Measurement of brain lactate during visual stimulation using a long TE semi‐LASER sequence at 7 T

Estimation of metabolic changes during neuronal activation represents a challenge for in vivo MRS, especially for metabolites with low concentration and signal overlap, such as lactate. In this work, we aimed to evaluate the feasibility of detecting lactate during brain activation using a long (144 ms) semi‐LASER sequence at 7 T. spectra were acquired on healthy volunteers ( ) during a paradigm with 15 min of visual stimulation. Outer‐volume signals were further attenuated by the use of saturation slabs, and macromolecular signals in the vicinity of the inverted lactate peak were individually fitted with simulated Lorentzian peaks. All spectra were free of artefacts and highly reproducible across subjects. Lactate was accurately quantified with an average Cramér‐Rao lower bound of 8%. Statistically significant ( , one‐tailed ‐test) increases in lactate ( 10%) and glutamate ( 3%) levels during stimulation were detected in the visual cortex. Lactate and glutamate changes were consistent with previous measurements. We demonstrated that quantification of a clear and non‐contaminated lactate peak obtained with a long TE sequence has the potential of improving the accuracy of functional MRS studies targeting non‐oxidative reaction pathways.     

Comparison of inhaled nitric oxide with aerosolized prostacyclin or analogues for the postoperative management of pulmonary hypertension: a systematic review and meta-analysis

Abstract

Background: This study aims to compare the effectiveness of inhaled prostacyclin or its analoguesversus nitric oxide (NO) in treating pulmonary hypertension (PH) after cardiac or pulmonary surgery remains unclear.

Methods: PubMed, Cochrane, and Embase databases were searched for literature published prior to December 2019 using the following keywords: inhaled, nitric oxide, prostacyclin, iloprost, treprostinil, epoprostenol, Tyvaso, flolan, and pulmonary hypertension. Randomized controlled trials and multiple-armed prospective studies that evaluated inhaled NO versus prostacyclin (or analogues) in patients for perioperative and/or postoperative PH after either cardiac or pulmonary surgery were included. Retrospective studies, reviews, letters, comments, editorials, and case reports were excluded.

Results: Seven studies with a total of 195 patients were included. No difference in the improvement of mean pulmonary arterial pressure (pooled difference in mean change= ?0.10, 95% CI: ?3.98 to 3.78, p?=?.959) or pulmonary vascular resistance (pooled standardized difference in mean change= ?0.27, 95% CI: ?0.60 to 0.05, p?=?.099) were found between the two treatments. Similarly, no difference was found in other outcomes between the two treatments or subgroup analysis.

Conclusions: Inhaled prostacyclin (or analogues) was comparable to inhaled NO in treating PH after cardiac or pulmonary surgery.

• Key messages

• This study compared the efficacy of inhaled prostacyclin or its analogues versus inhaled NO to treat PH after surgery. The two types of agent exhibited similar efficacy in managing MPAP, PVR, heart rate, and cardiac output was observed.

• Inhaled prostacyclin may serve as an alternative treatment option for PH after cardiac or pulmonary surgery.

     

Association between cranial asymmetry severity and chronic subdural hematoma laterality

Objectives:To analyze the association between cranial asymmetry severity and chronic subdural hematoma (CSDH) laterality.Methods:We retrospectively assessed 120 patients with surgically treated unilateral CSDH from January 2009 to December 2018. Preoperative computed tomography images were used to determine occipital vault angles, bilateral cranium areas, and cranial index of symmetry (CIS) ratios.Results:The male sex (70%) was the predominant factor promoting CSDH pathogenesis. In the overall study population (mean age, 71.3 years; left-sided CSDH, 58/120 [48%] patients; right-sided CSDH due to right-sided flat cranium, 38 patients; left-sided CSDH due to right-sided flat cranium, 37 patients). Flat cranial asymmetry was nonsignificantly associated with CSDH laterality (p- value=.689). However, most CSDH patients (86.7% of 120 patients) presented dominant-sided nonoverlapping areas on the left side. Thirteen (81.3%) patients presenting right-dominant nonoverlapping areas had right-sided CSDH, and 55 (52.9%) patients had left-dominant nonoverlapping area had left-sided CSDH (p- value=0.01). The CIS ratio was significantly higher in patients with right-dominant nonoverlapping areas than in those with left-dominant nonoverlapping areas (97.2% vs 95.9%, p- value<0.0001).Conclusion:Left-sided hematoma predominance is not associated with a flat cranium and laterality of unilateral CSDH. Moreover, more asymmetric crania with lower CIS ratios may predict left-sided CSDHs, whereas the right-sided CSDHs may be more common in symmetric crania with higher CIS ratios. The CSDH laterality is potentially attributable to cranial asymmetry severity.

Chronic subdural hematoma (CSDH), a common neurosurgical entity, is considered a delayed manifestation of head trauma, occurring mostly in older men.1 Although CSDHs can occur in unilateral or bilateral intracranial spaces, left-sided predominance has been previously reported.2,3 Few studies have reported that cranial morphology and gravity contribute to the laterality of CSDH.4–6 Cranial asymmetry is more common among crania flattened toward the right side, influencing the left-sided predominance of CSDH.6 The cranial index of symmetry (CIS) with a semiautomated method has been introduced to objectively determine the severity of cranial deformations including plagiocephaly.7 A preliminary study reported that the objective nonradiographic method potentially serves as an unbiased measurement of cranial asymmetry.7 The flat side has been simply defined by a smaller angle through a simple method considering angles among 3 lines.4–6 However, the angles may be manually affected by the points of the intersection of the manually selected lines, thus obstructing cranial asymmetry assessment. Therefore, here, we aimed to clarify the association between the severity of cranial asymmetry and the laterality of CSDH by using an objective semiautomated method.     

Lenalidomide plus dexamethasone for proliferative glomerulonephritis with monoclonal immunoglobulin deposits

Objective To evaluate the efficacy and safety of lenalidomide plus dexamethasone (LD) in patients with proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID). Methods The clinicopathological data of PGNMID patients who were treated with LD protocol from January 2010 to October 2019 were retrospectively analyzed. Results All of 6 patients received LD treatment for≥3 months after renal biopsy in Jinling Hospital. During the follow-up period of 6 to 19 months, 3 patients achieved renal remission, and the renal remission rate was 50%(3/6). Light microscopy showed membranoproliferative glomerulonephritis and immunofluorescence showed single kappa type IgG3 was deposited in the mesangial region and the vascular loop. Before taking LD scheme, the median urinary protein were 7.76(1.27, 14.57) g/24 h, the median serum creatinine was 118.5(70.7, 289.1) μmol/L, and the median albumin was 34.5(22.4, 37.5) g/L. The concentration of serum free kappa and lambda light chain was increased in 5 patients, but the serum free light chain ratio was normal. Hypocomplementemia was detected in two cases. Six patients underwent bone marrow flow cytometry, and 2 patients had elevated monoclonal plasma cells, accounting for 0.7% and 0.5%, respectively. Immunofixation electrophoresis suggested that 1 patient had positive serum M protein for kappa type IgG3. At the last follow-up, median urine protein was 3.33(0.33, 11.23) g/24 h, median serum creatinine was 108.7(80.4, 160.9) μmol/L, and median albumin was 35.9(24.5, 45.6) g/L. The concentration of serum free light chain in 4 patients from 5 patients with elevated serum free light chain was lower than that before taking the drug. Decreased level of serum complement in two cases returned to normal after treatment. The M spike did not turn negative during the follow-up in one patient. Adverse events included anemia, neutropenia, limb numbness and upper respiratory tract infection. Conclusion This study reports for the first time that LD protocol may be effective in treating PGNMID, but more attention should be paid to the hematological adverse events of lenalidomide.     

The Protective Effects of Up-Regulating Prostacyclin Biosynthesis on Neuron Survival in Hippocampus

Cellular arachidonic acid (AA), an unsaturated fatty acid found ubiquitously in plasma membranes, is metabolized to different prostanoids, such as prostacyclin (PGI₂) and prostaglandin E₂ (PGE₂), by the three-step reactions coupling the upstream cyclooxygenase (COX) isoforms (COX-1 and COX-2) with the corresponding individual downstream synthases. While the vascular actions of these prostanoids are well-characterized, their specific roles in the hippocampus, a major brain area for memory, are poorly understood. The major obstacle for its understanding in the brain was to mimic the biosynthesis of each prostanoid. To solve the problem, we utilized Single-Chain Hybrid Enzyme Complexes (SCHECs), which could successfully control cellular AA metabolites to the desired PGI₂ or PGE₂. Our in vitro studies suggested that neurons with higher PGI₂ content and lower PGE₂ content exhibited survival protection and resistance to Amyloid-β-induced neurotoxicity. Further extending to an in vivo model, the hybrid of PGI₂-producing transgenic mice and Alzheimer’s disease (AD) mice showed restored long-term memory. These findings suggested that the vascular prostanoids, PGI₂ and PGE₂, exerted significant regulatory influences on neuronal protection (by PGI₂), or damage (by PGE₂) in the hippocampus, and raised a concern that the wide uses of aspirin in cardiovascular diseases may exert negative impacts on neurodegenerative protection.

Our study intended to understand the crosstalk of prostanoids in the hippocampus, a major brain area impacted in AD, by using hybrid enzymes to redirect the synthesis of prostanoids to PGE₂ and PGI₂, respectively. Our data indicated that during inflammation, the vascular mediators, PGI₂ and PGE₂, exerted significant regulatory influences on neuronal protection (by PGI₂), or damage (by PGE₂) in the hippocampus. These findings also raised a concern that the widely uses of non-steroidal anti-inflammatory drugs in cardiovascular diseases may exert negative impacts on neurodegenerative protection.

     

Predictors for Survival and Distribution of 21-Gene Recurrence Score in Patients With Pure Mucinous Breast Cancer: A SEER Population-Based Retrospective Analysis

Background

Pure mucinous breast cancer (PMBC) is a rare pathologic type of breast cancer, the prognostic factors of which have not been clearly defined. This study aimed to analyze the prognostic markers and distribution of 21-gene recurrence score (RS) in patients with PMBC.

A Canadian Prospective Study of Linkage of Randomized Clinical Trial to Cancer and Mortality Registry Data

In a prospective study, we sought to determine acceptability of linkage of administrative and clinical trial data among Canadian patients and Research Ethics Boards (REBs). The goal is to develop a more harmonized approach to data, with potential to improve clinical trial conduct through enhanced data quality collected at reduced cost and inconvenience for patients. On completion of the original LY.12 randomized clinical trial in lymphoma ({"type":"clinical-trial","attrs":{"text":"NCT00078949","term_id":"NCT00078949"}}NCT00078949), participants were invited to enrol in the Long-term Innovative Follow-up Extension (LIFE) component. Those consenting to do so provided comprehensive identifying information to facilitate linkage with their administrative data. We prospectively designed a global assessment of this innovative approach to clinical trial follow-up including rates of REB approval and patient consent. The pre-specified benchmark for patient acceptability was 80%. Of 16 REBs who reviewed the research protocol, 14 (89%) provided approval; two in Quebec declined due to small patient numbers. Of 140 patients invited to participate, 115 (82%, 95% CI 76 to 88%) from across 9 Canadian provinces provided consent and their full name, date of birth, health insurance number and postal code to facilitate linkage with their administrative data for long-term follow-up. Linkage of clinical trial and administrative data is feasible and acceptable. Further collaborative work including many stakeholders is required to develop an optimized secure approach to research. A more coordinated national approach to health data could facilitate more rapid testing and identification of new effective treatments across multiple jurisdictions and diseases from diabetes to COVID-19.     

Association of Multiple Plasma Biomarker Concentrations with Progression of Prevalent Diabetic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study

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