Acute radiation-induced pericarditis complicated by polymicrobial infectious pericarditis in a patient with mediastinal sarcoma: a case report.

Background: Acute pericarditis is often caused by viral infections, autoimmune diseases, and radiation therapy (RT). Infectious pericarditis is rare and associated with high morbidity and mortality. We present a case of acute RT-induced pericarditis complicated by bacterial pericarditis and cardiac tamponade due to oesophageal bacterial translocation. Case summary: A 65-year-old man with a recurrent mediastinal sarcoma complicated by oesophageal compression and recent oesophageal stenting presented with shortness of breath. Electrocardiogram showed diffuse ST elevations, and he was diagnosed with presumed RT-induced pericarditis. Despite anti-inflammatory therapy, he developed haemodynamic instability and clinical tamponade, with transthoracic echocardiogram showing a large circumferential pericardial effusion. He underwent emergent pericardiocentesis, and pericardial fluid cultures grew polymicrobial species. Anti-inflammatories were held, and he was started on broad spectrum intravenous antibiotics and antifungals. Due to clinical decompensation and repeat computed tomography imaging demonstrating worsening pericardial disease, he underwent pericardial irrigation and subxiphoid pericardial window. The patient died from hypoxaemic and hypercapnic respiratory failure. Autopsy revealed constrictive pericarditis and no bacterial organisms in the pericardium. Discussion: Anti-inflammatories are standard treatment for viral and RT-induced pericarditis. Purulent, bacterial pericarditis is rare and an uncommon complication of RT-induced pericarditis. Polymicrobial infectious pericarditis is often refractory to intravenous antibiotics, requiring surgical intervention. This case highlights the importance of maintaining a high index of suspicion of various potential aetiologies of pericarditis in order to tailor medical and surgical therapies especially in high-risk, immunosuppressed cancer patients.

Unraveling Wavy ST Segments-An Unusual Case of Syncope.

This case report describes a patient in their 60s with gastroesophageal reflex disease who presented to the emergency department after loss of consciousness during dinner and daily intermittent chest discomfort.

Outcomes of malignancy in adults with congenital heart disease: a single center experience.

BACKGROUND: Malignancy is known to be a major cause of death in adult congenital heart disease (ACHD). However, data regarding cardiovascular and cancer-related outcomes in ACHD are lacking. METHODS: We conducted a retrospective single-center cohort study comprising patients with ACHD and malignancy. The primary outcome was all-cause mortality. Key secondary outcomes included major adverse cardiovascular and cerebrovascular events (MACCE), cardiotoxicity events and consequent cancer therapy modifications. RESULTS: Sixty-eight patients with ACHD and a history of cancer were included in the study. 82% of patients had moderate or great ACHD anatomic complexity. Over a median follow-up of 5 years after cancer diagnosis, 16 (24%) patients died, with 69% of deaths being due to cancer. Univariate predictors of mortality were baseline arrhythmia (OR 3.82, 95% CI 1.15-12.67, p = 0.028), baseline diuretic therapy (OR 3.54, 95% CI 1.04-12.04, p = 0.044) and advanced cancer stage at diagnosis (OR 2.37, 95% CI 1.32-4.25, p = 0.004). MACCE occurred in 40 (59%) patients and was independently predicted by baseline diuretic requirement (OR 9.91, 95% CI 1.12-87.85, p = 0.039). A 14% incidence of cardiotoxicity was seen; 3 patients needed modification and 1 patient needed temporary interruption of cancer therapy for 2 weeks. CONCLUSIONS: Considerable mortality occurred in this cohort of patients with ACHD and cancer; most deaths were cancer-related. A high rate of MACCE was observed, yet rates of obligatory modification of cancer therapy due to cardiotoxicity were low.

Systems-Level Opportunities in the Management of Primary Hyperparathyroidism: An Informatics-based Assessment.

CONTEXT: Primary hyperparathyroidism (PHPT), a leading cause of hypercalcemia and secondary osteoporosis, is underdiagnosed. OBJECTIVE: This work aims to establish a foundation for an electronic medical record-based intervention that would prompt serum parathyroid hormone (PTH) assessment in patients with persistent hypercalcemia and identify care gaps in their management. METHODS: A retrospective cohort study was conducted in a tertiary academic health system of outpatients with persistent hypercalcemia, who were categorized as having classic or normohormonal PHPT. Main outcome measures included the frequencies of serum PTH measurement in patients with persistent hypercalcemia, and their subsequent workup with bone mineral density (BMD) assessment, and ultimately, medical therapy or parathyroidectomy. RESULTS: Among 3151 patients with persistent hypercalcemia, 1526 (48%) had PTH measured, of whom 1377 (90%) were confirmed to have classic (49%) or normohormonal (41%) PHPT. PTH was measured in 65% of hypercalcemic patients with osteopenia or osteoporosis (P < .001). At median 2-year follow-up, bone density was assessed in 275 (20%) patients with either variant of PHPT (P = .003). Of women aged 50 years or older with classic PHPT, 95 (19%) underwent BMD assessment. Of patients with classic or normohormonal PHPT, 919 patients (67%) met consensus criteria for surgical intervention, though only 143 (15%) underwent parathyroidectomy. CONCLUSION: Within a large academic health system, more than half of patients with confirmed hypercalcemia were not assessed for PHPT, including many patients with preexisting bone disease. Care gaps in BMD assessment and medical or surgical therapy represent missed opportunities to avoid skeletal and other complications of PHPT.

Management of Biliary Stricture in Pediatric Liver Transplantation Patients: Long-Term Outcomes.

Postoperative biliary complications have been reported to occur in 10% to 33% of pediatric liver transplantation (LT) recipients. Percutaneous intervention has become the primary treatment method for these complications; however, the efficacy and outcomes of these patients have not been well studied. Institutional pediatric LT from 1998 to 2019 were retrospectively reviewed to determine the patients referred for percutaneous treatment of post-LT biliary strictures. Clinical parameters, percutaneous transhepatic cholangiograms (PTCs), biliary catheter placement, cholangioplasty, and long-term outcomes were analyzed. Of the 396 consecutive pediatric LT recipients during our study period, 50 (12.6%) were diagnosed with biliary strictures on PTC. LT biliary reconstructions were Roux-en-Y hepaticojejunostomy in 28 patients (56%), choledochojejunostomy in 11 patients (22%), and choledochocholedochostomy in 11 patients (22%). Median age at LT was 23.2 months (interquartile range [IQR], 10.9-90.6), and 14 patients (28%) developed hepatic artery thrombosis. A total of 44 patients (88%) were treated with internal/external biliary catheters, of whom 38 (76%) underwent balloon cholangioplasty. By 12 months, 84% of patients had complete stricture resolution and catheter removal. Median total duration of catheter drainage was 152 days (IQR, 76-308). A total of 8 patients required additional surgery (biliary reconstruction or repeat LT [re-LT]) or died with a drainage catheter in place from complications unrelated to PTC intervention. Among the 6 patients (12%) treated with unilateral external biliary drainage catheters, 2 had catheters removed for inadequate drainage but then had spontaneous biliary obstruction resolution, 1 underwent duct reconstruction, and 3 required long-term catheterization. Biliary strictures following pediatric LT can be successfully treated with internal/external biliary drainage catheters and cholangioplasty if the stricture can be crossed. However, patients with isolated strictured ducts may require long-term external catheter drainage until re-LT or percutaneous obliteration of isolated ducts.

Maternal and Fetal Outcomes in Women with Brain Arteriovenous Malformation Rupture during Pregnancy.

BACKGROUND: Sporadic brain arteriovenous malformations (BAVM) are a major cause of hemorrhagic stroke in younger persons. Prior studies have reported contradictory results regarding the risk of hemorrhage during pregnancy, and there are no standard guidelines for the management of pregnant women who present with BAVM rupture. The purpose of this study is to describe maternal and fetal outcomes and treatment strategies in patients with BAVM hemorrhage during pregnancy. METHODS: We performed a retrospective review of the University of California, San Francisco Brain AVM Project database for female patients who were pregnant at the time of BAVM hemorrhage between 2000 and 2017. Clinical and angiographic characteristics at presentation, BAVM treatment, and maternal outcomes using modified Rankin scale (mRS) score at presentation and 2-year follow-up were recorded. Fetal outcomes were abstracted from medical records and maternal reports. RESULTS: Sixteen patients presented with BAVM hemorrhage during pregnancy, 81% (n = 13) of whom were in their second or third trimester. Three patients (19%) who were in their first trimester terminated or miscarried pregnancy prior to BAVM intervention. Of the remaining 13 patients, 77% (n = 10) received emergent BAVM treatment at time of hemorrhage prior to delivery, and 85% of patients achieved BAVM obliteration and good maternal outcomes (mRS 0-2) at 2-year follow-up. All patients had uncomplicated deliveries (69% cesarean and 23% vaginal) with no reports of postnatal cognitive or developmental delays in infants at 2-year follow-up. CONCLUSIONS: Our study shows good long-term maternal and fetal outcomes in ruptured BAVM patients presenting during pregnancy, the majority who received BAVM interventional treatment prior to delivery.

Normocalcaemic primary hyperparathyroidism: An update on diagnostic and management challenges.

Normocalcaemic primary hyperparathyroidism is a condition that can present with intermittent hypercalcemia or may evolve into hypercalcemic primary hyperparathyroidism. This milder biochemical entity remains incompletely understood because of a lack of long-term health outcomes regarding both medical and surgical approaches to its management. Medical therapies have shown some efficacy. A limited number of studies have found that bisphosphonates increase bone mineral density, and calcimimetics may decrease the risk of nephrolithiasis in patients with normocalcaemic primary hyperparathyroidism. Studies have also described patient outcomes after applying the same surgical criteria used for patients with hypercalcaemic primary hyperparathyroidism to those with the normocalcaemic form of the disease. These studies suggest that parathyroid surgery appears to be effective in normalizing elevated serum parathyroid hormone concentrations and decreasing adverse renal and skeletal outcomes in patients with normocalcaemic hyperparathyroidism. Given the available data and overall lack of consensus regarding the optimal management of these patients, a reasonable approach is to tailor treatment to the individual patient by considering their risk factors for new or accelerated bone loss, kidney stones, diminished quality of life, and cardiovascular disease.

Permissive microbiome characterizes human subjects with a neurovascular disease cavernous angioma.

Cavernous angiomas (CA) are common vascular anomalies causing brain hemorrhage. Based on mouse studies, roles of gram-negative bacteria and altered intestinal homeostasis have been implicated in CA pathogenesis, and pilot study had suggested potential microbiome differences between non-CA and CA individuals based on 16S rRNA gene sequencing. We here assess microbiome differences in a larger cohort of human subjects with and without CA, and among subjects with different clinical features, and conduct more definitive microbial analyses using metagenomic shotgun sequencing. Relative abundance of distinct bacterial species in CA patients is shown, consistent with postulated permissive microbiome driving CA lesion genesis via lipopolysaccharide signaling, in humans as in mice. Other microbiome differences are related to CA clinical behavior. Weighted combinations of microbiome signatures and plasma inflammatory biomarkers enhance associations with disease severity and hemorrhage. This is the first demonstration of a sensitive and specific diagnostic microbiome in a human neurovascular disease.

Rising Incidence and Incidence-Based Mortality of Thyroid Cancer in California, 2000-2017.

CONTEXT: The increased incidence of thyroid cancer globally over the past several decades is principally attributed to small, indolent papillary thyroid cancers. A possible concomitant increase in thyroid cancer-specific mortality remains debated. OBJECTIVE: The changes in thyroid cancer incidence and incidence-based mortality were assessed using a large population-based cohort over an 18-year period. DESIGN & PATIENTS: A retrospective analysis of all thyroid cancers reported in the California Cancer Registry was performed (2000-2017). Age-adjusted incidence and incidence-based mortality rates were analyzed using a log-linear model to estimate annual percent change. RESULTS: We identified 69 684 individuals (76% female, median age 50 years) diagnosed with thyroid cancer. The incidence of thyroid cancer increased across all histological subtypes (papillary, follicular, medullary, and anaplastic) and all tumor sizes. The incidence increased from 6.43 to 11.13 per 100 000 person-years (average increase 4% per year; P < 0.001) over the study period. Thyroid cancer-specific mortality rates increased on average by 1.7% per year (P < 0.001). The increased mortality rates were greater in men (2.7% per year, P < 0.001) and patients with larger tumors (2-4 cm) (3.4% per year, P < 0.05). CONCLUSIONS: Data from this statewide registry demonstrate that the incidence of thyroid cancer is increasing, and that this phenomenon is not restricted to small papillary thyroid cancers. Rising incidence in thyroid cancers of all sizes with concurrent increase of incidence-based mortality in men and those with larger tumors suggest a true increase in clinically significant disease.

The C-terminal fibrinogen-like domain of angiopoietin-like 4 stimulates adipose tissue lipolysis and promotes energy expenditure.

Angptl4 (Angiopoietin-like 4) is a circulating protein secreted by white and brown adipose tissues and the liver. Structurally, Angptl4 contains an N-terminal coiled-coil domain (CCD) connected to a C-terminal fibrinogen-like domain (FLD) via a cleavable linker, and both full-length Angptl4 and its individual domains circulate in the bloodstream. Angptl4 inhibits extracellular lipoprotein lipase (LPL) activity and stimulates the lipolysis of triacylglycerol stored by adipocytes in the white adipose tissue (WAT). The former activity is furnished by the CCD, but the Angptl4 domain responsible for stimulating adipocyte lipolysis is unknown. We show here that the purified FLD of Angptl4 is sufficient to stimulate lipolysis in mouse primary adipocytes and that increasing circulating FLD levels in mice through adenovirus-mediated overexpression (Ad-FLD) not only induces WAT lipolysis in vivo but also reduces diet-induced obesity without affecting LPL activity. Intriguingly, reduced adiposity in Ad-FLD mice was associated with increased oxygen consumption, fat utilization, and the expression of thermogenic genes (Ucp1 and Ppargc1a) in subcutaneous WAT. Moreover, Ad-FLD mice exhibited increased glucose tolerance. Chronically enhancing WAT lipolysis could produce ectopic steatosis because of an overflow of lipids from the WAT to peripheral tissues; however, this did not occur when Ad-FLD mice were fed a high-fat diet. Rather, these mice had reductions in both circulating triacylglycerol levels and the mRNA levels of lipogenic genes in the liver and skeletal muscle. We conclude that separating the FLD from the CCD-mediated LPL-inhibitory activity of full-length Angptl4 reveals lipolytic and thermogenic properties with therapeutic relevance to obesity and diabetes.

Emergency room resource utilization by patients with low-back pain.

OBJECTIVE The objective of this study was to determine factors associated with admission to the hospital through the emergency room (ER) for patients with a primary diagnosis of low-back pain (LBP). The authors further evaluated the impact of ER admission and patient characteristics on mortality, discharge disposition, and hospital length of stay. METHODS The authors conducted a retrospective analysis of patients with LBP discharged from hospitals according to the Nationwide Inpatient Sample (NIS) between 1998 and 2007. Univariate comparisons of patient characteristics according to the type of admission (ER versus non-ER) were conducted. Multivariate analysis evaluated factors associated with an ER admission, risk of mortality, and nonroutine discharge. RESULTS According to the NIS, approximately 183,151 patients with a primary diagnosis of LBP were discharged from US hospitals between 1998 and 2007. During this period, an average of 65% of these patients were admitted through the ER, with a significant increase from 1998 (54%) to 2005 (71%). Multivariate analysis revealed that uninsured patients (OR 2.1, 95% CI 1.7-2.6, p < 0.0001) and African American patients (OR 1.5, 95% CI 1.2-1.7, p < 0.0001) were significantly more likely to be admitted through the ER than private insurance patients or Caucasian patients, respectively. Additionally, a moderate but statistically significant increase in the likelihood of ER admission was noted for patients with more preexisting comorbidities (OR 1.1, 95% CI 1.0-1.2, p < 0.001). An 11% incremental increase in the odds of admission through the ER was observed with each year increment (OR 1.1, 95% CI 1.0-1.2, p < 0.001). Highest income patients ($45,000+) were more likely to be admitted through the ER (OR 1.3, 95% CI 1.1-1.6, p = 0.007) than the lowest income cohort. While ER admission did not impact the risk of mortality (OR 0.95, 95% CI 0.60-1.51, p = 0.84), it increased the odds of a nonroutine discharge (OR 1.39, 95% CI 1.26-1.53, p < 0.0001). CONCLUSIONS A significant majority of patients discharged from hospitals in the US from 1998 to 2007 with a primary diagnosis of LBP were admitted through the ER, with more patients being admitted via this route each year. These patients were less likely to be discharged directly home compared with patients with LBP who were not admitted through the ER. Uninsured and African American patients with LBP were more likely to be admitted through the ER than their counterparts, as were patients with more preexisting health problems. Interestingly, patients with LBP at the highest income levels were more likely to be admitted through hospital ERs. The findings suggest that socioeconomic factors may play a role in the utilization of ER resources by patients with LBP, which in turn appears to impact at least the short-term outcome of these patients.

A crossmodal role for audition in taste perception.

Our sense of taste can be influenced by our other senses, with several groups having explored the effects of olfactory, visual, or tactile stimulation on what we perceive as taste. Research into multisensory, or crossmodal perception has rarely linked our sense of taste with that of audition. In our study, 48 participants in a crossover experiment sampled multiple concentrations of solutions of 5 prototypic tastants, during conditions with or without broad spectrum auditory stimulation, simulating that of airline cabin noise. Airline cabins are an unusual environment, in which food is consumed routinely under extreme noise conditions, often over 85 dB, and in which the perceived quality of food is often criticized. Participants rated the intensity of solutions representing varying concentrations of the 5 basic tastes on the general Labeled Magnitude Scale. No difference in intensity ratings was evident between the control and sound condition for salty, sour, or bitter tastes. Likewise, panelists did not perform differently during sound conditions when rating tactile, visual, or auditory stimulation, or in reaction time tests. Interestingly, sweet taste intensity was rated progressively lower, whereas the perception of umami taste was augmented during the experimental sound condition, to a progressively greater degree with increasing concentration. We postulate that this effect arises from mechanostimulation of the chorda tympani nerve, which transits directly across the tympanic membrane of the middle ear.

Correlation of calcification on excised aortic valves by micro-computed tomography with severity of aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: The quantification of incidentally found aortic valve calcification on computed tomography (CT) is not performed routinely, as data relating to the accuracy of aortic valve calcium for estimating the severity of aortic stenosis (AS) is neither consistent nor validated. As aortic valve calcium quantification by CT is confounded by wall and coronary ostial calcification, as well as motion artifact, the ex-vivo micro-computed tomography (micro-CT) of stenotic aortic valves allows a precise measurement of the amounts of calcium present. The study aim, using excised aortic valves from patients with confirmed AS, was to determine if the amount of calcium on micro-CT correlated with the severity of AS. METHODS: Each of 35 aortic valves that had been excised from patients during surgical valve replacement were examined using micro-CT imaging. The amount of calcium present was determined by absolute and proportional values of calcium volume in the specimen. Subsequently, the correlation between calcium volume and preoperative mean aortic valve gradient (MAVG), peak transaortic velocity (V(max)), and aortic valve area (AVA) on echocardiography, was evaluated. RESULTS: The mean calcium volume across all valves was 603.2 +/- 398.5 mm3, and the mean ratio of calcium volume to total valve volume was 0.36 +/- 0.16. The mean aortic valve gradient correlated positively with both calcium volume and ratio (r = 0.72, p < 0.001). V(max) also correlated positively with the calcium volume and ratio (r = 0.69 and 0.76 respectively; p < 0.001). A logarithmic curvilinear model proved to be the best fit to the correlation. A calcium volume of 480 mm3 showed sensitivity and specificity of 0.76 and 0.83, respectively, for a diagnosis of severe AS, while a calcium ratio of 0.37 yielded sensitivity and specificity of 0.82 and 0.94, respectively. CONCLUSION: A radiological estimation of calcium amount by volume, and its proportion to the total valve volume, were shown to serve as good predictive parameters for severe AS. An estimation of the calcium volume may serve as a complementary measure for determining the severity of AS when aortic valve calcification is identified on CT imaging.

Operative risks and survival in veterans with severe aortic stenosis: surgery versus medical therapy.

BACKGROUND: Transcatheter aortic valves were developed as an alternative to surgery for the one third to two thirds of patients with severe aortic stenosis who do not undergo aortic valve replacement. In this study, we examined reasons for medical management of aortic stenosis in relation to operative risks and outcomes for veterans with and without valve replacement. METHODS: The echocardiography database was screened from 2000 to 2007 for severe aortic stenosis. The Society of Thoracic Surgeons risk scores and survival were determined for patients with and without aortic valve replacement. RESULTS: Of 132 severe aortic stenosis patients included, 42% were medically managed. Predicted operative mortality risk was lower for surgical patients than for medical patients (4.5%±4.2% versus 6.8%±5.1%, p=0.002). Overall, the most common reason for medical management of aortic stenosis was assumption that the patient was high risk for surgery (30.4%). The surgery group had significantly higher median survival (92.2 versus 32.4 months) and 5-year survival (71% versus 37%, p<0.001) than the medical group. Cardiac surgery was not consulted in 61% of medically managed patients, of whom only 18% had Society of Thoracic Surgeons risk score of 10 or greater. Aortic valve replacement was an independent predictor of lower mortality (hazard ratio 0.43, p=0.008). CONCLUSIONS: Although operative risk was higher among patients who did not undergo surgery, most were not the 10% or greater required for transcatheter valves. Given the significantly lower survival with medical therapy, aortic valve replacement should be carefully considered for most severe aortic stenosis patients whereas transcatheter aortic valves should be reserved for patients with high operative risks.