Common and Dissociable Dysfunction of the Reward System in Bipolar and Unipolar Depression

Unipolar and bipolar depressive episodes have a similar clinical presentation that suggests common dysfunction of the brain’s reward system. Here, we evaluated the relationship of both dimensional depression severity and diagnostic category to reward system function in both bipolar and unipolar depression. In total, 89 adults were included, including 27 with bipolar depression, 25 with unipolar depression, and 37 healthy comparison subjects. Subjects completed both a monetary reward task and a resting-state acquisition during 3T BOLD fMRI. Across disorders, depression severity was significantly associated with reduced activation for wins compared with losses in bilateral ventral striatum, anterior cingulate cortex, posterior cingulate cortex, and right anterior insula. Resting-state connectivity within this reward network was also diminished in proportion to depression severity, most notably connectivity strength in the left ventral striatum. In addition, there were categorical differences between patient groups: resting-state connectivity at multiple reward network nodes was higher in bipolar than in unipolar depression. Reduced reward system task activation and resting-state connectivity therefore appear to be a brain phenotype that is dimensionally related to depression severity in both bipolar and unipolar depression. In contrast, categorical differences in reward system resting connectivity between unipolar and bipolar depression may reflect differential risk of mania. Reward system dysfunction thus represents a common brain mechanism with relevance that spans categories of psychiatric diagnosis.     

Acute liver injury in COVID-19 patients hospitalized in the intensive care unit: Narrative review

In recent years, humanity has been confronted with a global pandemic due to coronavirus disease 2019 (COVID-19), which has caused an unprecedented health and economic crisis worldwide. Apart from the respiratory symptoms, which are considered the principal manifestations of COVID-19, it has been recognized that COVID-19 constitutes a systemic inflammatory process affecting multiple organ systems. Across the spectrum of organ involvement in COVID-19, acute liver injury (ALI) has been gradually gaining increasing attention by the international scientific community. COVID-19 associated liver impairment can affect a considerable proportion of COVID-19 patients and seems to correlate with the severity of the disease course. Indeed, COVID-19 patients hospitalized in the intensive care unit (ICU) run a greater risk of developing ALI due to the severity of their clinical condition and in the context of multi-organ failure. The putative pathophysiological mechanisms of COVID-19 induced ALI in ICU patients remain poorly understood and appear to be multifactorial in nature. Several theories have been proposed to explain the occurrence of ALI in the ICU setting, such as hypoperfusion and ischemia due to hemodynamic instability, passive liver congestion as a result of congestive heart failure, ischemia-reperfusion injury, hypoxia due to respiratory failure, mechanical ventilation itself, sepsis and septic shock, cytokine storm, endotheliitis with concomitant coagulopathy, drug-induced liver injury, parenteral nutrition and direct cytopathic viral effect. It should be noted that no specific therapy for COVID-19 induced ALI exists. Therefore, the therapeutic approach lies in preventive measures and is exclusively supportive once ALI ensues. The aim of the current review is to scrutinize the existing evidence on COVID-19 associated ALI in ICU patients, explore its clinical implications, shed light on the underlying pathophysiological mechanisms and propose potential therapeutic approaches. Ongoing research on the particular scientific field will further elucidate the pathophysiology behind ALI and address unresolved issues, in the hope of mitigating the tremendous health consequences imposed by COVID-19 on ICU patients.     

Modifiable Failures in the Colorectal Cancer Screening Process and Their Association With Risk of Death

1. Download high-res image (240KB)
2. Download full-size image

     

Quantitative measures for assessing rheumatoid arthritis in clinical trials and clinical care

There is no single 'gold standard' quantitative measure to assess and monitor the clinical status in patients with rheumatoid arthritis (RA). Therefore, a variety of measures have been used in clinical research and clinical care, including laboratory tests, radiographic scores, formal joint counts, physical measures of functional status, global measures and patient self-report questionnaires. These measures may address disease activity, joint damage, both activity and damage, or long-term outcomes. Measures of disease activity, such as joint swelling, are reversible and are emphasized in clinical trials. However, activity measures may be improved over 5 years while measures of damage, such as radiographic score, indicate disease progression. Two quantitative indices which are widely used in clinical trials are the (1) American College of Rheumatology (ACR) Core Data Set, which includes swollen joint count, tender joint count, physician assessment of global status, acute-phase reactant-erythrocyte sedimentation rate or C-reactive protein, functional status, pain, patient estimate of global status, a radiograph in studies over 1 year or longer, and (2) the disease activity score(DAs), which includes a swollen joint count, tender joint count, acute-phase reactant, and patient assessment of global status. Randomized controlled clinical trials provide the optimal method to evaluate new therapies, by comparing a therapy with a placebo or another therapy without selecting patients for specific therapies. However, randomized trials in chronic diseases have important limitations, including a relatively short observation period, patient selection for inclusion and exclusion criteria, inflexible dosage schedules, influence of the design on results despite a control group, emphasis on group data while ignoring individual variation in treatment responses, non-standardized interpretation of adverse effects, and others. Therefore, clinical trials in RA must be supplemented by long-term observational studies to assess results of therapy in regard to long-term outcomes such as work disability, joint replacement surgery and premature mortality. The most simple and effective method of collecting important long-term data from patients in routine clinical care is through patient self-report questionnaires.     

Cure of human carcinoma xenografts by a single dose of pretargeted yttrium-90 with negligible toxicity

A covalent conjugate (NR-LU-10/SA) was prepared between streptavidin (SA) and NR-LU-10, a mAb that binds an antigen expressed on the surface of most human carcinomas. NR-LU-10/SA was injected into nude mice bearing human tumor xenografts. Injection of biotinylated galactosyl-human serum albumin reduced the circulating levels of conjugate by 95%. Subsequent administration of (90)Y-1,4,7, 10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-biotin achieved peak uptake at the tumor within 2 hr while >80% of the radioactivity was eliminated in the urine. A single dose of 600-800 microCi of (90)Y-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-biotin produced cures in 10/10 mice with established (>200 mm(3)) s.c. human small cell lung or colon cancer xenografts and 8/10 cures in mice with human breast cancer xenografts without significant toxicity.     

Comparison of biplane and single plane left ventricular volumes in atrial septal defect

The close agreement between biplane (BP) and single-plane (SP) angiographic estimates of left ventricular (LV) volumes results from the similarity of the minor axes measured in the right anterior oblique (RAO) and left anterior oblique (LAO) views. Disease states that alter LV geometry may change the length of one minor axis more than the other, producing a discrepancy between BP and SP volumes. To examine this hyposthesis, angiographically derived volumes in 21 patients with atrial septal defects (ASD) in which the LV appears to be compressed and flattened by an enlarged right ventricle, were compared to 100 normal control patients. In the control patients, the median SP estimate of end-diastolic volume (EDV) was 7.6% larger than the BP determination, whereas in patients with ASD, the median SP EDV estimate was 16.7% larger than the BP EDV (P<0.0001). The SP end-systolic volume (ESV) underestimated the BP value by 3.4% in controls but overestimated the BP ESV in patients with ASD by 4.3% (P<0.02). The overestimate of the SP EDV and SP ESV when compared to the BP volumes may be due to changes in either the minor axes or the appearance of the longest major axis in the LAO view. The longest major axis was found in the RAO view in 99% (99/100) of normals and 95% (20/21) of ASD patients (P?NS). The median ratio of RAO to LAO end-diastolic minor axes, however, was 1.07 in the normals and 1.17 for ASD patients. The median ratio of end-systolic minor axes was 0.97 for controls and 1.04 for ASD patients. Compression of the LV in patients with ASD shortens the LAO minor axis, resulting in a significantly greater SP overestimation of LV volume than occurs in normals. The degree of SP volume overestimate was not predicted by the magnitude of the left-to-right shunt or pulmonary pressure. This source of error affects all SP methods for determining left ventricular volume, including radionuclide techniques using static images.     

SARS-CoV-2 as a superantigen in multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) is a rare but deadly new disease in children that rapidly progresses to hyperinflammation and shock, and can lead to multiple organ failure if unrecognized. It has been found to be temporally associated with the COVID-19 pandemic and is often associated with SARS-CoV-2 exposure in children. In this issue of the JCI, Porritt, Paschold, et al. identify restricted T cell receptor (TCR) β-chain variable domain (Vβ) usage in patients with severe MIS-C, indicating a potential role for SARS-CoV-2 as a superantigen. These findings suggest that a blood test that determines the presence of specific TCRβ variable gene (TRBV) segments may identify patients at risk for severe MIS-C.     

Moderate Sodium Restriction Enhances the Pressor Response to Hyperlipidemia in Obese, Hypertensive Patients

The effect of dietary sodium restriction on insulin, lipids, and blood pressure has been controversial. Evidence suggests that adverse short-term effects in response to very low-salt diets do not persist long-term with modest sodium restriction. In this study, the effects of modest dietary sodium restriction (60 and 120 mmol sodium) were measured for 3 weeks in 12 lean normotensives and 10 obese hypertensives. Blood pressure, plasma lipids, and the pressor response to an infusion of Intralipid and heparin were obtained. In contrast to previous reports concerning very low-salt diets, obese hypertensives did not manifest a pressor response or an adverse lipid effect with moderate salt restriction. Obese hypertensives were not more salt-sensitive than lean normotensives and did not manifest a different hemodynamic response to 4-hour infusion of Intralipid and heparin while on the 120-mmol/day salt diet. During the 60-mmol/day salt diet, however, plasma triglycerides increased more in obese than in lean volunteers during the Intralipid and heparin infusion (398±38 vs. 264±18 mg/dL; p<0.05), and there were greater increases in mean blood pressure (12±2 vs. 7±2 mm Hg; p<0.05) and systemic vascular resistance (111±38 vs. −25±44 dyne.sec cm—5) as well as a larger decrease in small artery compliance (−2.5±0.6 vs. −0.4±0.6 mL/mm Hg × 100; p<0.05). These data suggest that modest dietary sodium restriction in obese hypertensives does not adversely affect baseline blood pressure or lipids, but it does magnify their adverse lipid and hemodynamic response to fat loading.     

Physical inactivity in patients with rheumatoid arthritis: data from twenty-one countries in a cross-sectional, international study

OBJECTIVE: Regular physical activity is associated with decreased morbidity and mortality. Traditionally, patients with rheumatoid arthritis (RA) have been advised to limit physical exercise. We studied the prevalence of physical activity and associations with demographic and disease-related variables in patients with RA from 21 countries. METHODS: The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) is a cross-sectional study that includes a self-report questionnaire and clinical assessment of nonselected consecutive outpatients with RA who are receiving usual clinical care. Frequency of physical exercise (>or=30 minutes with at least some shortness of breath, sweating) is queried with 4 response options: >or=3 times weekly, 1-2 times weekly, 1-2 times monthly, and no exercise. RESULTS: Between January 2005 and April 2007, a total of 5,235 patients from 58 sites in 21 countries were enrolled in QUEST-RA: 79% were women, >90% were white, mean age was 57 years, and mean disease duration was 11.6 years. Only 13.8% of all patients reported physical exercise>or=3 times weekly. The majority of the patients were physically inactive with no regular weekly exercise: >80% in 7 countries, 60-80% in 12 countries, and 45% and 29% in 2 countries, respectively. Physical inactivity was associated with female sex, older age, lower education, obesity, comorbidity, low functional capacity, and higher levels of disease activity, pain, and fatigue. CONCLUSION: In many countries, a low proportion of patients with RA exercise. These data may alert rheumatologists to motivate their patients to increase physical activity levels.