Epigenetic Impact of Curcumin and Thymoquinone on Cancer Therapeutics.

Today, one of the most prevalent reasons for death among people is carcinoma. Because it is still on the increase throughout the world, there is a critical need for in- -depth research on the pathogenic mechanisms behind the disease as well as for efficient treatment. In the field of epigenetics, gene expression alterations that are inherited but not DNA sequence changes are investigated. Three key epigenetic changes, histone modifications, DNA methylation and non-coding RNA (ncRNA) expression, are principally responsible for the initiation and progression of different tumors. These changes are interconnected and constitute many epigenetic changes. A form of polyphenolic chemical obtained from plants called curcumin has great bioactivity against several diseases, specifically cancer. A naturally occurring substance called thymoquinone is well-known for its anticancer properties. Thymoquinone affects cancer cells through a variety of methods, according to preclinical studies. We retrieved information from popular databases, including PubMed, Google Scholar, and CNKI, to summarize current advancements in the efficiency of curcumin against cancer and its epigenetic regulation in terms of DNA methylation, histone modifications, and miRNA expression. The present investigation offers thorough insights into the molecular processes, based on epigenetic control, that underlie the clinical use of curcumin and thymoquinone in cancerous cells.

Functional filter for whole-genome sequencing data identifies HHT and stress-associated non-coding SMAD4 polyadenylation site variants >5 kb from coding DNA.

Despite whole-genome sequencing (WGS), many cases of single-gene disorders remain unsolved, impeding diagnosis and preventative care for people whose disease-causing variants escape detection. Since early WGS data analytic steps prioritize protein-coding sequences, to simultaneously prioritize variants in non-coding regions rich in transcribed and critical regulatory sequences, we developed GROFFFY, an analytic tool that integrates coordinates for regions with experimental evidence of functionality. Applied to WGS data from solved and unsolved hereditary hemorrhagic telangiectasia (HHT) recruits to the 100,000 Genomes Project, GROFFFY-based filtration reduced the mean number of variants/DNA from 4,867,167 to 21,486, without deleting disease-causal variants. In three unsolved cases (two related), GROFFFY identified ultra-rare deletions within the 3' untranslated region (UTR) of the tumor suppressor SMAD4, where germline loss-of-function alleles cause combined HHT and colonic polyposis (MIM: 175050). Sited >5.4 kb distal to coding DNA, the deletions did not modify or generate microRNA binding sites, but instead disrupted the sequence context of the final cleavage and polyadenylation site necessary for protein production: By iFoldRNA, an AAUAAA-adjacent 16-nucleotide deletion brought the cleavage site into inaccessible neighboring secondary structures, while a 4-nucleotide deletion unfolded the downstream RNA polymerase II roadblock. SMAD4 RNA expression differed to control-derived RNA from resting and cycloheximide-stressed peripheral blood mononuclear cells. Patterns predicted the mutational site for an unrelated HHT/polyposis-affected individual, where a complex insertion was subsequently identified. In conclusion, we describe a functional rare variant type that impacts regulatory systems based on RNA polyadenylation. Extension of coding sequence-focused gene panels is required to capture these variants.

Scope of Wnt signaling in the precise diagnosis and treatment of breast cancer.

Malignant breast cancers are responsible for a growing number of deaths among women globally. The latest research has demonstrated that Wnt signaling is pivotal in this disease, regulating a safe microenvironment for the growth and proliferation of cancer cells, sustained stemness, resistance to therapy, and aggregate formation. The three highly conserved Wnt signaling pathways, Wnt-planar cell polarity (PCP), Wnt/ß-catenin signaling and Wnt-Ca2+ signaling, assume various roles in the maintenance and amelioration of breast cancer. In this review, we examine ongoing studies on the Wnt signaling pathways and discuss how dysregulation of these pathways promotes breast cancers. We also look at how Wnt dysregulation could be exploited to foster new treatments for malignant breast cancers.

Cost-effectiveness of cenobamate for focal seizures in people with drug-resistant epilepsy.

OBJECTIVE: This study was undertaken to estimate the cost-effectiveness of add-on cenobamate in the UK when used to treat drug-resistant focal seizures in adults who are not adequately controlled with at least two prior antiseizure medications, including at least one used adjunctively. METHODS: We estimated the cost per quality-adjusted life-year (QALY) for cenobamate compared to brivaracetam, eslicarbazepine, lacosamide, and perampanel in the UK National Health Service over a lifetime time horizon. We used a Markov cohort structure to determine response to treatment, using pooled data from three long-term studies of cenobamate. A network meta-analysis informed the likelihood of response to therapy with brivaracetam, eslicarbazepine, lacosamide, and perampanel relative to cenobamate. Once individuals discontinued treatment, they transitioned to subsequent treatment health states, including other antiseizure medicines, surgery, and vagus nerve stimulation. Costs included treatment, administration, routine monitoring, event management, and adverse events. Published evidence and expert opinion informed the likelihood of response to subsequent treatments, associated adverse events, and costs. Utility data were based on Short-Form six-dimension form utility. Discounting was applied at 3.5% per annum as per National Institute for Health and Care Excellence guidance. Uncertainty was explored through deterministic and probabilistic sensitivity analyses. RESULTS: In the base case, cenobamate led to cost savings of £51 967 (compared to brivaracetam), £21 080 (compared to eslicarbazepine), £33 619 (compared to lacosamide), and £28 296 (compared to perampanel) and increased QALYs of 1.047 (compared to brivaracetam), 0.598 (compared to eslicarbazepine), 0.776 (compared to lacosamide), and 0.703 (compared to perampanel) per individual over a lifetime time horizon. Cenobamate also dominated the four drugs across most sensitivity analyses. Differences were due to reduced seizure frequency with cenobamate relative to comparators. SIGNIFICANCE: Cenobamate improved QALYs and was less costly than brivaracetam, eslicarbazepine, lacosamide, and perampanel. Therefore, cenobamate may be considered as a cost-effective adjunctive antiseizure medication for people with drug-resistant focal seizures.

Psychosocial aspects of sports medicine in pediatric athletes: Current concepts in the 21st century.

Behavioral aspects of organized sports activity for pediatric athletes are considered in a world consumed with winning at all costs. In the first part of this treatise, we deal with a number of themes faced by our children in their sports play. These concepts include the lure of sports, sports attrition, the mental health of pediatric athletes (i.e., effects of stress, anxiety, depression, suicide in athletes, ADHD and stimulants, coping with injuries, drug use, and eating disorders), violence in sports (i.e., concepts of the abused athlete including sexual abuse), dealing with supervisors (i.e., coaches, parents), peers, the talented athlete, early sports specialization and sports clubs. In the second part of this discussion, we cover ergolytic agents consumed by young athletes in attempts to win at all costs. Sports doping agents covered include anabolic steroids (anabolic-androgenic steroids or AAS), androstenedione, dehydroepiandrostenedione (DHEA), human growth hormone (hGH; also its human recombinant homologue: rhGH), clenbuterol, creatine, gamma hydroxybutyrate (GHB), amphetamines, caffeine and ephedrine. Also considered are blood doping that includes erythropoietin (EPO) and concepts of gene doping. In the last section of this discussion, we look at disabled pediatric athletes that include such concepts as athletes with spinal cord injuries (SCIs), myelomeningocele, cerebral palsy, wheelchair athletes, and amputee athletes; also covered are pediatric athletes with visual impairment, deafness, and those with intellectual disability including Down syndrome. In addition, concepts of autonomic dysreflexia, boosting and atlantoaxial instability are emphasized. We conclude that clinicians and society should protect our precious pediatric athletes who face many challenges in their involvement with organized sports in a world obsessed with winning. There is much we can do to help our young athletes find benefit from sports play while avoiding or blunting negative consequences of organized sport activities.

The formaldehyde treated guar meal and prill fat, agro industrial by-products as dietary rumen protected protein and energy source: improves growth performance, feed conversion, nutrient utilization, microbial protein synthesis, blood metabolites and economic efficiency in growing dairy buffalo (Bubalus bubalis) calves.

The study investigated the effects of protein replacement with formaldehyde-treated guar meal (FTGM) and prill fat (PF) in the diet on performance of growing dairy buffalo calves. Thirty-two feedlots Surti breed dairy buffalo calves (age, 7.31 ± 0.34 months and body weight, 90.69 ± 6.19 kg) were assigned into four dietary treatments (n-8 calves/each): (1) control group, supplied basal diet as per ICAR (2013) nutrient requirements; (2) FTGM group, 30% crude protein (CP) requirement of concentrate mixture (dry matter basis (DMB)) replaced with FTGM in basal diet; (3) PF group, supplied basal diet + 100 g PF; and (4) FTGM + PF group, 30% CP requirement of concentrate mixture (DMB) replaced with FTGM in the basal diet + 100 g PF for 280 days. All the treatment diets were isonitrogenous. Growth performance was improved in FTGM + PF and FTGM groups. Apparent digestibility (%) of CP was increased in FTGM and FTGM + PF diet, while digestibility (%) of ether extract (EE) was increased in PF group. Serum total protein, albumen, urea nitrogen, and creatinine concentrations were higher in FTGM + PF and FTGM groups, whereas total cholesterol and triglycerides levels were greater in FTGM + PF and PF groups. Calculated methane emission had a discernible influence of treatment in FTGM and FTGM + PF. The overall cost of feeding per kilogram gain was lowest in FTGM and FTGM + PF groups. In conclusion, 30% CP replacement with FTGM with or without PF improved the growth performance, feed conversion ratio, and nutrient utilization; supported efficient utilization of resources; and economized the rearing of growing dairy buffalo calves.

Quantitative magnetic resonance imaging predicts individual future liver performance after liver resection for cancer.

The risk of poor post-operative outcome and the benefits of surgical resection as a curative therapy require careful assessment by the clinical care team for patients with primary and secondary liver cancer. Advances in surgical techniques have improved patient outcomes but identifying which individual patients are at greatest risk of poor post-operative liver performance remains a challenge. Here we report results from a multicentre observational clinical trial (ClinicalTrials.gov NCT03213314) which aimed to inform personalised pre-operative risk assessment in liver cancer surgery by evaluating liver health using quantitative multiparametric magnetic resonance imaging (MRI). We combined estimation of future liver remnant (FLR) volume with corrected T1 (cT1) of the liver parenchyma as a representation of liver health in 143 patients prior to treatment. Patients with an elevated preoperative liver cT1, indicative of fibroinflammation, had a longer post-operative hospital stay compared to those with a cT1 within the normal range (6.5 vs 5 days; p = 0.0053). A composite score combining FLR and cT1 predicted poor liver performance in the 5 days immediately following surgery (AUROC = 0.78). Furthermore, this composite score correlated with the regenerative performance of the liver in the 3 months following resection. This study highlights the utility of quantitative MRI for identifying patients at increased risk of poor post-operative liver performance and a longer stay in hospital. This approach has the potential to inform the assessment of individualised patient risk as part of the clinical decision-making process for liver cancer surgery.

Presentation, diagnostic assessment and surgical outcomes in primary hyperparathyroidism: a single centre's experience.

OBJECTIVE: Primary hyperparathyroidism (PHPT) is a common reason for referral to endocrinology but the evidence base guiding assessment is limited. We evaluated the clinical presentation, assessment and subsequent management in PHPT. DESIGN: Retrospective cohort study. PATIENTS: PHPT assessed between 2006 - 2014 (n = 611) in a university hospital. MEASUREMENTS: Symptoms, clinical features, biochemistry, neck radiology and surgical outcomes. RESULTS: Fatigue (23.8%), polyuria (15.6%) and polydipsia (14.9%) were associated with PHPT biochemistry. Bone fracture was present in 16.4% but was not associated with biochemistry. A history of nephrolithiasis (10.0%) was associated only with younger age (P = 0.006) and male gender (P = 0.037). Thiazide diuretic discontinuation was not associated with any subsequent change in calcium (P = 0.514). Urine calcium creatinine clearance ratio (CCCR) was <0.01 in 18.2% of patients with confirmed PHPT. Older age (P < 0.001) and lower PTH (P = 0.043) were associated with failure to locate an adenoma on ultrasound (44.0% of scans). When an adenoma was identified on ultrasound the lateralization was correct in 94.5%. Non-curative surgery occurred in 8.2% and was greater in those requiring more than one neck imaging modality (OR 2.42, P = 0.035). CONCLUSIONS: Clinical features associated with PHPT are not strongly related to biochemistry. Thiazide cessation does not appear to attenuate hypercalcaemia. PHPT remains the likeliest diagnosis in the presence of low CCCR. Ultrasound is highly discriminant when an adenoma is identified but surgical failure is more likely when more than one imaging modality is required.

Pediatric obesity: Current concepts.

This discussion reflects on concepts of obesity in children and adolescents in the early 21st century. It includes reflections on its history, definition, epidemiology, diagnostic perspectives, psychosocial considerations, musculoskeletal complications, endocrine complications and principles of management. In addition to emphasis on diet and exercise, research and clinical applications in the second decade of the 21st century emphasize the increasing use of pharmacotherapy and bariatric surgery for adolescent and adult populations with critical problems of overweight and obesity. We conclude with a discussion of future directions in pediatric obesity management.

The BRICS (Bronchiectasis Radiologically Indexed CT Score): A Multicenter Study Score for Use in Idiopathic and Postinfective Bronchiectasis.

OBJECTIVES: The goal of this study was to develop a simplified radiological score that could assess clinical disease severity in bronchiectasis. METHODS: The Bronchiectasis Radiologically Indexed CT Score (BRICS) was devised based on a multivariable analysis of the Bhalla score and its ability in predicting clinical parameters of severity. The score was then externally validated in six centers in 302 patients. RESULTS: A total of 184 high-resolution CT scans were scored for the validation cohort. In a multiple logistic regression model, disease severity markers significantly associated with the Bhalla score were percent predicted FEV1, sputum purulence, and exacerbations requiring hospital admission. Components of the Bhalla score that were significantly associated with the disease severity markers were bronchial dilatation and number of bronchopulmonary segments with emphysema. The BRICS was developed with these two parameters. The receiver operating-characteristic curve values for BRICS in the derivation cohort were 0.79 for percent predicted FEV1, 0.71 for sputum purulence, and 0.75 for hospital admissions per year; these values were 0.81, 0.70, and 0.70, respectively, in the validation cohort. Sputum free neutrophil elastase activity was significantly elevated in the group with emphysema on CT imaging. CONCLUSIONS: A simplified CT scoring system can be used as an adjunct to clinical parameters to predict disease severity in patients with idiopathic and postinfective bronchiectasis.

Multidetector Computed Tomography Versus Staging Laparoscopy for the Detection of Peritoneal Metastases in Esophagogastric Junctional and Gastric Cancer.

OBJECTIVE: Staging laparoscopy (SL) is the gold standard investigation for detecting peritoneal metastases (PM) in patients with esophagogastric cancer but computed tomography (CT) has undergone significant improvements in recent years. The aim of this study was to investigate whether CT can replace SL in the detection of PM. MATERIALS AND METHODS: Patients undergoing SL between January 2008 and December 2009 were identified from a prospectively collected database, operation notes were reviewed for the detection of PM. Corresponding CTs were reassessed by 2 experienced gastrointestinal radiologists, blinded to the SL results. RESULTS: In total, 74 patients undergoing SL were included. Sensitivity and specificity of SL for PM were 94.1% (95% confidence interval, 69.2-99.7) and 100% (90.7-100). Sensitivity and specificity of CT were 58.8% (33.5-80.6) and 89.6% (76.6-96.1), respectively. Area under the curve of receiver operating characteristic curves for SL and CT were 0.971 (SE, 0.033) and 0.742 (SE, 0.78), respectively. CONCLUSIONS: CT cannot replace SL for the detection of PM in lower esophageal and gastric cancer.

Computed tomography myocardial perfusion vs 15O-water positron emission tomography and fractional flow reserve.

OBJECTIVES: Computed tomography (CT) can perform comprehensive cardiac imaging. We compared CT coronary angiography (CTCA) and CT myocardial perfusion (CTP) with 15O-water positron emission tomography (PET) and invasive coronary angiography (ICA) with fractional flow reserve (FFR). METHODS: 51 patients (63 (61-65) years, 80 % male) with known/suspected coronary artery disease (CAD) underwent 320-multidetector CTCA followed by "snapshot" adenosine stress CTP. Of these 22 underwent PET and 47 ICA/FFR. Obstructive CAD was defined as CTCA stenosis >50 % and CTP hypoperfusion, ICA stenosis >70 % or FFR <0.80. RESULTS: PET hyperaemic myocardial blood flow (MBF) was lower in obstructive than non-obstructive territories defined by ICA/FFR (1.76 (1.32-2.20) vs 3.11 (2.44-3.79) mL/(g/min), P < 0.001) and CTCA/CTP (1.76 (1.32-2.20) vs 3.12 (2.44-3.79) mL/(g/min), P < 0.001). Baseline and hyperaemic CT attenuation density was lower in obstructive than non-obstructive territories (73 (71-76) vs 86 (84-88) HU, P < 0.001 and 101 (96-106) vs 111 (107-114) HU, P 0.001). PET hyperaemic MBF corrected for rate pressure product correlated with CT attenuation density (r = 0.579, P < 0.001). There was excellent per-patient sensitivity (96 %), specificity (85 %), negative predictive value (90 %) and positive predictive value (94 %) for CTCA/CTP vs ICA/FFR. CONCLUSION: CT myocardial attenuation density correlates with 15O-water PET MBF. CTCA and CTP can accurately identify obstructive CAD. KEY POINTS: •CT myocardial perfusion can aid the assessment of suspected coronary artery disease. • CT attenuation density from "snapshot" imaging is a marker of myocardial perfusion. • CT myocardial attenuation density correlates with 15 O-water PET myocardial blood flow. • CT attenuation density is lower in obstructive territories defined by invasive angiography. • Diagnostic accuracy of CTCA+CTP is comparable to invasive angiography + fractional flow reserve.

Can Iron Treatments Aggravate Epistaxis in Some Patients With Hereditary Hemorrhagic Telangiectasia?

OBJECTIVES/HYPOTHESIS: To examine whether there is a rationale for iron treatments precipitating nosebleeds (epistaxis) in a subgroup of patients with hereditary hemorrhagic telangiectasia (HHT). STUDY DESIGN: Survey evaluation of HHT patients, and a randomized control trial in healthy volunteers. METHODS: Nosebleed severity in response to iron treatments and standard investigations were evaluated by unbiased surveys in patients with HHT. Serial blood samples from a randomized controlled trial of 18 healthy volunteers were used to examine responses to a single iron tablet (ferrous sulfate, 200 mg). RESULTS: Iron tablet users were more likely to have daily nosebleeds than non-iron-users as adults, but there was no difference in the proportions reporting childhood or trauma-induced nosebleeds. Although iron and blood transfusions were commonly reported to improve nosebleeds, 35 of 732 (4.8%) iron tablet users, in addition to 17 of 261 (6.5%) iron infusion users, reported that their nosebleeds were exacerbated by the respective treatments. These rates were significantly higher than those reported for control investigations. Serum iron rose sharply in four of the volunteers ingesting ferrous sulfate (by 19.3-33.1 µmol/L in 2 hours), but not in 12 dietary controls (2-hour iron increment ranged from -2.2 to +5.0 µmol/L). High iron absorbers demonstrated greater increments in serum ferritin at 48 hours, but transient rises in circulating endothelial cells, an accepted marker of endothelial damage. CONCLUSIONS: Iron supplementation is essential to treat or prevent iron deficiency, particularly in patients with pathological hemorrhagic iron losses. However, in a small subgroup of individuals, rapid changes in serum iron may provoke endothelial changes and hemorrhage. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2468-2474, 2016.

The Cost-effectiveness of Pixantrone for Third/Fourth-line Treatment of Aggressive Non-Hodgkin's Lymphoma.

PURPOSE: Aggressive non-Hodgkin's lymphoma (aNHL) is associated with poor long-term survival after relapse, and treatment is limited by a lack of consensus regarding standard of care. Pixantrone was studied in a randomized trial in patients with relapsed or refractory aNHL who had failed ≥ 2 lines of therapy, demonstrating a significant improvement in complete or unconfirmed complete response and progression-free survival (PFS) compared with investigators' choice of single-agent therapy. The objective of this study was to assess the health economic implications of pixantrone versus current clinical practice (CCP) in the United Kingdom for patients with multiply relapsed or refractory aNHL receiving their third or fourth line of treatment. METHODS: A semi-Markov partition model based on overall survival and PFS was developed to evaluate the lifetime clinical and economic impact of treatment of multiply relapsed or refractory aNHL with pixantrone versus CCP. The empirical overall survival and PFS data from the PIX301 trial were extrapolated to a lifetime horizon. Resource use was elicited from clinical experts, and unit costs and utilities were obtained from published sources. The analysis was conducted from the perspective of the United Kingdom's National Health Service and personal social services. Outcomes evaluated were total costs, life-years, quality-adjusted life-years (QALYs), and cost per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty around the results. FINDINGS: Pixantrone was estimated to increase life expectancy by a mean of 10.8 months per patient compared with CCP and a mean gain of 0.56 discounted QALYs. The increased health gains were associated with an increase in discounted costs of approximately £18,494 per patient. The incremental cost-effectiveness ratio of pixantrone versus CCP was £33,272 per QALY gained. Sensitivity and scenario analyses suggest that the incremental cost-effectiveness ratio was sensitive to uncertainty in the PFS and overall survival estimates and the utility values associated with each health state. IMPLICATIONS: Pixantrone may be considered both clinically effective and cost-effective for patients with multiply relapsed or refractory aNHL who currently have a high level of unmet need.

Low and fixed dose of hydroxyurea is effective and safe in patients with HbSß(+) thalassemia with IVS1-5(G→C) mutation.

BACKGROUND: Despite compelling evidence that hydroxyurea is safe and effective in sickle cell disease, it is prescribed sparingly due to several barriers like knowledge gaps in certain genotypes, apprehension about its safety and toxicity, and limited resources. We undertook this study to find out the efficacy and safety of HU in patients with HbSß(+) -thalassemia with IVS1-5(G→C) mutation. PROCEDURE: We registered 318 patients with HbSß(+) -thalassemia with IVS1-5(G→C) mutation. Of these, 203 were enrolled for hydroxyurea treatment at a low and fixed dose of 10 mg/kg/day. One hundred four patients (Group-I: 37 children and Group-II: 67 adults) with ≥2 years of hydroxyurea treatment were studied. RESULTS: The rate of vaso-occlusive crises, requirement of blood transfusion and rate of hospitalization reduced from 3 to 0.5, 1 to 0 and 1 to 0 in Group-I and 3 to 0, 1 to 0 and 0.5 to 0 in Group-II respectively after HU therapy (P < 0.0001). %HbF level, hemoglobin, MCV and MCH increased significantly, whereas HbS, WBC, platelet count, serum-bilirubin and LDH levels decreased significantly after HU therapy. It has been observed that along with fairly subtle hematological changes following HU therapy, there was a substantial clinical improvement occurred in these patients. Transient myelotoxicity was observed in 4.8%. There was minimal gonadal toxicity without affecting reproductive function. CONCLUSION: In view of easy affordability, better acceptability, minimal toxicity, the need of infrequent monitoring and its potential effectiveness, low and fixed dose of hydroxyurea is suitable for treatment of patients with HbSß(+) -thalassemia in resource poor setting.

The effect of hydroxyurea on compound heterozygotes for sickle cell-hemoglobin D-Punjab--a single centre experience in eastern India.

BACKGROUND: Although hydroxyurea is the only effective agent for the treatment of sickle cell disease, published experience with this drug is limited to treatment of homozygous sickle cell anemia and HbS/ß thalassemia. The role of hydroxyurea in the treatment of patients with HbSD-Punjab, a rare hemoglobinopathy with phenotypic expression similar to that of sickle cell anemia is unknown. PROCEDURE: Over a period of 10 years, we followed 42 patients with HbSD-Punjab, of which 20 presented with severe clinical manifestations (≥3 episodes of VOC and/or ≥2 units of blood transfusion in the previous 12 months). These 20 patients were enrolled for treatment with hydroxyurea at a dose of 10 mg/kg/day and followed prospectively for a period of 24 months. RESULTS: The frequency of VOC decreased significantly and none of them required blood transfusion while receiving hydroxyurea. The HbF, total hemoglobin, MCV, MCH, and MCHC levels increased significantly, whereas HbS, WBC, platelet count, total serum bilirubin, and LDH levels decreased significantly in all the patients. No short-term drug toxicity was observed. CONCLUSION: This study describes the use of hydroxyurea therapy in patients with HbSD-Punjab. Low dose hydroxyurea (10 mg/kg/day) was found to be effective in reducing the clinical severity in patients with HbSD-Punjab without any short-term toxicity. In view of easy affordability amongst poor patients, widespread acceptability by patients and doctors, the need of infrequent monitoring and its potential effectiveness, low dose hydroxyurea is suitable for treatment of patients with HbSD-Punjab.

Computed tomography angiography in the diagnosis of ANCA-associated small- and medium-vessel vasculitis.

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis that typically occurs without detectable antineutrophil cytoplasmic antibody. It leads to aneurysm formation by affecting muscular arteries, usually those of medium size but also occasionally those of small size. Kidney involvement is common, leading to reduced glomerular filtration rate, hypertension, rupture of renal arterial aneurysms causing perinephric hematomas, and renal infarctions in those with severe vasculitis. Similar to PAN, microscopic polyangiitis (MPA) leads to aneurysm formation; however, MPA usually is associated with antineutrophil cytoplasmic antibody, and glomerulonephritis is a more common feature of MPA. Although kidney biopsy may show classic vascular changes in both PAN and MPA, this procedure is not without risk of significant bleeding due to aneurysm rupture. We present 2 cases of renal aneurysms that were diagnosed as MPA using computed tomography angiography (CTA), allowing implementation of appropriate immunosuppressive therapy. Follow-up CTA after treatment showed resolution of all previously observed abnormalities. CTA is a useful alternative to kidney biopsy in establishing both the extent of disease in renal aneurysms and allowing for tracking of disease progression and response to therapy.

Parental beliefs and knowledge about male human papillomavirus vaccination in the US: a survey of a pediatric clinic population.

The purpose of this study is to examine US parental knowledge of human papillomavirus (HPV) in males, views on vaccination, and correlation to vaccination rates. The survey was conducted of clinic population about parental knowledge and beliefs of male HPV health outcomes and vaccination. There were a total of 102 participants who completed the survey. Perceived parental knowledge about the virus was reported as "a lot" by 11%, "some" by 50%, and "very little/nothing" by 38% of the participants. However, knowledge of HPV was moderate, with only 14% of the respondents answering all knowledge questions correctly; 64% of the respondents correctly identified HPV as a cause of genital warts in males, 43% identified at least one HPV-related cancer, and 30% were unable to identify any health outcomes in males. There was a statistically significant correlation between perceived and actual knowledge, with >15% of the survey respondents correctly identifying that HPV does not clear up on its own (p=0.004). Of the participants who did not vaccinate, reasons included the following: 54% fulfilled the child's wish not to be vaccinated, 38% reported belief vaccine is unsafe, and 38% indicated that their children are too young and/or expressed fear that the vaccine would negatively affect behavior. This study supports the fact that parental beliefs and attitudes are more important than actual knowledge about HPV or HPV vaccination. The implication to physicians is to tailor discussions to address fears about the dangers or complications, emphasize the safety of the vaccine, and address sources of misinformation.

A rare case of factor V inhibitor in a patient on amiodarone therapy.

Factor V inhibitor is in itself a rare entity. We are reporting a case of an elderly male who presented with symptoms of bleeding and was later found to have developed factor V inhibitors. He had been on amiodarone for atrial fibrillation and developed hemorrhagic manifestations due to factor V inhibitors within a few months of initiating amiodarone therapy. Most of the cases of factor V inhibitors reported in the literature were found to be associated with exposure to bovine coagulation factors. However, in our case there was no evidence of bovine thrombin use during surgery. Furthermore, bovine thrombin-associated factor V inhibitors commonly emerge within 1-2 weeks after exposure during surgery versus several months later in our patient. There was dramatic improvement in the coagulation profile 6 weeks after discontinuation of amiodarone and institution of steroids and cyclophosphamide. We propose the consideration of amiodarone as a contributing agent in inhibitor generation even though a spontaneous development of factor V inhibitor could not be ruled out.