Phillips, Michael

The following describes a case of isolated visceral angioedema related to an angiotensin II receptor blocker (ARB) medication. Additionally, we discuss the pathophysiology of drug-induced angioedema, various presentations that can be encountered, and the leading theorized mechanisms of how renin-angiotensin-aldosterone system (RAAS) blocking medications lead to angioedema. The goal of sharing this case is to help increase awareness of the possibility of ARB-induced angioedema and to recommend keeping visceral angioedema as part of the differential diagnosis when presented with a patient who is taking an angiotensin converting enzyme inhibitor (ACEI) or ARB medication that is experiencing gastrointestinal symptoms of unclear etiology.

Gynecomastia is benign enlargement of glandular tissue in the male breast. It occurs due to an imbalance of estrogen and testosterone. It may be unilateral or bilateral. Physiologic gynecomastia commonly occurs in infants and during puberty and is self-limited. Gynecomastia may affect up to 50% of adult men over age 50 years old and can be related to underlying medical illness or caused by certain medications. Known causative agents include anti-androgenic and estrogenic drugs. Probable agents include alcohol and anti-ulcer, psychoactive, and antiretroviral medications. Non-steroidal anti-inflammatory drugs (NSAIDs) are not commonly associated with the development of gynecomastia. This case presents an instance in which the NSAID, meloxicam, was the only identified variable in a patient who developed unilateral gynecomastia. His breast tenderness and abnormal exam resolved spontaneously within 4 weeks of cessation of meloxicam therapy.

Background While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. Methods In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. Results GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. Conclusions GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.

Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. Methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.

Background The epidemiological transition of non-communicable diseases replacing infectious diseases as the main contributors to disease burden has been well documented in global health literature. Less focus, however, has been given to the relationship between sociodemographic changes and injury. The aim of this study was to examine the association between disability-adjusted life years (DALYs) from injury for 195 countries and territories at different levels along the development spectrum between 1990 and 2017 based on the Global Burden of Disease (GBD) 2017 estimates. Methods Injury mortality was estimated using the GBD mortality database, corrections for garbage coding and CODEm—the cause of death ensemble modelling tool. Morbidity estimation was based on surveys and inpatient and outpatient data sets for 30 cause-of-injury with 47 nature-of-injury categories each. The Socio-demographic Index (SDI) is a composite indicator that includes lagged income per capita, average educational attainment over age 15 years and total fertility rate. Results For many causes of injury, age-standardised DALY rates declined with increasing SDI, although road injury, interpersonal violence and self-harm did not follow this pattern. Particularly for self-harm opposing patterns were observed in regions with similar SDI levels. For road injuries, this effect was less pronounced. Conclusions The overall global pattern is that of declining injury burden with increasing SDI. However, not all injuries follow this pattern, which suggests multiple underlying mechanisms influencing injury DALYs. There is a need for a detailed understanding of these patterns to help to inform national and global efforts to address injury-related health outcomes across the development spectrum.

Smoking is a major risk factor for failure of coronary artery bypass grafts (CABG). Experiments were designed to determine effects of transdermal nicotine, independent of smoking, on structure and function of CABG. Saphenous veins were placed as CABG in untreated dogs (control) or in dogs treated with transdermal nicotine (one 11-mg or two 22-mg patches/day) for 5 wk. Serum nicotine and plasma nitric oxide were measured. Grafts were removed and prepared for organ chamber studies and histology. Serum nicotine averaged 12.1 and 118.7 ng/ml in the 11 mg/day and 44 mg/day groups, respectively. Plasma nitric oxide was higher in dogs treated with 11 mg/day doses compared with controls. In organ chamber studies, endothelium-dependent relaxations to thrombin and A-23187 and endothelium-independent relaxations to nitric oxide were greatest in grafts from dogs treated with 11 mg/day doses. Intimal thickness of the grafts were similar among groups. However, staining for bone sialoprotein was increased in the media of grafts from the 11 mg/day treatment group. These data suggest that transdermal nicotine in doses comparable and double to those used for conventional smoking cessation treatment in humans does not adversely affect early patency of canine CABG up to 4 wk postoperatively. Transdermal nicotine, however, may increase production of and response to nitric oxide in bypass grafts.

Select subsets of patients require prosthetic graft material for revascularization. Although arterial prosthetic grafts of large caliber perform acceptably, grafts of <6 mm exhibit a high attrition rate. Microvessel endothelial sodding, a method resulting in the lining of prosthetic grafts with autologous endothelium, improves graft patency; however, aggressive antiplatelet therapy is still required, because terminating an antiplatelet regimen accelerates graft attrition. The present investigation was designed to address the acute production of vasoactive substances in microvessel endothelial cell sodded expanded polytetrafluoroethylene (ePTFE) grafts in an attempt to delineate a possible mechanism behind the continued requirement for antiplatelet therapy. Equal lengths of acutely sodded ePTFE grafts (canine falciform ligament source) and saphenous veins (SV) (canine source) were evaluated by superfusion bioassay. Basal secretion from ePTFE grafts relaxed the biodetector ring 1 ± 3%, whereas SV relaxed the ring 10 ± 3% (p < 0.05, ePTFE vs. SV). Relaxation with acetylcholine stimulation was 49 ± 7% in grafts and 50 ± 10% in veins (p = NS). Calcium ionophore stimulation produced relaxation of 37 ± 9% from ePTFE grafts and 100 ± 23% from SV (p < 0.05). Indomethacin added to perfusate reduced relaxations from sodded ePTFE grafts to 20.2 ± 9.2% with acetylcholine stimulation and 12.5 + 4.3% with calcium ionophore (p < 0.05 vs. control); addition of N G -monomethyl-L-arginine (L-NMMA) had no effect on the release of vasoactive substances from ePTFE grafts. In contrast, relaxations of effluent from SV stimulated by acetylcholine and calcium ionophore were significantly attenuated with indomethacin and L-NMMA (p < 0.05 vs. control). Scanning electron microscopy demonstrated confluent endothelium in SV and a nonconfluent endothelial cell layer in grafts. Acutely sodded ePTFE grafts produce vasoactive substances that quantitatively and qualitatively differ from those produced by canine SV. The ePTFE grafts produce mainly prostanoids, whereas SV produce both nitric oxide and prostanoids. The endothelial cell isolation procedure and absence of immediate graft luminal confluence may contribute to the observed differences.

A 47-year-old Hispanic woman developed a chronically obstructed left kidney, due to a long-segment ureteric stricture deemed not amenable to reimplantation, following left ovarian cyst excision in 2004. Therefore, a ureteral stent requiring exchange every 3 months was necessary, due to hydronephrosis, recurrent urosepsis, chronic pain, and a poor quality of life. Her medical history was complicated by hypertension, poorly controlled diabetes mellitus, and microalbuminuria, suggesting early diabetic nephropathy. A left nephrectomy was recommended. This was deferred, due to concern for progressive kidney failure associated with her comorbidities. A radionuclide Tc-99m MAG3 renal scan revealed differential perfusion as follows: 44% left kidney and 56% right kidney, with symmetrical uptake on the renogram phase and delayed excretion on the left, which were correctted following furosemide administration. A left ureteronephrectomy with autotransplantation of the left kidney and ureteroneocystostomy was performed in 2009. Since then, the patient has experienced no further complications or need for invasive procedures, with excellent diabetic control and stable renal function (eGFR > 60 mL/min/1.73 m2). This technique is seldom employed in the surgical management of complex ureteral injuries, but may be an alternative for appropriate cases.