained 68% of the variability of log PYY. Log PYY predicted percentage of calories from fat (r = -0.56; P = 0.0002) and independently predicted osteocalcin (r = -0.45; P = 0.003), bone-specific alkaline phosphatase (r = -0.46; P = 0.003), N-telopeptide/creatinine (r = -0.55; P = 0.0003), and deoxypyridinoline/creatinine (r = -0.52; P = 0.001) on regression modeling. CONCLUSION: Elevated PYY may contribute to reduced intake and decreased bone turnover in AN.