Multiple-Choice versus Open-Ended Questions in Advanced Clinical Neuroanatomy: Using a National Neuroanatomy Assessment to Investigate Variability in Performance Using Different Question Types.

Methods of assessment in anatomy vary across medical schools in the United Kingdom (UK) and beyond; common methods include written, spotter, and oral assessment. However, there is limited research evaluating these methods in regards to student performance and perception. The National Undergraduate Neuroanatomy Competition (NUNC) is held annually for medical students throughout the UK. Prior to 2017, the competition asked open-ended questions (OEQ) in the anatomy spotter examination, and in subsequent years also asked single best answer (SBA) questions. The aim of this study is to assess medical students' performance on, and perception of, SBA and OEQ methods of assessment in a spotter style anatomy examination. Student examination performance was compared between OEQ (2013-2016) and SBA (2017-2020) for overall score and each neuroanatomical subtopic. Additionally, a questionnaire explored students' perceptions of SBAs. A total of 631 students attended the NUNC in the studied period. The average mark was significantly higher in SBAs compared to OEQs (60.6% vs. 43.1%, P < 0.0001)-this was true for all neuroanatomical subtopics except the cerebellum. Students felt that they performed better on SBA than OEQs, and diencephalon was felt to be the most difficult neuroanatomical subtopic (n = 38, 34.8%). Students perceived SBA questions to be easier than OEQs and performed significantly better on them in a neuroanatomical spotter examination. Further work is needed to ascertain whether this result is replicable throughout anatomy education.

Reduced RVSWI Is Associated With Increased Mortality in Connective Tissue Disease Associated Pulmonary Arterial Hypertension.

Rationale: The prognosis of pulmonary arterial hypertension is poor, especially amongst patients with connective tissue disease related pulmonary arterial hypertension. Right ventricular contractility is known to be decreased in scleroderma related pulmonary arterial hypertension. However, it is not known whether intrinsic right ventricular dysfunction is seen in a general CTD population. Objectives: In this study of a large cohort of patients with pulmonary arterial hypertension with multi-year follow-up, we sought to examine the association of measurements of right ventricular function with survival in connective tissue disease associated pulmonary arterial hypertension. Methods: Clinical characteristics of a deidentified cohort of 845 patients with pulmonary arterial hypertension were compared between patients with and without connective tissue disease. The Kaplan-Meier method was used to examine the survival of patients over more than 4 years. The association between right ventricular stroke work index and mortality was examined in patients with connective tissue disease associated pulmonary arterial hypertension. Measurements and Main Results: Significant differences in the 6-min walk distance, Borg dyspnea index, right ventricular stroke work index, and pulmonary artery pulsatility index were identified between patients with and without connective tissue disease associated pulmonary arterial hypertension. Patients with connective tissue disease had a lower right ventricular stroke work index, which was associated with decreased survival in this group; this association approached significance when adjusting for age and renal function. Conclusions: Right ventricular dysfunction as measured by right ventricular stroke work index is associated with decreased survival in patients with connective tissue disease associated pulmonary arterial hypertension despite similar pulmonary vascular resistance. These findings are suggestive of intrinsic right ventricular function in connective tissue disease associated pulmonary arterial hypertension that has a negative impact on the long-term survival of these individuals.

Primary cardiac hospitalizations in pulmonary arterial hypertension: Trends and outcomes from 2001 to 2014.

BACKGROUND: Hospitalizations in pulmonary arterial hypertension (PAH) are common and are often for cardiac conditions. Using the National (Nationwide) Inpatient Sample (NIS), we examined characteristics and mortality of primary cardiac hospitalizations in PAH from 2001 to 2014. METHODS: Adult hospitalizations with any diagnosis code for PAH were identified. Primary cardiac disease was defined as a primary discharge diagnosis of congestive heart failure (CHF), pulmonary heart disease, coronary atherosclerosis, acute myocardial infarction, dysrhythmia, conduction disorder, cardiomyopathy or carditis, heart valve disorder, or cardiac arrest. Temporal trends, characteristics, and in-hospital mortality were analyzed. RESULTS: From 2001 to 2014, there were 207,095 hospitalizations in PAH, of which 100,509 (48.5%) carried a primary cardiac diagnosis. Most primary cardiac hospitalizations in PAH were for CHF, and pneumonia was the most common primary non-cardiac diagnosis. Over the study period, primary cardiac hospitalizations in PAH fell from 52.9% to 41.4% (p < 0.001). CHF was the most frequent primary cardiac diagnosis associated with death, with sepsis representing the most common primary non-cardiac disease (1,226; 25.0%). Overall, the mortality in primary cardiac hospitalizations in PAH was 5.3% (vs. in primary non-cardiac, 6.9%, p < 0.001). On multivariable analysis, a primary cardiac discharge diagnosis remained associated with a decreased risk of death (odds ratio 0.85, p = 0.010). CONCLUSION: Primary cardiac hospitalizations in PAH are common and are associated with decreased mortality compared to admissions for primary non-cardiac diagnoses.

Precise finger somatotopy revealed by focal motor cortex injury.

BACKGROUND: Somatotopy is considered the hallmark of the primary motor cortex. While this is fundamentally true for the major body parts (head, upper and lower extremities), evidence supporting the existence of within-limb somatotopy is scarce. METHOD: We report a young man presenting recurrent ischemic strokes with selective finger weakness in whom serial motor cortex mapping procedures were performed. RESULT: Following the first stroke, which largely spared the motor cortex, motor mapping displayed overlap of the motor representations of the hand muscles. The second focal stroke, affecting the lateral part of the hand knob, resulted in selective loss of the first dorsal interosseous muscle motor evoked potentials while sparing those of the adductor digiti minimi muscle. This observation is in apparent contradiction with the first mapping results that suggested complete overlap of motor representations. DISCUSSION: Our mapping results provide evidence for the existence of very precise within-limb somatotopy and confirm the proposed homuncular order, whereby lateral fingers are represented laterally and medial fingers medially. The discrepancy between the initial and subsequent mapping results is discussed in light of functional organization of the primary motor cortex.

Hospitalizations with hereditary hemorrhagic telangiectasia and pulmonary hypertension in the United States from 2000 to 2014.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease that causes widespread abnormal vasculature development, resulting in multiple complications including pulmonary hypertension (PH). Despite the potential severity of PH, there is a lack of data on hospitalization characteristics and outcomes in the HHT-PH population. The purpose of this analysis was to describe trends and outcomes of HHT-PH hospitalizations within the National (Nationwide) Inpatient Sample (NIS). METHODS: Adult hospitalizations (age ≥18 years) with a principal or secondary diagnosis of HHT were identified from the 2000-2014 NIS. Records were stratified by a concurrent PH diagnosis. Trends, characteristics, and outcomes of hospitalizations with HHT and PH were analyzed. RESULTS: There were 55,189 adult hospitalizations with HHT from 2000 to 2014, of which 4602 (8.3%) had a concurrent diagnosis of PH. HHT-PH hospitalizations rose steadily from 165 (5.1%) in 2000 to 540 (13.8%) in 2014 (p < 0.001). They were more common in females (vs. HHT without PH, 71.6% vs. 59.2%, p < 0.001) and were associated with a higher comorbidity burden (total 4.0 ±â€¯0.1 vs. 2.4 ±â€¯0.03, p < 0.001). Inpatient mortality was higher in HHT-PH hospitalizations than in HHT without PH (3.5% vs. 1.8%, p < 0.001). On multivariable logistic regression, the diagnosis of PH remained significantly associated with a higher risk of inpatient death (odds ratio 1.71, 95% confidence interval 1.11-2.63, p = 0.015) in HHT hospitalizations. CONCLUSIONS: HHT-PH hospitalizations rose from 2000 to 2014. Notably, HHT patients with a concurrent PH diagnosis were at significantly higher risk of in-hospital mortality.

Statin therapy associated with improved thrombus resolution in patients with deep vein thrombosis.

OBJECTIVE: Statin therapy has been associated with a decreased incidence of venous thromboembolism (VTE) in clinical trials and enhanced thrombus resolution in animal models. The effect of statins on thrombus resolution has not been reported clinically. This study investigates the association of statins with thrombus resolution or improvement in patients with deep venous thrombosis (DVT). METHODS: A retrospective study of the electronic medical records of consecutive adult patients presenting with lower extremity DVT was performed. Patients were divided into two groups based on statin therapy (statin group) or lack thereof (nonstatin group). The two groups were compared with respect to demographics, comorbidities, and risk factors for VTE. Initial as well as all subsequent ultrasound reports were reviewed for each patient to determine extent of DVT and subsequent change in thrombus characteristics. Long-term outcomes examined were mortality, VTE recurrence, and thrombus improvement or resolution on follow-up ultrasound examination. Multivariable analysis was used to determine independent predictors of thrombus resolution or improvement, VTE recurrence, and mortality. RESULTS: A total of 818 patients with DVT were identified (statin group, n = 279 [34%]; nonstatin group, n = 539 [66%]). The patients in the statin group were significantly older (P < .001). Patients on statins were more likely to have risk factors for and manifestations of atherosclerosis and to be on antiplatelet therapy (P < .001), whereas those in the nonstatin group were more likely to have a hypercoagulable disorder (P = .009) or prior DVT (P = .033). There was no significant difference in provoked DVT, extent of DVT, or association with pulmonary embolism (PE), but patients on statins were more likely to have high-risk PE (P = .046). There was no difference in patients receiving anticoagulation, type and duration of anticoagulation, inferior vena cava filter placement, or treatment with lytic therapy. There was no difference in thrombus resolution, mortality, or recurrence of DVT, PE, or VTE between the groups. On multivariable analysis, age, proximal DVT, CAD, and cancer were associated with higher mortality, whereas anticoagulation with coumadin and direct oral anticoagulants and antiplatelet therapy were associated with lower mortality. Statin therapy, antiplatelet therapy, and younger age were associated with thrombus resolution or improvement. CONCLUSIONS: Statin therapy is associated with greater thrombus resolution or improvement in patients with DVT. However, statin therapy in this study was not associated with different clinical outcomes of VTE recurrence or mortality.

Hypercoagulability in Pulmonary Hypertension.

Pulmonary hypertension (PH) is divided into varied pathophysiological and etiologic groupings, as classified by the World Health Organization (WHO). Pulmonary arterial hypertension (PAH), which falls under WHO group 1 PH, is a progressive and potentially fatal disease characterized by a vasoconstrictive, proliferative, and thrombotic phenotype, which leads to increased pulmonary artery pressure, right heart failure, and death. Pathologically, in situ thromboses are found in the small distal pulmonary arteries. Dysregulation of coagulation, platelet function, and endothelial cells may contribute to a prothrombotic state. There is mixed evidence for the use of anticoagulation or antiplatelet therapy in PAH patients.

Chronic Right Heart Failure: Expanding Prevalence and Challenges in Outpatient Management.

Right heart failure is caused by right heart dysfunction resulting in suboptimal stroke volume to supply the pulmonary circulation. Therapeutic developments mean that patients with acute right heart failure survive to hospital discharge and live with chronic right heart failure. Chronic right heart failure management aims to reduce afterload, optimize preload, and support contractility, with the best evidence available in vascular targeted therapy for pulmonary arterial hypertension. However, the management of chronic right heart failure relies on adapting therapies for left ventricular heart failure to the right. We review right heart failure management in the ambulatory setting and its challenges.

Endovascular Treatment of a Large Iliac Vein Aneurysm and High-Flow Arteriovenous Fistula.

Aneurysms associated with arteriovenous fistulas (AVFs) are rare but can cause significant morbidity. They are often diagnosed after rupture, pain, or embolization. We describe a unique case of a 35-year-old woman with a large iliac vein aneurysm related to an acquired AVF incidentally discovered on ultrasound during pregnancy. She had a diagnosis of "idiopathic" pulmonary hypertension for several years. This report details the diagnosis and treatment with an arterial stent graft that was effective in decreasing the size of the venous aneurysm and reversing the systemic changes associated with the disease.

Is hyponatremia associated with mortality in pulmonary arterial hypertension?

Hyponatremia is associated with poor prognosis in left heart failure and liver disease. Its prognostic role in pulmonary arterial hypertension (PAH) is not well defined. We investigated the association between hyponatremia and one-year mortality in two large cohorts of PAH. This study is a secondary analysis evaluating the association between hyponatremia and one-year mortality in patients treated with subcutaneous treprostinil (cohort 1). The results are validated using a PAH registry at a tertiary referral center (cohort 2). Eight-hundred and twenty patients were enrolled in cohort 1 (mean age = 47 ± 14 years) and 791 in cohort 2 (mean age = 55 ± 15 years). Sodium level is negatively correlated with mean right atrial pressure (r = -0.09, P = 0.018; r = -0.089, P = 0.015 in cohorts 1 and 2, respectively). In unadjusted analyses of cohort 1, the sodium level (as a continuous variable) is associated with one-year mortality (hazard ratio = 0.94; P = 0.035). Hyponatremia loses its significance (as a continuous variable and when dichotomized at ≤ 137 mmol/L; P = 0.12) when adjusted for functional class (FC), which is identified as the variable whose presence turns the effect of sodium level into non-significant. Secondary analyses using a cut-off value of < 135 mmol/L showed similar results. These results are validated in cohort 2. Although the sample size for patients with sodium < 130 mmol/L is small (n = 31), severe hyponatremia is associated with higher overall mortality (47% versus 23%; P = 0.01), even when adjusting for age, FC, and baseline 6-min walk distance ( P < 0.001). Although baseline hyponatremia is associated with one-year mortality, it loses its significance when adjusted for FC.

S100A12 as a marker of worse cardiac output and mortality in pulmonary hypertension.

BACKGROUND AND OBJECTIVE: Molecular biomarkers are needed to refine prognostication and phenotyping of pulmonary hypertension (PH) patients. S100A12 is an emerging biomarker of various inflammatory diseases. This study aims to determine the prognostic value of S100A12 in PH. METHODS: Exploratory microarray analysis performed on peripheral blood mononuclear cells (PBMC) collected from idiopathic pulmonary fibrosis (IPF) patients suggested an association between S100A12 and both PH and mortality. So the current study was designed to evaluate for an association between S100A12 in peripheral blood collected from two well-phenotyped PH cohorts in two other centres to derive and validate an association between S100A12 protein serum concentrations and mortality. RESULTS: The majority of the patients in the discovery and validation cohorts were either World Health Organization (WHO) group 1 (pulmonary arterial hypertension (PAH)) or 3 (lung disease-associated) PH. In the discovery PH cohort, S100A12 was significantly increased in patients with PH (n = 51) compared to controls (n = 22) (29.8 vs 15.7 ng/mL, P < 0.001) and negatively correlated with cardiac output (r = -0.58, P < 0.001) in PH patients. When S100A12 data were pooled from both cohorts, PAH and non-PAH PH patients had higher S100A12 compared to healthy external controls (32.6, 30.9, 15.7 ng/mL; P < 0.001). S100A12 was associated with an increased risk in overall mortality in PH patients in both the discovery (n = 51; P = 0.008) and validation (n = 40; P < 0.001) cohorts. CONCLUSION: S100A12 levels are increased in PH patients and are associated with increased mortality.

Pulmonary hypertension in patients with interstitial lung disease.

Interstitial lung diseases (ILDs) comprise a broad and heterogeneous group of more than two hundred diseases with common functional characteristics. Their diagnosis and management require a multidisciplinary approach. This multidisciplinary approach involves the assessment of comorbid conditions including pulmonary hypertension (PH) that exerts a dramatic impact on survival. The current World Health Organization (WHO) classification of PH encompasses many of the interstitial lung diseases into WHO Group 3, while sarcoidosis, Pulmonary Langerhans Cell Histiocytosis and lymphangioleiomyomatosis are placed into WHO Group 5 as diseases with unclear or multifactorial mechanisms. Connective tissue diseases could span any of the 5 WHO groups based on the primary phenotype into which they manifest. Interestingly, several challenging phenotypes present with features that overlap between two or more WHO PH groups. Currently, PH-specific treatment is recommended only for patients classified into WHO Group 1 PH. The lack of specific treatment for other groups, including PH in the setting of ILD, reflects the poor outcomes of these patients. Thus, identification of the optimal strategy for ILD patients with PH remains an amenable need. This review article provides a brief overview of biomarkers indicative of vascular remodeling in interstitial lung disease, summarizes the current state of knowledge regarding patients with PH and ILD and highlights future perspectives that remain to be addressed.

Pulmonary arterial hypertension in the setting of scleroderma is different than in the setting of lupus: A review.

Pulmonary hypertension (PH) is a clinical syndrome that is subdivided into five groups per the World Health Organization (WHO) classification, based largely on hemodynamic and pathophysiologic criteria. WHO Group 1 PH, termed pulmonary arterial hypertension (PAH), is a clinically progressive disease that can eventually lead to right heart failure and death, and it is hemodynamically characterized by pre-capillary PH and increased pulmonary vascular resistance in the absence of elevated left ventricular filling pressures. PAH can be idiopathic, heritable, or associated with a variety of conditions. Connective tissue diseases make up the largest portion of these associated conditions, most commonly systemic sclerosis (SSc), followed by mixed connective tissue disease and systemic lupus erythematous. These etiologies (namely SSc and Lupus) have been grouped together as connective tissue disease-associated PAH, however emerging evidence suggests they differ in pathogenesis, clinical course, prognosis, and treatment response. This review highlights the differences between SSc-PAH and Lupus-PAH. After introducing the diagnosis, screening, and pathobiology of PAH, we discuss connective tissue disease-associated PAH as a group, and then explore SSc-PAH and SLE-PAH separately, comparing these 2 PAH etiologies.

Mitochondrial dysfunction and pulmonary hypertension: cause, effect, or both.

Pulmonary hypertension describes a heterogeneous disease defined by increased pulmonary artery pressures, and progressive increase in pulmonary vascular resistance due to pathologic remodeling of the pulmonary vasculature involving pulmonary endothelial cells, pericytes, and smooth muscle cells. This process occurs under various conditions, and although these populations vary, the clinical manifestations are the same: progressive dyspnea, increases in right ventricular (RV) afterload and dysfunction, RV-pulmonary artery uncoupling, and right-sided heart failure with systemic circulatory collapse. The overall estimated 5-yr survival rate is 72% in highly functioning patients, and as low as 28% for those presenting with advanced symptoms. Metabolic theories have been suggested as underlying the pathogenesis of pulmonary hypertension with growing evidence of the role of mitochondrial dysfunction involving the major proteins of the electron transport chain, redox-related enzymes, regulators of the proton gradient and calcium homeostasis, regulators of apoptosis, and mitophagy. There remain more studies needed to characterize mitochondrial dysfunction leading to impaired vascular relaxation, increase proliferation, and failure of regulatory mechanisms. The effects on endothelial cells and resulting interactions with their microenvironment remain uncharted territory for future discovery. Additionally, on the basis of observations that the "plexigenic lesions" of pulmonary hypertension resemble the unregulated proliferation of tumor cells, similarities between cancer pathobiology and pulmonary hypertension have been drawn, suggesting interactions between mitochondria and angiogenesis. Recently, mitochondria targeting has become feasible, which may yield new therapeutic strategies. We present a state-of-the-art review of the role of mitochondria in both the pathobiology of pulmonary hypertension and potential therapeutic targets in pulmonary vascular processes.

Risk factors for presence and severity of pulmonary embolism in patients with deep venous thrombosis.

OBJECTIVE: The Caprini model estimates patients' risk for venous thromboembolism by 30 different factors. Hemodynamically significant pulmonary embolism (PE), defined as high-risk (massive) or intermediate-risk (submassive) PE, has high morbidity and mortality rates. This study tests whether the Caprini model and deep venous thrombosis (DVT) characteristics correlate with the prevalence of PE and hemodynamically significant PE in patients with DVT. METHODS: A retrospective review of patients diagnosed with DVT between January 2013 and August 2014 in a tertiary care center was performed. Multivariable analysis was used to determine predictors of PE and hemodynamically significant PE. RESULTS: Of 838 consecutive patients with DVT, 217 (25.9%) had concomitant PE at presentation, of whom 135 had hemodynamically significant PE (101 submassive PE, 34 massive PE). The mean age was 65 years, and 51.0% were women. There was no significant relation between age or gender and the occurrence of PE or hemodynamically significant PE. Patients with PE were less likely to have undergone recent surgery (18.4% vs 30.3%; P = .001), to have sepsis (4.6% vs 11.8%; P = .002), and to have higher Caprini scores (6.1 vs 6.5; P = .047). Patients with DVT were less likely to have hemodynamically significant PE after recent surgery (13.3% vs 27.2%; P = .011) but more likely to have hemodynamically significant PE with proximal DVT (80.7% vs 64.2%). There was no association between Caprini score and hemodynamically significant PE (6.3 vs 5.7; P = .171). CONCLUSIONS: The Caprini model has a poor association with PE or hemodynamically significant PE in patients with DVT. Among all patients with DVT, a concomitant diagnosis of PE or hemodynamically significant PE is less common in those with sepsis or undergoing recent surgery but more common in those with proximal DVT.

A 49-Year-Old Man with Subacute Respiratory Failure and Interstitial Lung Opacities.

BACKGROUND Pulmonary arterial hypertension (PAH) results from proliferative vasculopathy involving all layers of the blood vessel. Similar findings may be present in pulmonary hypertension (PH) associated with microscopic tumor embolism, which are thought to be related to the phenomenon of pulmonary tumor thrombotic microangiopathy (PTTM). PTTM is associated with the activation of the coagulation system at the surface of the tumor emboli, resulting in stenosis or occlusion of the vessel. CASE REPORT A 49-year-old man with stage IV gastro-esophageal junction adenocarcinoma presented with complaints of cough and shortness of breath. These symptoms coincided with the initiation of trastuzumab with a new experimental medication with receptor tyrosine kinase blocking activity. A trans-thoracic echocardiogram demonstrated severely increased right ventricle (RV) cavity size with severely decreased RV systolic function. A computed tomography angiography was negative for pulmonary embolism but demonstrated new bilateral pulmonary infiltrates. Bronchoalveolar lavage ruled out an infectious etiology. Trans-bronchial biopsies (TBBx) showed arteriole obliteration by smooth muscle proliferation suggestive of pulmonary vasculopathy. The right heart catheterization (RHC) confirmed severe pulmonary hypertension. Unfortunately, shortly after the RHC, the patient developed pulseless electrical activity cardiac arrest and died. Autopsy results were similar to those of the TBBx, except for diffuse dissemination of tumor cells in the lymphatic channels and small pulmonary vessels, confirming a diagnosis of PTTM. CONCLUSIONS We highlight the limitations of trans-bronchial biopsies in evaluating PTTM. The final diagnosis of PTTM was not made until the autopsy was done.