Clinical predictors and outcomes of pulmonary infarction in patients with central pulmonary embolism.

BACKGROUND: Given the heterogeneity of predisposing factors associated with pulmonary infarction (PI) and the lack of clinically relevant outcomes among patients with acute pulmonary embolism (PE) complicated by PI, further investigation is required. METHODS: Retrospective study of patients with central PE in an 11-year period. Data were stratified according to the diagnosis of PI. Multivariable logistic regression analysis was used to analyze factors associated with PI development and determine if PI was associated with severe hypoxemic respiratory failure and mechanical ventilation use. RESULTS: Of 645 patients with central PE, 24% (n = 156) had PI. After adjusting for demographics, comorbidities, and clinical features on admission, only age (OR 0.98, CI 0.96-0.99; p = 0.008) was independently associated with PI. Regarding outcomes, 35% (n = 55) had severe hypoxemic respiratory failure, and 19% (n = 29) required mechanical ventilation. After adjusting for demographics, PE severity, and right ventricular dysfunction, PI was independently associated with severe hypoxemic respiratory failure (OR 1.78; CI 1.18-2.69, p = 0.005) and mechanical ventilation (OR 1.92; CI 1.14-3.22, p = 0.013). CONCLUSIONS: Aging is a protective factor against PI. In acute central PE, subjects with PI had higher odds of developing severe hypoxemic respiratory failure and requiring mechanical ventilation.

A study of doubt in obsessive-compulsive disorder.

BACKGROUND AND OBJECTIVES: Obsessive-compulsive disorder (OCD) has been referred to as the "doubting disease," yet there has been little foundational research on its phenomenology and characteristics. Studies of doubt have relied on researchers' idiosyncratic conceptualizations of the construct, resulting in varied assessment methods and different prevalence rates (11-75%). We examined the nature and characteristics of doubt in people with clinical and subclinical OCD so as to identify its nature and characteristics, and factors that may be unique to OCD. METHODS: A semi-structured interview about doubt was administered to people with OCD (N = 44) and with subclinical OCD (N = 21). RESULTS: Doubt was highly prevalent and manifested as a form of obsession, uncertainty about whether a task was done properly, and/or lack of confidence in memory and perceptions. All participants took action to resolve doubt and/or proactively pre-empt or reduce future doubt. Doubt was deeply connected to negative core beliefs about the self. The groups did not differ on their experience of doubt, except that greater symptom severity was associated with greater interference from doubt, less ability to resist it, and less success of proactive, but not reactive, strategies to manage it. LIMITATIONS: We relied on retrospective report, and the subclinical group was relatively small. CONCLUSIONS: In subclinical and clinical OCD, doubt is pervasive, manifests in three domains, is connected to negative core beliefs, and is highly aversive. Continued empirical study of doubt is essential to proper assessment and to development of theories and treatment of OCD.

Clinical features and risk factors of adverse clinical outcomes in central pulmonary embolism using machine learning analysis.

BACKGROUND: In prior studies, central pulmonary embolism (PE) was associated with high clot burden and was considered an independent predictor for thrombolysis. Further information about predictors of adverse outcomes in these patients is needed for better risk stratification. The objective is to describe independent predictors of adverse clinical outcomes in patients with central PE. METHODS: Large retrospective, observational, and single-center study of hospitalized patients with central PE. Data were gathered on demographics, comorbidities, clinical features on admission, imaging, treatments, and outcomes. Multivariable standard and Least Absolute Shrinkage and Selection Operator (LASSO) machine learning logistic regressions and sensitivity analyses were used to analyze factors associated with a composite of adverse clinical outcomes, including vasopressor use, mechanical ventilation, and inpatient mortality. RESULTS: A total of 654 patients had central PE. The mean age was 63.1 years, 59% were women, and 82% were African American. The composite adverse outcome was observed in 18% (n = 115) of patients. Serum creatinine elevation (odds ratio [OR] = 1.37, 95% CI = 1.20-1.57; p = 0.0001), white blood cell (WBC) count elevation (OR = 1.10, 95% CI = 1.05-1.15; p < 0.001), higher simplified pulmonary embolism severity index (sPESI) score (OR = 1.47, 95% CI = 1.18-1.84; p = 0.001), serum troponin elevation (OR = 1.26, 95% CI 1.02-1.56; p = 0.03), and respiratory rate increase (OR = 1.03, 95% CI = 1.0-1.05; p = 0.02) were independent predictors of adverse clinical outcomes. CONCLUSION: Among patients with central PE, higher sPESI score, WBC count elevation, serum creatinine elevation, serum troponin elevation, and respiratory rate increase were independent predictors of adverse clinical outcomes. Right ventricular dysfunction on imaging and saddle PE location did not predict adverse outcomes.

Clinical characteristics and treatment of patients with central pulmonary embolism and right heart thrombus.

INTRODUCTION: Right heart thrombus (RHT), also known as clot in transit, is an uncommon finding in pulmonary embolism (PE) that is associated with increased inpatient mortality. To date, there is no consensus on the management of RHT. Therefore, we aim to describe the clinical features, treatments, and outcomes of patients with simultaneous RHT and PE. METHODS: This is a retrospective, cross-sectional, and single-center study of hospitalized patients with central PE who had RHT visualized on transthoracic echocardiography (TTE) from January 2012 to May 2022. We use descriptive statistics to describe their clinical features, treatments, and outcomes, including mechanical ventilation, major bleeding, inpatient mortality, length of hospital stay, and recurrent PE on follow-up. RESULTS: Of 433 patients with central PE who underwent TTE, nine patients (2%) had RHT. The median age was 63 years (range 29-87), most were African American (6/9), and females (5/9). All patients had evidence of RV dysfunction and received therapeutic anticoagulation. Eight patients received RHT-directed interventions, including systemic thrombolysis (2/9), catheter-directed suction embolectomy (4/9), and surgical embolectomy (2/9). Regarding outcomes, 4/9 patients were hemodynamically unstable, 8/9 were hypoxemic, and 2/9 were mechanically ventilated. The median length of hospital stay was six days (range 1-16). One patient died during hospital admission, and two patients had recurrent PE. CONCLUSION: We described the different therapeutic approaches and outcomes of patients with RHT treated in our institution. Our study adds valuable information to the literature, as there is no consensus on the treatment of RHT. HIGHLIGHTS: Right heart thrombus (RHT) was a rare finding in central pulmonary embolism. Most patients with RHT had evidence of RV dysfunction and pulmonary hypertension. Most patients received RHT-directed therapies in addition to therapeutic anticoagulation.

Phenotypic screen identifies the natural product silymarin as a novel anti-inflammatory analgesic.

Sensory neuron hyperexcitability is a critical driver of pathological pain and can result from axon damage, inflammation, or neuronal stress. G-protein coupled receptor signaling can induce pain amplification by modulating the activation of Trp-family ionotropic receptors and voltage-gated ion channels. Here, we sought to use calcium imaging to identify novel inhibitors of the intracellular pathways that mediate sensory neuron sensitization and lead to hyperexcitability. We identified a novel stimulus cocktail, consisting of the SSTR2 agonist L-054,264 and the S1PR3 agonist CYM5541, that elicits calcium responses in mouse primary sensory neurons in vitro as well as pain and thermal hypersensitivity in mice in vivo. We screened a library of 906 bioactive compounds and identified 24 hits that reduced calcium flux elicited by L-054,264/CYM5541. Among these hits, silymarin, a natural product derived from milk thistle, strongly reduced activation by the stimulation cocktail, as well as by a distinct inflammatory cocktail containing bradykinin and prostaglandin E2. Silymarin had no effect on sensory neuron excitability at baseline, but reduced calcium flux via Orai channels and downstream mediators of phospholipase C signaling. In vivo, silymarin pretreatment blocked development of adjuvant-mediated thermal hypersensitivity, indicating potential use as an anti-inflammatory analgesic.

An 80-Year-Old Man with Ischemic Heart Disease Who Developed Thrombotic Thrombocytopenic Purpura Following Treatment with Ticagrelor.

BACKGROUND Thrombotic thrombocytopenic purpura (TTP) is associated with widespread microvascular thrombosis, low platelet count, and hemolysis. Ticagrelor is a relatively new agent which functions as a reversible inhibitor of the P2Y12 receptor working to prevent platelet aggregation and is used with or without aspirin in patients with acute coronary syndrome to reduce the risk of myocardial infarction and stroke. We describe the case of an 80-year-old man with ischemic heart disease who developed this rare and potentially fatal adverse reaction known as TTP following treatment with ticagrelor. CASE REPORT We report the case of an 80-year-old man who presented with an acute change in mental status 4 months after initiating ticagrelor following percutaneous coronary intervention. Laboratory testing on presentation revealed evidence of microangiopathic hemolytic anemia, thrombocytopenia, and elevated creatinine levels, suggestive of acute renal failure. The combination of his clinical symptoms and laboratory findings were concerning for TTP, likely secondary to ticagrelor use. The patient was treated with therapeutic plasma exchange, systemic steroids, and hemodialysis, which led to resolution of the hemolysis and recovery of renal function. CONCLUSIONS Although the association between ticagrelor and TTP is rare, early recognition of this life-threatening complication is essential to decrease morbidity and mortality associated with TTP. Since ticagrelor is now more commonly used, it is important that clinicians be aware of this complication.

Coronavirus disease-19 infection and angioedema in African Americans: A case series.

Rationale: Few case series have described the simultaneous development of angioedema in patients with coronavirus 19 disease (COVID-19). Most of these reports were described in at-risk patients for developing bradykinin angioedema. Therefore, we aim to describe 5 African American patients who developed simultaneous COVID-19 and angioedema. Methods: This was a case series of hospitalized patients with simultaneous angioedema and COVID-19 infection in a single center from May 2020 to February 2022. We used descriptive statistics. The study was approved by the institutional review board. Results: Their median age was 55 years (range 28-66); all patients were African American, and 3/5 were males. All patients developed angioedema within a week of hospitalization. Two subjects had prior history of ACEI-related angioedema but were not exposed to ACEI recently, whereas 1 subject was on chronic lisinopril therapy for the last 3 years. All patients had orofacial involvement; the most common locations were lips (5/5) and tongue (3/5). None had histaminergic features of angioedema (either skin rash or peripheral eosinophilia). 4/5 subjects had respiratory symptoms and chest imaging features of COVID-19 pneumonia, whereas 3/5 subjects developed severe COVID-19 infection. Most patients were treated with standard combination of H1 and H2 blockers, and corticosteroids. A total of 2/5 subjects were intubated; one patient developed refractory tongue swelling, received tracheostomy for extubation, and died due to COVID-19 pneumonia. The median length of angioedema improvement was 44 hours (range 20-168 hours). The median length of hospital stay was 15 days (range 1-49). Conclusion: We described 5 cases of angioedema in COVID-19 patients that shared risk factors and features of bradykinin-related angioedema.

Risk factors associated with intubation and readmissions in patients with angioedema: A single-center experience al. / Ann Allergy Asthma Immunol 127 (2021) xxx-xxx"?>.

BACKGROUND: Given the heterogeneity of etiologies, pathophysiology, and presentation of angioedema, variations in clinical outcomes, such as intubation and hospital readmissions, need further clarification. OBJECTIVE: To determine the factors associated with intubation and hospital readmissions in patients with angioedema. METHODS: Retrospective study of patients evaluated with a diagnosis of angioedema in a 6-year period. Demographic and clinical data, such as medication use, family history, comorbidities, and symptoms, were recorded. Multivariable logistic regression was used to analyze factors associated with intubation, whereas Cox regression was used to analyze readmissions. RESULTS: Of 636 patients, the most common cause of angioedema was that induced by angiotensin-converting enzyme inhibitor (ACEI) at 58%. The overall mortality was 0.5%. After adjusting for sex, race, comorbidities, and type of angioedema, smoking (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.10-2.93; P = .02), calcium channel blocker therapy (OR, 1.91; 95% CI, 1.18-3.10; P = .009), histaminergic symptoms (OR, 3.21; 95% CI, 1.93-5.33; P < .001), and age (OR, 1.02; 95% CI, 1.00-1.04; P = .02) were independently associated with increased odds of intubation. Involvement of either the pharynx, larynx, or tongue was associated with higher odds of intubation (OR, 20.96; 95% CI, 10.63-41.33; P < .001). A total of 10% of the patients had a readmission for angioedema within 90 days, and 75% occurred within 30 days. After multivariable Cox regression analysis, only chronic obstructive pulmonary disease and asthma (OR, 2.13; 95% CI, 1.12-4.07; P = .02) and ACEI-related angioedema (OR, 2.93; 95% CI, 1.33-6.47; P = .008) were significantly associated with readmissions. CONCLUSION: Smoking, calcium channel blocker use, histaminergic symptoms, age, and upper airway involvement were markedly associated with intubation. The presence of chronic obstructive pulmonary disease, asthma and ACEI-related angioedema were independently associated with increased odds of readmission.

Metastatic Malignant Struma Ovarii and Graves' Disease: A Rare Occurrence.

OBJECTIVE: Malignant struma ovarii (SO) is a rare condition. Although there have been a few reported cases of malignant SO with coexisting Graves' disease (GD), the exact incidence of metastasis in these cases is not known. We report a rare case of metastatic malignant SO coexisting with GD. METHODS: Clinical examination, pelvic ultrasound, and histopathology of the resected tumor were performed, followed by iodine-131 (I-131) and whole body scan. Antithyroglobulin titers were postoperatively followed. RESULTS: A 43-year-old woman with a history of left ovarian cystic teratoma with SO resected 8 years ago and recently diagnosed GD presented with lower abdominal fullness. Pelvis ultrasound showed a 13.8-cm left adnexal mass, and she underwent left salpingo- oophorectomy. Histology confirmed an intraovarian thyroid tissue housing a highly differentiated follicular thyroid carcinoma, with metastatic peritoneal deposits. She underwent completion surgery and total thyroidectomy. Histology showed no evidence of intrathyroidal malignancy. I-131 therapy was administered, and posttherapeutic I-131 whole body scan revealed a remnant disease. She was started on suppressive levothyroxine therapy and remained clinically well at her 1-year follow-up with downtrending antithyroglobulin titers. CONCLUSION: The coexistence of malignant SO and GD is very rare, and even rarer is the coexistence of metastasis malignant SO and GD. To the best of our knowledge, this is the first reported case of metastatic malignant SO in the setting of GD.

A high-content platform for physiological profiling and unbiased classification of individual neurons.

High-throughput physiological assays lose single-cell resolution, precluding subtype-specific analyses of activation mechanism and drug effects. We demonstrate APPOINT (automated physiological phenotyping of individual neuronal types), a physiological assay platform combining calcium imaging, robotic liquid handling, and automated analysis to generate physiological activation profiles of single neurons at large scale. Using unbiased techniques, we quantify responses to sequential stimuli, enabling subgroup identification by physiology and probing of distinct mechanisms of neuronal activation within subgroups. Using APPOINT, we quantify primary sensory neuron activation by metabotropic receptor agonists and identify potential contributors to pain signaling. We expand the role of neuroimmune interactions by showing that human serum directly activates sensory neurons, elucidating a new potential pain mechanism. Finally, we apply APPOINT to develop a high-throughput, all-optical approach for quantification of activation threshold and pharmacologically validate contributions of ion channel families to optical activation.

Severe Hypothyroxinemia in a Young Adult with Carbimazole-Treated T3-Predominant Graves' Hyperthyroidism, Reversed with L-Thyroxine Loading Immediately Post-Total Thyroidectomy.

Patients with triiodothyronine (T3)-predominant Graves' hyperthyroidism with markedly elevated serum thyroid stimulating immunoglobulin (TSI) levels and massive goitre may display discordant hypothyroxinemia with eutriiodothyroninemia or hypertriiodothyroninemia while on anti-thyroid drug therapy. A 25-year-old female with the above was started on oral carbimazole therapy for 9 months before total thyroidectomy. Preoperatively, her serum free T4 was reduced to below detection limit, and total T4 reduced to 11% of lower limit of normal, while T3 levels remained normal, and TSH remained largely suppressed. Immediately after total-thyroidectomy, a loading dose of L-thyroxine (L-T4) was administered intravenously. She was extubated without any postoperative complications. Serum free and total T4, and TSH normalized within the next 24 hours. The peculiar thyroid axis dynamics and use of L-T4 postoperative loading in such a rare clinical scenario are discussed.

If it is absurd, then why do you do it? The richer the obsessional experience, the more compelling the compulsion.

Mounting evidence suggests that obsessive intrusions are often accompanied and amplified by perceptual experiences of different modalities (e.g., feeling dirt on one's skin while experiencing intrusive thoughts about contamination). Pilot studies conducted online with individuals endorsing mild obsessive-compulsive symptoms have linked the co-occurrence of perceptual experiences and obsessions to the severity of subsequent compulsive behaviour as well as low insight. However, it is presently unclear whether sensory experiences accompany all types of obsessional thoughts or are restricted to certain preoccupations (e.g., contamination and aggression). The present study examined a clinical inpatient and outpatient sample with a formally diagnosed obsessive-compulsive disorder (N = 34). Perceptual properties of intrusive thoughts were assessed with the Sensory Properties of Obsessions Questionnaire. The prevalence of perception-laden obsessive thoughts was comparable with prior studies (73.5%), but the intensity was significantly greater. No association was observed between perceptual experiences and expert-rated insight. However, the severity of perception-laden obsessions predicted the frequency of and impairment associated with compulsive behaviour. This was particularly strong for obsessions about contamination. The present study confirms the high prevalence and clinical relevance of perceptual experiences that accompany obsessions and further challenges the traditional trichotomy splitting mental phenomena into thoughts, intrusions, and hallucinations.

Commonly forgotten complication of Hashimoto's thyroiditis.

Hashimoto's thyroiditis (HT) is a frequently encountered condition in clinical practice and management is generally uncomplicated with patients on a stable dose of thyroxine supplementation. However, complications of thyroid lymphoma can develop, though it is rare and hence commonly forgotten by physicians. We present a case of a patient with HT who developed thyroid lymphoma. A 61-year-old woman presented with an enlarged goitre complicated by compressive symptoms and was diagnosed with HT. She was treated with stable dose of thyroxine but her constitutional symptoms of weight loss prompted further investigations and diagnosis of diffuse large B-cell lymphoma was eventually made. She underwent chemotherapy and adjuvant radiotherapy and is currently in remission 1 year post-treatment. There should be an increased index of suspicion of primary thyroid lymphoma in patients with HT for early diagnosis and treatment for better outcomes.

A Model for Recruiting Clinical Research Participants With Anxiety Disorders in the Absence of Service Provision: Visions, Challenges, and Norms Within a Canadian Context.

High-quality research in clinical psychology often depends on recruiting adequate samples of clinical participants with formally diagnosed difficulties. This challenge is readily met within the context of a large treatment center, but many clinical researchers work in academic settings that do not feature a medical school, hospital connections, or an in-house clinic. This article describes the model we developed at the University of Waterloo Centre for Mental Health Research for identifying and recruiting large samples of people from local communities with diagnosable mental health problems who are willing to participate in research but for whom treatment services are not offered. We compare the diagnostic composition, symptom profile, and demographic characteristics of our participants with treatment-seeking samples recruited from large Canadian and American treatment centers. We conclude that the Anxiety Studies Division model represents a viable and valuable method for recruiting clinical participants from the community for psychopathology research.

A false sense of security: safety behaviors erode objective speech performance in individuals with social anxiety disorder.

In the current study, 55 participants with a diagnosis of generalized social anxiety disorder (SAD), 23 participants with a diagnosis of an anxiety disorder other than SAD with no comorbid SAD, and 50 healthy controls completed a speech task as well as self-reported measures of safety behavior use. Speeches were videotaped and coded for global and specific indicators of performance by two raters who were blind to participants' diagnostic status. Results suggested that the objective performance of people with SAD was poorer than that of both control groups, who did not differ from each other. Moreover, self-reported use of safety behaviors during the speech strongly mediated the relationship between diagnostic group and observers' performance ratings. These results are consistent with contemporary cognitive-behavioral and interpersonal models of SAD and suggest that socially anxious individuals' performance skills may be undermined by the use of safety behaviors. These data provide further support for recommendations from previous studies that the elimination of safety behaviors ought to be a priority in cognitive behavioral therapy for SAD.

Self-portrayal concerns and their relation to safety behaviors and negative affect in social anxiety disorder.

It has been proposed that self-portrayal concerns - fundamental worries that particular negative self-attributes will become exposed during social encounters and criticized by others - underlie the experience of social anxiety (SA) and drive associated avoidance and safety behaviors (Moscovitch, 2009). The development of the Negative Self Portrayal Scale (NSPS) to assess such concerns across the dimensions of social competence, signs of anxiety, and physical appearance has helped yield promising initial findings that support the basic tenets of Moscovitch's (2009) theoretical model in samples of undergraduate students (Moscovitch & Huyder, 2011). The present study investigated the nature of self-portrayal concerns and their relation to affect and behavior in a sample of 194 community-based participants consisting of (a) 62 individuals with a principal diagnosis of generalized SAD, either with (n = 35) or without (n = 27) an additional depressive disorder diagnosis, (b) 51 individuals with another principal anxiety disorder diagnosis, either with (n = 22) or without (n = 29) an additional diagnosis of SAD, and (c) 81 healthy controls. Participants completed trait questionnaires, daily diaries of naturalistic social encounters, and a laboratory-based speech task. Results demonstrated (a) that a diagnosis of SAD confers unique risk for elevated self-portrayal concerns, (b) that such concerns predict significant variance in safety behavior use across diverse contexts, and (c) that the use of safety behaviors mediates the relation between such concerns and the experience of heightened negative affect. Implications for case conceptualization and treatment of SAD are discussed.