Late-Onset Hemorrhagic Pericardial Effusion and Cardiac Tamponade Associated With Immune Checkpoint Inhibitors: Case Report and Literature Review.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target T lymphocytes and stimulate the immune system. However, the use of ICIs is associated with immune-related adverse events (irAEs). Pericardial disease is a cardiovascular irAEs that can present as cardiac tamponade. The precise mechanisms underlying pericardial complications are not fully understood. Late-onset hemorrhagic pericardial effusion associated with ICIs is quite rare; the mechanism and predisposing factors are yet to be determined. This case report describes a patient with diffuse large B-cell lymphoma (DLBCL) who received pembrolizumab for 390 days and subsequently developed cardiac tamponade caused by hemorrhagic pericardial effusion. The purpose of this report is to raise awareness about the occurrence of late-onset cardiac tamponade and provide a summary of available data on patients who experienced hemorrhagic pericardial effusion during ICI treatment.

Cardiorespiratory Insufficiency and Performance Fatigability in Women with Systemic Lupus Erythematosus.

Purpose: Patients with systemic lupus erythematosus (SLE) experience excessive, debilitating fatigue with previously reported evidence of etiologically mediated cardiorespiratory impairments. Performance fatigability provides a precise characterization of fatigue as it can be quantified objectively as a function of time, frequency, and/or duration. Nevertheless, little consideration has been given to understanding performance fatigability and its physiological determinants in those with SLE. The purpose of this study was to characterize performance fatigability in patients with SLE, utilizing measures surrounding the anaerobic threshold, with emphasis on cardiorespiratory impairment as a potential mediating factor. Methods: This was a case-control study design. 44 physically inactive women, 26 with SLE and 18 controls, completed a treadmill cardiopulmonary exercise test to volitional exhaustion. Results: There were no significant differences in age (SLE 34.8(9.0) vs Control 36.9(7.3) yrs; p=0.422) between groups. BMI (SLE 27.1(5.4) vs Control 23.8(5.2) kg/m2; p=0.045) was significantly higher in the SLE vs Control group. Resting heart rate (SLE 68(16) vs Control 78(15) bpm; p=0.040) was significantly lower in the SLE compared to the Control group. The VO2 corresponding to the anaerobic threshold (AT-VO2), used to identify the onset of exercise-induced fatigue, was significantly lower in women with SLE than in controls (SLE 12.4(3.1) vs Control 16.4(2.2) ml/kg/min; p<0.001), as was AT-stage (SLE 2.5(0.90) vs Control 3.4(0.78); p=0.002). Additionally, Fatigue Severity Score (FSS) was highly and inversely correlated with AT-VO2 (rho=-0.615; p<0.001) and FSS was highly correlated with Functional Aerobic Impairment Index (FAI; rho=0.663; p<0.001). Conclusion: This study underscores severe performance fatigability in patients with SLE and its link to cardiorespiratory insufficiency. Physiological presentation of performance fatigability was observed during very low intensities of exercise, emphasizing the negative impact it may have on physical function in this population.

Altered functional neuronal activity in neuropsychiatric lupus: A systematic review of the fMRI investigations.

OBJECTIVE: Recent years have seen a rapid increase in the investigation of neuropsychiatric lupus (NPSLE) through the use of functional magnetic resonance imaging (fMRI). Measuring specific neuronal activity in regional brain structures during a cognitive task may identify possible biomarker for NPSLE. METHODS: A systematic review of fMRI studies of systemic lupus erythematosus (SLE) is carried out to address common findings that characterize NPSLE. RESULTS: A disturbance to the working memory and executive function brain regions is among the most well-replicated finding. Differences in brain activation may relate to an early primary dysfunction of these regions. Increased functional connectivity strength in the fronto-parietal cortex in the resting state is correlated with SLE disease activity in one study. Decrease functional connectivity is observed in lupus patients with long-term disease. However, there is strong evidence that points toward a lack of effective integration of distributed functional brain regions and disruptions in the subtle modulation of brain function in relation to task demands in SLE. Limitations of the literature to date include the use of small sample size and the lack of addressing the effect of confounding variables, including immunosuppressive treatment. CONCLUSION: Careful definitions of the fMRI technique used both in the design, analyses, and interpretation of high dimensional data is needed, when dealing with a limited number of SLE subjects with heterogeneous manifestations and unknown pathophysiology.

Exploratory study on oxygen consumption on-kinetics during treadmill walking in women with systemic lupus erythematosus.

OBJECTIVE: To determine whether oxygen consumption (V o(2)) on-kinetics differed between groups of women with systemic lupus erythematosus (SLE) and sedentary but otherwise healthy controls. DESIGN: Exploratory case-control study. SETTING: Medical school exercise physiology laboratory. PARTICIPANTS: Convenience samples of women with SLE (n=12) and sedentary but otherwise healthy controls (n=10). INTERVENTION: None. MAIN OUTCOME MEASURES: V o(2) on-kinetics indices including time to steady state, rate constant, mean response time (MRT), transition constant, and oxygen deficit measured during bouts of treadmill walking at intensities of 3 and 5 metabolic equivalents (METs). RESULTS: Time to steady state and oxygen deficit were increased and rate constant was decreased in the women with SLE compared with controls. At the 5-MET energy demand, the transition constant was lower and MRT was longer in the women with SLE than in controls. For a similar relative energy expenditure that was slightly lower than the anaerobic threshold, the transition constant was higher in controls than in women with SLE. CONCLUSION: V o(2) on-kinetics was prolonged in women with SLE. The prolongation was concomitant with an increase in oxygen deficit and may underlie performance fatigability in women with SLE.

Proposed response criteria for neurocognitive impairment in systemic lupus erythematosus clinical trials.

The objective of this study was to identify reliable and valid instruments to measure cognitive impairment in systemic lupus erythematosus (SLE), and to define minimally important change of cognitive impairment in SLE for clinical trials. Neurocognitive measures used in randomized clinical trials in SLE were reviewed, and response criteria were developed using consensus expert opinion. The definition of cognitive impairment in the ACR nomenclature for neuropsychiatric lupus syndrome was adopted. Cognitive impairment is a deficit of 2.0 or more standard deviations (SD) below the mean, compared to normative data, in the key domains of attention, memory and psychomotor speed. Cognitive decline is defined as a deficit of 1.5-1.9 SD below the mean. Focal decline is defined if impairment exists in one or more measures within one domain, and multifocal decline if impairment exists on measures spanning two or more domains. The combination of ACR neuropsychological battery and the Cognitive Symptoms Inventory (CSI) is recommended to quantitate cognitive function. A clinically important response is defined as an improvement of > or = 1.0 SD with an effect size of 1.0 in the key domains of the ACR neuropsychological testing, and an improvement of > or = 1.0 SD with an effect size of 1.0 in functional performance of the CSI.

Anticoagulation strategies for treatment of ischemic stroke and antiphospholipid syndrome: case report and review of the literature.

A 49-year-old Caucasian man with antiphospholipid syndrome who experienced an ischemic stroke required multidisciplinary decisions regarding acute and long-term care. The patient first received warfarin and unfractionated heparin, followed by low-molecular-weight heparin. However, he developed complications from these drugs (warfarin-induced necrosis and heparin-induced thrombocytopenia), resulting in thigh necrosis and multiple additional cerebral and peripheral infarcts. His condition improved after warfarin and the heparins were discontinued, and a direct thrombin inhibitor, argatroban, was given intravenously for acute treatment. Argatroban is the only anticoagulant known to be safe in patients who experience an acute ischemic stroke in the setting of heparin-induced thrombocytopenia. For long-term anticoagulation, fondaparinux, an indirect, selective factor Xa inhibitor, was given subcutaneously. The patient received intravenous dexamethasone, later changed to azathioprine, for immunomodulatory treatment. He had significant improvement in his neurologic deficits without recurrent events over the next 18 months. Management of anticoagulation therapy in patients with antiphospholipid syndrome is complex and challenging, and therapeutic strategies need to be evaluated further.