Asymptomatic Abnormalities Research Articles

Abstract 11157: A Rare Case of Concomitant Dual Genetic Cardiomyopathies in a Patient Complicated by Stroke

Background: Very little evidence exists on the prevalence of co-existing cardiomyopathies. We report in this case a highly atypical presentation of concurrent arrhythmogenic right ventricular cardiomyopathy (ARVC) and hypertrophic cardiomyopathy (HCM) likely attributable to simultaneous separate somatic mutations, complicated by stroke. Case: A 60-year-old male with a history of rheumatoid arthritis, sleep apnoea and obesity with no significant coronary disease referred for review of asymptomatic ECG abnormalities was found to have severe asymmetrical left ventricular (LV) wall thickening with apical segment akinesis and an LV apex mass on echocardiogram. She had a family history of early sudden cardiac death, with an otherwise unremarkable history and physical examination. Clinical Course: Cardiac MRI (CMR) subsequently demonstrated aneurysmal dilatation of LV apical segments with a 17x13mm thrombus present. Systolic anterior mitral leaflet motion was seen, and a dilated right ventricle (RV) with 240ml end-diastolic volume and 27% ejection fraction. "Accordion" sign was present in the sub-tricuspid RV free wall with dyskinesia, and ECGs confirmed presence of epsilon waves. One week after CMR, she suffered a large left middle cerebral artery (MCA) stroke in the setting of warfarin cessation due to echocardiography-suggestive absence of thrombus. Discussion: Genetic analysis revealed a mutated Plakophillin 2 (PKP2) gene, and FHOD3 gene associated with HCM of uncertain significance. The diagnosis was concomitant genetic cardiomyopathies of ARVC and HCM complicated by large LV apical aneurysm and thrombus culminating in left MCA stroke. PKP2 mutations to date have not been associated with hypertrophic phenotypes. This case therefore demonstrates the unlikely 1 in 2,500 incidence of coexistence of two separate cardiomyopathies likely attributable to simultaneous separate somatic mutations, while also highlighting the central role of CMR in investigation and diagnosis of RV pathology. In addition to this case, prior studies have also shown echocardiography can only identify 50% of ARVC cases identified by CMR, suggesting that selective use of CMR may double the number of identified cases of this life-threatening disease.

Asymptomatic Renal Function Abnormalities in Patients having Silicosis.

A number of occupational exposures are associated with various types of renal dysfunction. Several studies for many years have drawn attention to renal dysfunction and nephrotoxicity among workers exposed to silica. This study was conducted to evaluate renal dysfunction, if any, among Indian patients having silicosis and its correlation with the duration of exposure to silica dust. This study includes 52 eligible patients with a history of silica dust exposure and silicosis confirm on radiological examination by the pneumoconiosis board. Investigations like serum creatinine, urinary albumin creatinine ratio, etc. were done. The "modification of diet in renal disease" (MDRD) formula was used to calculate the glomerular filtration rate (GFR). This study showed 53.84% of patients (n = 28) having albuminuria and a mean "urinary albumin to creatinine ratio" (UACR) of 101.88 ± 128.99 mg/gm. Isolated macroalbuminuria was detected in 11.5% of patients (n = 6) while 42.3% of patients (n = 22) presented with microalbuminuria. The mean GFR was 81.94 ± 22.09 mL/min/1.73 m2 among study patients of which four (7.7%) patients had GFR value <60 mL/min/1.73 m2 . We could also identify a significant association between the duration of exposure to silica dust and UACR and GFR (p < 0.01). Albuminuria and reduced estimated GFR in patients with silica dust exposure is not uncommon and reflect early underlying renal dysfunctions. Our study suggests a simple and cost-effective screening strategy for early detection of renal dysfunction among silicosis patients that may be considered as a tool to prevent further renal damage in such patients.

Short-term outcome and complications of therapeutic hypothermia in neonates with moderate-to-severe hypoxic ischaemic encephalopathy: a single-centre retrospective observational study in a hospital in Mumbai, India

ABSTRACT Background Although shown to reduce death or disability in moderate-to-severe hypoxic ischaemic encephalopathy (HIE), therapeutic hypothermia (TH) has recently been associated with an increase in adverse events in low- and middle-income countries (LMIC). Aim To determine the clinical characteristics, complications and short-term outcome in neonates receiving TH in King Edward Memorial Hospital, Mumbai, India. Methods A retrospective single-centre study of neonates with moderate-to-severe HIE who received TH from 1 January 2018 to 31 December 2021 was undertaken. TH was provided as per the unit’s protocol using either a servo-controlled device or a phase-changing material (PCM). Results One hundred and fifty-five neonates were included with 94.2% intramural births. Mean gestation and birthweight were 38.6 (1.5) weeks and 2776.7 (431) g, respectively. HIE staging was moderate in 87.1% and severe in 12.9%, with a mean cord pH of 6.93 (0.14) and seizures in 38.7%. Adverse events included shock (50.3%), clinically significant bleeding (16%), acute kidney injury (6.7%), culture-positive sepsis (11.6%), persistent pulmonary hypertension (9%), bradycardia (9%), food intolerance (14.9%) and premature termination (7.1%). A servo-controlled device (15.5%) or PCM (84.5%) was used, with comparable adverse events. 84.5% of the neonates were discharged, 7.1% discharged against medical advice and 8.4% died. Detailed neurological assessment at discharge/discharge against medical advice suggested neurological impairment in 128 (87.1%) neonates. Conclusion Adverse events during TH range from asymptomatic laboratory abnormalities to life-threatening complications, which are manageable in well equipped units. Neurological impairment at discharge in neonates who received cooling mandates strict neurological follow-up. Abbreviations: aEEG: amplitude-integrated EEG; AKI: acute kidney injury; BW: birthweight; EEG: electro-encephalogram; GA: gestational age; HELIX: hypothermia for encephalopathy in low- and middle-income countries; HIE: hypoxic ischaemic encephalopathy; IVH: intraventricular haemorrhage; LMIC: low- and middle-income countries; NICHD: National Institute of Child Health and Human Development; NICU: neonatal intensive care unit; PPHN: persistent pulmonary hypertension of newborn; PCM: phase-changing material; SGA: small-for-gestational age; TH: therapeutic hypothermia.

S2182 A Case of Colonic Malakoplakia

Introduction: Malakoplakia is a rare histiocytic inflammatory response that is usually found in the urinary tract. Gastrointestinal involvement is considered the second most common location affected and is a result of dysfunctional macrophages. Histopathology is characterized by granular histiocytes with Micahelis-Gutmann bodies. Although usually an incidental finding, Malakoplakia is associated with immunosuppressive therapy, colorectal carcinoma and infectious diseases. Case Description/Methods: A 54-year-old man with a pmhx of alcohol use disorder was referred to clinic for acute, asymptomatic liver enzyme abnormalities. Laboratory findings were significant for AST of 270 U/L, ALT of 63 U/L, ALP of 65 U/L, and total bilirubin of 0.3 mg/dL. Further workup showed positive hepatitis B surface antigen, reactive hepatitis B core antibody and hepatitis B DNA by PCR was 172K IU/mL. Patient underwent screening colonoscopy which revealed a 2 mm sessile polyp in the cecum (Figure A). Histological examination of the polyp showed von-Hansemann cells containing Michaelis-Gutmann bodies, which is diagnostic for malakoplakia (Figure B). Discussion: The first report of colonic malakoplakia was described by Terner and Lattes in 1965 and usually involves the ascending colon, sigmoid colon and rectum. Clinical manifestations of colonic involvement range from asymptomatic to abdominal pain, fever, diarrhea and rectal bleeding. The lesion is characterized by von-Hansemann cells which are aggregates of histiocytes with eosinophilic cytoplasm and intracytoplasmic Michaelis-Gutmann bodies. Pathogenic mechanisms include a causative organism, altered immune response and phagocyte disfunction. Escherichia coli is the most common isolated pathogen found in 90% of patients with malakoplakia. These chronic bacterial infections are due to suspected abnormal macrophage function resulting in the inability to break down bacteria. The most susceptible include immunosuppressed patients who are post-transplant or have an untreated systemic disease such as chronic hepatitis. Antibiotic therapy, immunotherapy modification and surgical resection are the mainstay of management. While most cases of malakoplakia are diagnosed as incidental findings on screening colonoscopy, there does exist an associate with colorectal adenocarcinoma. Given the potential for significant morbidity if left untreated, malakoplakia diagnosed on incidental screening should prompt a work up for systemic infections, immune compromising diseases and malignancy.Figure 1.: A: Two mm cecum polyp denoted by yellow arrows. Figure B: High-power view of Malakoplakia (60x). Macrophages containing basophilic targetoid structures, known as Michaelis-Gutmann bodies.

S812 Hepatic Safety of Ozanimod in Ulcerative Colitis and Relapsing Multiple Sclerosis Phase 3 Trials

Introduction: Ozanimod (OZA) is a sphingosine 1-phosphate (S1P) receptor modulator approved for the treatment of moderately to severely active ulcerative colitis (UC) and relapsing forms of multiple sclerosis (MS) in the United States and European Union. Other S1P receptor modulators have shown substantial elevations in hepatic enzymes. Methods: The impact of OZA on liver function tests was assessed in this safety analysis from phase 3 UC and MS trials. In the 52-week (10-week induction period and 42-week maintenance period), randomized True North (TN) trial, patients (pts) with moderately to severely active UC were treated with placebo (n=216) or OZA 0.92 mg (equivalent to OZA HCl 1 mg) (n=796). In the randomized MS trials (SUNBEAM and RADIANCE), MS pts were treated with interferon beta-1a 30 µg (n=885) or OZA (n=882) for 12 and 24 months, respectively. Hepatic enzymes were assessed at baseline and Weeks 5, 10, 18, 28, 40, and 52 in TN, and at baseline and every 3 months for the MS trials. In the UC and MS trials, enzyme elevations were confirmed with a repeated test within 14 days. Results: Percentages of pts on OZA 0.92 mg with elevations in alanine transaminase (ALT), aspartate aminotransferase (AST), and bilirubin are shown in the Table; < 6% and < 2% of pts had ALT and AST elevations ≥3 x upper limit of normal (ULN), respectively, and < 2% had bilirubin elevations >2 x ULN. Of those with ALT ≥3 x ULN, 86.4% (19/22) of UC pts and 85.4% (41/48) of MS pts recovered to ALT < 3 x ULN within 3 months. Most hepatic treatment-emergent adverse events (TEAEs) were mild to moderate in UC and MS pts. In TN, 3 (0.4%) pts on OZA reported a hepatobiliary disorder TEAE, 1 (0.1%) of whom had hyperbilirubinemia. In the MS trials, 15 (1.7%) pts on OZA 0.92 mg reported a hepatobiliary disorder TEAE, 3 (0.3%) of whom had hyperbilirubinemia. Hepatic-related events leading to discontinuation, which were generally asymptomatic laboratory abnormalities, were reported in 4 (0.5%) UC pts and in 11 (1.2%) MS pts on OZA 0.92 mg. No serious hepatic TEAEs, Hy’s law cases, or severe drug-induced hepatocellular injuries occurred with OZA 0.92 mg in any of the trials. Conclusion: In this analysis of phase 3 UC and MS trials with OZA, elevations of aminotransferases and bilirubin occurring with OZA were infrequent, generally asymptomatic, and transient. These elevations, which generally resolved without study drug discontinuation, did not meet the criteria for Hy’s law or protocol-defined serious AEs. Table 1. - Maximum postbaseline ALT, AST, and bilirubin levels with OZA 0.92 mg Parameter TN (UC)(n=783) Sunbeam/Radiance (MS) (n=878) ALT >1 × ULN 215 (27.5) 373 (42.5) ≥3 × ULN 22 (2.8) 48 (5.5) ≥5 × ULN 8 (1.0) 14 (1.6) AST >1 × ULN 136 (17.4) 185 (21.1) ≥3 × ULN 14 (1.8) 9 (1.0) ≥5 × ULN 5 (0.6) 5 (0.6) Bilirubin >1 × ULN 32 (4.1) 122 (13.9) >2 × ULN 3 (0.4) 14 (1.6) >3 × ULN 1 (0.1) 3 (0.3)

S3373 Atypical GBS as the Presenting Symptom of Celiac Disease: Recognizing Extra-intestinal Presentations of Celiac Disease

Introduction: Celiac disease (CD) is an immune-mediated enteropathy in response to gluten that occurs in 1% of the population. Classic presenting symptoms include bloating, weight loss, and diarrhea. But, extraintestinal symptoms such as dermatitis herpetiformis, iron deficiency anemia, asymptomatic liver abnormalities, and more rarely, neurologic symptoms can be seen. We present a case of a patient who presented with worsening polyneuropathy and hepatitis leading to a final diagnosis of CD. Case Description/Methods: A 44-year-old male with history of recent left-chest shingles complicated by paralysis of right face and left leg weakness was initially admitted for suspected atypical Guillain Barre Syndrome (GBS) and treated with prednisone and a 5-day course of intravenous immunoglobulin (IVIG). The patient was readmitted a few weeks later with worsening neurologic status. A thorough infectious workup was unremarkable. The patient was also noted to have abnormal liver enzymes on prior admission that initially improved, but were noted to be worse on readmission up to ALP 1103, AST 634 and ALT 689. Given no prior history of liver disease, patient underwent a thorough workup including negative viral hepatitis, normal liver US, abdominopelvic CT showed scattered hypoattenuating lesions in the liver, one measuring up to 2.2 cm. He underwent a liver biopsy which demonstrated acute hepatitis with findings concerning for autoimmune versus drug-induced hepatitis. Autoimmune hepatitis panel was negative, however, he was found to have a tissue transglutaminase IgA >250 U/mL. Finally, he underwent upper endoscopy with biopsies that demonstrated findings consistent with celiac disease. Liver enzymes improved with gluten avoidance, but neurologic impairments persisted. Discussion: Atypical extra-intestinal symptoms at presentation of CD can result in diagnostic delay and permanent neurological disability if not treated. CD has been found in as many as 9% of patients with elevated liver enzymes. It is imperative not only to recognize neurologic presentations of CD but also the spectrum of possible liver impairments. Adherence to a strict gluten-free diet has been shown to improve symptoms of both neuropathy and liver enzyme abnormalities, but must be instituted quickly.

Porto-sinusoidal vascular disorder.

It is well established that portal hypertension can occur in the absence of cirrhosis, as reported in patients with immune disorders, infections and thrombophilia. However, similar histological abnormalities primarily affecting the hepatic sinusoidal and (peri)portal vasculature have also been observed in patients without portal hypertension. Thus, the term porto-sinusoidal vascular disorder (PSVD) has recently been introduced to describe a group of vascular diseases of the liver featuring lesions encompassing the portal venules and sinusoids, irrespective of the presence/absence of portal hypertension. Liver biopsy is fundamental for PSVD diagnosis. Specific histology findings include nodular regenerative hyperplasia, obliterative portal venopathy/portal vein stenosis and incomplete septal fibrosis/cirrhosis. Since other conditions including alcohol-related and non-alcoholic fatty liver disease, or viral hepatitis, or the presence of portal vein thrombosis may occur in patients with PSVD, their relative contribution to liver damage should be carefully assessed. In addition to histology and clinical diagnostic criteria, imaging and non-invasive tests such as liver and spleen stiffness measurements could aid in the diagnostic workup. The introduction of PSVD as a novel clinical entity will facilitate collaborative studies and investigations into the underlying molecular pathomechanisms encompassed by this term.

Linac-based stereotactic radiosurgery for brain arteriovenous malformations

PurposeLinac stereotactic radiosurgery (SRS) is gaining popularity as a form of radiation treatment for cerebral arteriovenous malformations (AVMs) since the theory of combined radiosurgical and endovascular treatment poses much uncertainty and due to significant technical progress for SRS. This study focuses on how to evaluate obliteration and re-bleeding rates, and to determine factors and adverse effects influencing obliteration after linac-based SRS for cerebral AVMs.Material and methodsFrom a statistical record of 71 patients, 31 had partial embolisation, five surgery and 29 had no prior treatment. Using Kaplan–Meier survival and life table analyses, actuarial obliteration and annual bleeding hazard rates were calculated after SRS.ResultsAfter a follow up of 1, 2 and 3 years the actual obliteration rates were 22, 59 and 66%, respectively whereby it was noted that prior embolization had no effect on the obliteration rate. Annual bleeding hazard rates were further analyzed after stereotactic radiosurgery to be 2.1% and 1.4% for the first and second year respectively. Asymptomatic abnormalities were detected after imaging in 33.9% of patients. A dose of less than 18 Gy significantly reduced the obliteration probability.ConclusionSRS is a therapeutic option for intracerebral AVM. In general, there is a low rate of morbidity and a high probability of nidus obliteration.

Randomized, placebo-controlled, single-blind phase 1 studies of the safety, tolerability, and pharmacokinetics of BRII-196 and BRII-198, SARS-CoV-2 spike-targeting monoclonal antibodies with an extended half-life in healthy adults.

Background: BRII-196 and BRII-198 are two anti-SARS-CoV-2 monoclonal neutralizing antibodies as a cocktail therapy for treating COVID-19 with a modified Fc region that extends half-life. Methods: Safety, tolerability, pharmacokinetics, and immunogenicity of BRII-196 and BRII-198 were investigated in first-in-human, placebo-controlled, single ascending dose phase 1 studies in healthy adults. 44 participants received a single intravenous infusion of single BRII-196 or BRII-198 up to 3,000 mg, or BRII-196 and BRII-198 combination up to 1500/1500 mg, or placebo and were followed up for 180 days. Primary endpoints were incidence of adverse events (AEs) and changes from pre-dose baseline in clinical assessments. Secondary endpoints included pharmacokinetics profiles of BRII-196/BRII-198 and detection of anti-drug antibodies (ADAs). Plasma neutralization activities against SARS-CoV-2 Delta live virus in comparison to post-vaccination plasma were evaluated as exploratory endpoints. Results: All infusions were well-tolerated without systemic or local infusion reactions, dose-limiting AEs, serious AEs, or deaths. Most treatment-emergent AEs were isolated asymptomatic laboratory abnormalities of grade 1-2 in severity. BRII-196 and BRII-198 displayed pharmacokinetics characteristic of Fc-engineered human IgG1 with mean terminal half-lives of 44.6–48.6 days and 72.2–83.0 days, respectively, with no evidence of interaction or significant anti-drug antibody development. Neutralizing activities against the live virus of the SARS-CoV-2 Delta variant were maintained in plasma samples taken on day 180 post-infusion. Conclusion: BRII-196 and BRII-198 are safe, well-tolerated, and suitable therapeutic or prophylactic options for SARS-CoV-2 infection. Clinical Trial Registration: ClinicalTrials.gov under identifiers NCT04479631, NCT04479644, and NCT04691180.

Circulating MicroRNAs as Potential Biomarkers for Ischemic Stroke in Patients with Asymptomatic Intracranial Artery Stenosis.

Circulating microRNAs have been shown to be biomarkers of various diseases. We aimed to investigate whether circulating microRNA can serve as a biomarker to predict ischemic stroke risk in asymptomatic intracranial artery stenosis. A total of 716 participants from the Asymptomatic Polyvascular Abnormalities Community study who had asymptomatic intracranial artery stenosis at baseline were enrolled (2010-11). Patients who suffered incident ischemic stroke were classified into the case group, and age- and sex-matched individuals without stroke were used as controls. MicroRNA microarrays were used to distinguish baseline circulating serum microRNA levels between the case and the control groups (GEO accession number GSE201860). The differentially expressed microRNAs were validated by real-time PCR. MicroRNA microarrays were performed in baseline serum samples from12 subjects who developed ischemic stroke and 12 age- and sex-matched subjects without stroke during the 2014-15 follow-up period. Twenty microRNAs were differentially expressed between the two groups (fold change > 1.3 and p < 0.05 for all). Hsa-miR-486-5p, hsa-miR-92a-3p, hsa-miR-6089 from them were selected and validated in the baseline serum samples of ten subjects with incident ischemic stroke and another ten age- and sex-matched subjects without stroke during the 2016-17 follow-up period. Hsa-miR-1225-5p, with a large fold change value and a reported relationship with cardiovascular or cerebrovascular diseases, was also validated. Ultimately, only hsa-miR-6089 was differentially downregulated among patients with intracranial artery stenosis who developed ischemic stroke (p < 0.05). In patients with asymptomatic intracranial artery stenosis, downregulated serum hsa-miR-6089 may be associated with the risk of ischemic stroke.

Real-World Efficacy and Tolerability of Brigatinib in Patients with Non-Small Cell Lung Cancer with Prior ALK-TKIs in the United States.

BackgroundReal-world evidence for brigatinib, a next-generation anaplastic lymphoma kinase-tyrosine kinase inhibitor (ALK-TKI) used in ALK-rearranged non-small cell lung cancer, is scarce. This retrospective study evaluated real-world brigatinib utilization in the US post other ALK-TKIs.Materials and MethodsAdults with ≥1 brigatinib claim (index date) between 1 April 2017 and 30 September 2020 in the IQVIA longitudinal pharmacy claims database were followed until dose reduction, discontinuation, or end of follow-up. Patients had ≥12 months pre– and ≥1-month post–index observations.ResultsA total of 413 patients treated with brigatinib were analyzed. Over 80% received ≥1 prior ALK-TKI; alectinib and crizotinib were the most common (58.8% and 51.3% patients, respectively). The median follow-up was 8.4 months. The median time to treatment discontinuation (TTD) for brigatinib was 10.3 months (95% CI, 8.2-15.0), with 45% remaining on therapy at 12 months. The TTD was shortest (~8 months) in patients receiving both crizotinib and alectinib and longest in patients who received alectinib only prior to brigatinib (11.8 months). Adherence was high, with 92.7% of patients having a medication possession ratio of >80%. The mean dose compliance score was 1.0. Most patients reached the brigatinib dose of 180 mg/day (77%); 13.2% of patients had a dose reduction, with 89.3% and 84.6% continuing 180 mg/day therapy at 3 and 6 months, respectively.ConclusionsBrigatinib appears to be effective and well-tolerated in the real-world ALK+ NSCLC population in the US, showing benefit in patients after a next-generation ALK-TKI. Notably, dose reduction rates appeared markedly less than those seen in trials when most trial-related dose reductions were for asymptomatic laboratory abnormalities.

Coronary Artery Connection Abnormalities: About Four Cases

Coronary artery connection abnormalities are a diverse group of congenital disorders whose manifestations and pathological mechanisms are highly variable. This abnormalities are undergoing significant changes in terms of description, morphogenesis, clinical presentation, diagnostic assessment, prognosis and treatment. It is an important entity because of its clinical impact, the risk of sudden death, its prevalence and its practical management. The rapid development of imaging techniques such as computed tomography, magnetic resonance imaging, intravascular ultrasound and optical coherence tomography has brought a lot of new information on the issue. It is most often associated with sudden cardiac mortality if the abnormal connection of a coronary artery from the controlateral sinus, especially if it passes between the aorta and the pulmonary artery. Patients are often asymptomatic and coronary abnormalities are incidentally identified during coronary angiography or autopsy after sudden cardiac death in the majority of cases. Symptoms such as angina pectoris, syncope, heart failure and myocardial infarction can occur under certain circumstances. The purpose of this article is to provide a brief overview of the various variants of this disease, focusing on some clinical manifestations, the risk of sudden cardiac death and the physiopathological mechanism of symptoms, as well as valuable information on diagnostic assessment and treatment options.

Musculoskeletal ultrasound of the shoulder in systemic sclerosis.

To explore shoulder findings by ultrasonography and to find factors associated with shoulder ultrasonographic abnormalities in systemic sclerosis patients. A series of systemic sclerosis patients who attended the scleroderma clinic, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand, were prospectively evaluated for baseline characteristics, physical examination, and ultrasonography of both shoulders. Seventy-four systemic sclerosis patients were enrolled in this study. Diffuse cutaneous type of systemic sclerosis was the most common type (62.2%). The three common systemic sclerosis-associated symptoms were skin tightness (28.5%), salt-pepper appearance (20.9%), and telangiectasia (11.6%). The prevalence of shoulder pain in systemic sclerosis patients was 43.2% (32/74). Sixty-eight patients (92%) had abnormal ultrasonographic findings. The most common ultrasonographic abnormalities were unilateral calcification inside the glenohumeral joint (45.9%), bilateral calcification inside the glenohumeral joint (36.5%), and bilateral supraspinatus tendinosis (28.9%). Skin edematous was the only factor associated with abnormal shoulder ultrasonographic findings. No association between shoulder pain and abnormal shoulder ultrasonographic findings was detected. Ultrasonographic abnormalities in the shoulder were common in the systemic sclerosis patients. The most frequent ultrasonographic finding of shoulder joints in systemic sclerosis patients was calcification inside the glenohumeral joint. Moreover, asymptomatic shoulder ultrasonographic abnormalities were prevalent in individuals with systemic sclerosis.

The Use of Lipoprotein-Associated Phospholipase A2 in a Chinese Population to Predict Cardiovascular Events

ObjectiveTo explore associations between lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular events in a Chinese population, with a long-term follow-up. MethodsA random sample of 2,031 participants (73.6% males, mean age = 60.4 years) was derived from the Asymptomatic Polyvascular Abnormalities Community study (APAC) from 2010 to 2011. Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). The composite endpoint was a combination of first-ever stroke, myocardial infarction (MI) or all-cause death. Lp-PLA2 associations with outcomes were assessed using Cox models. ResultsThe median Lp-PLA2 level was 141.0 ng/mL. Over a median follow-up of 9.1 years, we identified 389 events (19.2%), including 137 stroke incidents, 43 MIs, and 244 all-cause deaths. Using multivariate Cox regression, when compared with the lowest Lp-PLA2 quartile, the hazard ratios with 95% confidence intervals for developing composite endpoints, stroke, major adverse cardiovascular events, and all-cause death were 1.77 (1.24–2.54), 1.92 (1.03–3.60), 1.69 (1.003–2.84), and 1.94 (1.18–3.18) in the highest quartile, respectively. Composite endpoints in 145 (28.6%) patients occurred in the highest quartile where Lp-PLA2 (159.0 ng/mL) was much lower than the American Association of Clinical Endocrinologists recommended cut-off point, 200 ng/mL. ConclusionHigher Lp-PLA2 levels were associated with an increased risk of cardiovascular event/death in a middle-aged Chinese population. The Lp-PLA2 cut-off point may be lower in the Chinese population when predicting cardiovascular events.

Why Are Women Predisposed to Intracranial Aneurysm?

Intracranial aneurysm (IA) is a frequent and generally asymptomatic cerebrovascular abnormality characterized as a localized dilation and wall thinning of intracranial arteries that preferentially arises at the arterial bifurcations of the circle of Willis. The devastating complication of IA is its rupture, which results in subarachnoid hemorrhage that can lead to severe disability and death. IA affects about 3% of the general population with an average age for detection of rupture around 50 years. IAs, whether ruptured or unruptured, are more common in women than in men by about 60% overall, and more especially after the menopause where the risk is double-compared to men. Although these data support a protective role of estrogen, differences in the location and number of IAs observed in women and men under the age of 50 suggest that other underlying mechanisms participate to the greater IA prevalence in women. The aim of this review is to provide a comprehensive overview of the current data from both clinical and basic research and a synthesis of the proposed mechanisms that may explain why women are more prone to develop IA.

Electrocardiographic abnormalities in the setting of acute central nervous system pathology

Up to 90% of patients with acute central nervous system lesions, such as stroke, exhibit secondary ECG abnormalities, including ST elevation/depression, T wave inversion, prominent U wave, prolonged QTc interval, sinus bradycardia/pause and atrioventricular block. The pathophysiology involves autonomic nervous system disturbance resulting in altered ventricular repolarization gradients, or even myocardial lesions. Clinical assessment aims at distinguishing asymptomatic neurogenic ECG abnormalities from organic heart conditions such as Takotsubo syndrome, myocardial infarction and chronic coronary syndromes. Serial ECG, cardiac biomarkers and echocardiography should be performed, followed by targeted work-up in selected patients. Prolonged QT, arrhythmias or hemodynamic compromise require continuous monitoring and standard management.

Cholestatic jaundice - an enigmatic form of "hepatic" thyrotoxicosis

Background and Aim: Asymptomatic abnormalities of liver function tests are common in hyperthyroidism. However, severe cholestatic jaundice with markedly elevated transaminases is rarely described in thyrotoxicosis as seen in our case.

Risk factors for asymptomatic echocardiographic abnormalities that predict symptomatic heart failure.

AimsRisk factors for asymptomatic echocardiographic abnormalities that predict symptomatic heart failure (HF) may provide insight into early mechanisms of HF pathogenesis. We examined risk factors associated with asymptomatic echocardiographic structural, systolic, and diastolic abnormalities, separately and in combination, and interactions between risk factors, in the prospective community‐based SCReening Evaluation of the Evolution of New HF (SCREEN‐HF) Study cohort of 3190 participants at increased risk of cardiovascular disease.Methods and resultsInclusion criteria were age ≥ 60 years with one or more of hypertension, diabetes, ischaemic heart disease, valvular heart disease, abnormal heart rhythm, cerebrovascular disease, or renal impairment. Exclusion criteria were known HF, ejection fraction < 50%, or >mild valve abnormality. Structural, systolic, and diastolic echocardiographic abnormalities were defined according to the Atherosclerosis Risk in Communities study criteria, and risk factors for asymptomatic structural, systolic, and diastolic abnormalities were identified using logistic regression analysis. In multivariable analysis, increased body mass index (BMI), non‐steroidal anti‐inflammatory drug therapy, and alcohol intake were risk factors for isolated structural abnormality, whereas male gender, increased heart rate, atrial fibrillation (AF), angiotensin‐converting enzyme inhibitor therapy, and obstructive sleep apnoea were associated with a lower risk. Moreover, male gender, smoking, increased systolic blood pressure, and physical inactivity were risk factors for isolated systolic abnormality, whereas increased pulse pressure and antihypertensive therapy were associated with a lower risk. Furthermore, increased age, blood pressure, amino‐terminal pro‐B‐type natriuretic peptide level, and warfarin therapy (associated with AF) were risk factors for isolated diastolic abnormality, whereas increased heart rate and triglyceride level (associated with BMI) were associated with a lower risk. The association of increased heart rate with lower risk of structural and diastolic abnormalities was independent of β‐blocker therapy. Interactions between risk factors differed for structural, systolic, and diastolic abnormalities.ConclusionsThe different risk factors for asymptomatic structural, systolic, and diastolic abnormalities that predict symptomatic HF, and the interactions between risk factors, illustrate how these structural, systolic, and diastolic abnormalities represent unique trajectories that lead to symptomatic HF. Improved understanding of these trajectories may assist in the design of HF prevention strategies.

Sonographic Screening of Distance Runners for the Development of Future Achilles and Patellar Tendon Pain.

The 2 primary aims of this study were to identify ultrasonographic tendon abnormalities in asymptomatic runners and to examine the likelihood of developing pain in runners with ultrasound abnormalities compared with those without abnormalities. Longitudinal, prospective cohort study. 2019 Salt Lake City Marathon. Recreational half-marathon and full-marathon runners. The Achilles and patellar tendons of asymptomatic runners were examined with ultrasound imaging before a running event. Runners were monitored for self-reported outcomes of pain in the examined tendons at 1, 3, 6, and 12 months after the event. Development of pain based on the presence of asymptomatic tendon abnormalities. One hundred thirty-eight runners (36.2 ± 12.0 years, 49.3% men, and 31.2% full-marathon runners) were included. Ultrasound abnormalities of the Achilles and patellar tendons were identified in 24.6% and 39.1% of the runners before the race, respectively. Ultrasound abnormalities were significantly associated with approximately a 3-fold increase [hazard ratio (HR) = 2.55, P = 0.004] in the hazard of developing pain in the Achilles tendon and patellar tendon (HR = 1.67, P = 0.042) over the year after the race. Positive and negative predictive values of developing pain over the year were 34.1% and 87.2%, respectively, for abnormal findings in the Achilles tendon, and 22.9% and 85.0%, respectively, for the patellar tendon. The presence of ultrasonographic abnormalities is associated with increased development of pain in the Achilles and patellar tendons within 1 year of a marathon or half marathon.

Pulmonary sarcoid-like granulomatosis during etanercept treatment for inflammatory arthritis: A case series and literature review

Rationale: Tumor necrosis factor-alpha (TNF-α) inhibitors have been implicated in the development of sarcoid-like granulomatous inflammation when used for treatment of a variety of immune-related diseases. The mechanisms are not completely understood, and the clinical, radiographic and histologic findings of this condition require further description. The literature surrounding this is largely limited to single case reports. Objectives: The objective of this study was to describe pulmonary sarcoid-like granulomatosis in 5 patients receiving etanercept therapy prescribed for inflammatory arthritis. Methods: We retrospectively reviewed the medical records of 5 patients who developed granulomatous sarcoid-like manifestations while on treatment with etanercept for inflammatory arthritis. Data surrounding clinical features and radiographic and histologic findings, as well as clinical outcomes, were described. Results: Median time from initiation of treatment to development of symptoms was 36 months (range 7-60 months). All patients had radiographic abnormalities on chest imaging, with 4 patients having adenopathy on thoracic imaging, and 2 of the 5 patients having parenchymal involvement. Biopsy evidence of granulomatous inflammation was seen in all patients. Three of 5 patients had discontinuation of etanercept when the diagnosis was made, and all experienced improvement. Of the 2 patients that were continued on etanercept, 1 had spontaneous improvement and the other had stable, asymptomatic radiographic abnormalities. Only 1 patient was treated with corticosteroids. Conclusion: Pulmonary sarcoid-like granulomatosis is incompletely understood and establishing the causal role of these drugs in sarcoid-like lung disease is difficult. We hope that the addition of these 5 cases of etanercept-related pulmonary sarcoid-like granulomatosis will add to our future understanding of this response to etanercept and other anti-TNF-α agents.