Collecting and evaluating convalescent plasma for COVID-19 treatment: why and how?

Plasma provided by COVID-19 convalescent patients may provide therapeutic relief as the number of COVID-19 cases escalates steeply worldwide. Prior findings in various viral respiratory diseases including SARS-CoV-related pneumonia suggest that convalescent plasma can reduce mortality, although formal proof of efficacy is still lacking. By reducing viral spread early on, such an approach may possibly downplay subsequent immunopathology. Identifying, collecting, qualifying and preparing plasma from convalescent patients with adequate SARS-CoV-2-neutralizing Ab titres in an acute crisis setting may be challenging, although well within the remit of most blood establishments. Careful clinical evaluation should allow to quickly establish whether such passive immunotherapy, administered at early phases of the disease in patients at high risk of deleterious evolution, may reduce the frequency of patient deterioration, and thereby COVID-19 mortality.     

Episodic memory bias and the symptoms of schizophrenia.

Much of the research on episodic memory in schizophrenia spectrum disorders has focused on memory deficits and how they relate to clinical measures such as outcome. Memory bias refers to the modulatory influence that state or trait psychopathology may exert on memory performance for specific categories of stimuli, often emotional in nature. For example, subjects suffering from depression frequently have better memory for negative stimuli than for neutral or positive ones. This dimension of memory function has received only scant attention in schizophrenia research but could provide fresh new insights into the relation between symptoms and neurocognition. This paper reviews the studies that have explored memory biases in individuals with schizophrenia. With respect to positive symptoms, we examine studies that have explored the link between persecutory delusions and memory bias for threatening information and between psychosis and a memory bias toward external source memory. Although relatively few studies have examined negative symptoms, we also review preliminary evidence indicating that flat affect and anhedonia may lead to some specific emotional memory biases. Finally, we present recent findings from our group delineating the relation between emotional valence for faces and memory bias toward novelty and familiarity, both in schizophrenia patients and in healthy control subjects. A better understanding of the biasing effects of psychopathology on memory in schizophrenia (but also on other cognitive functions, such as attention, attribution, and so forth) may provide a stronger association between positive and negative symptoms and memory function. Memory measures sensitive to such biases may turn out to be stronger predictors of clinical and functional outcome.     

Generalization of Frequency Discrimination Learning Across Frequencies and Ears: Implications for Underlying Neural Mechanisms in Humans

Frequency discrimination thresholds (FDTs) at 750, 1500, 3000, and 6000 Hz were measured in 32 normal-hearing listeners before and after each listener practiced the task for 12 h at one of the above frequencies using a single ear. Marked improvements in thresholds taking place over several hours were observed during the frequency- and ear-specific training period. Comparisons between pre- and posttraining thresholds showed large improvements at the trained frequency, but also at other frequencies. The improvements were initially slightly—but significantly—larger at the trained frequency than at untrained frequencies. However, this trained-frequency advantage disappeared rapidly during the course of the two-hour multifrequency posttraining session, suggesting rapid relearning or learning generalization across frequencies. In contrast, no significant ear specificity was found, not even at early stages of the posttraining session. These findings add to earlier results suggesting that, in humans, frequency discrimination learning is only weakly frequency-specific, and they reveal that a complete generalization across frequencies can occur rapidly with little retraining at the initially untrained frequencies. Implications regarding underlying mechanisms are discussed.     

Effects of Intermittent Femoral Nerve Injections of Bupivacaine, Levobupivacaine, and Ropivacaine on Mitochondrial Energy Metabolism and Intracellular Calcium Homeostasis in Rat Psoas Muscle

Background: Long-acting local anesthetics cause muscle damage. Moreover, long-acting local anesthetics act as uncoupler of oxidative phosphorylation in isolated mitochondria and enhance sarcoplasmic reticulum Ca2+ release. The aim of the study was to evaluate effects of perineural injections of local anesthetics on mitochondrial energetic metabolism and intracellular calcium homeostasis in vivo.

Methods: Femoral nerve block catheters were inserted in adult male Wistar rats. Rats were randomized and received seven injections (1 ml/kg) of bupivacaine, levobupivacaine, ropivacaine, or isotonic saline at 8-h intervals. Rats were killed 8 h after the last injection. Psoas muscle was quickly dissected from next to the femoral nerve. Local anesthetic concentrations in muscle were determined. Oxidative capacity was measured in saponin-skinned fibers. Oxygen consumption rates were measured, and mitochondrial adenosine triphosphate synthesis rate was determined. Enzymatic activities of mitochondrial respiratory chain complexes were evaluated. Local calcium release events (calcium sparks) were analyzed as well as sarcoplasmic reticulum calcium content in saponin-skinned fibers.

Results: Eight hours after the last injection, psoas muscle concentration of local anesthetics was less than 0.3 [mu]g/g tissue. Adenosine triphosphate synthesis and adenosine triphosphate-to-oxygen ratio were significantly decreased in the muscle of rats treated with local anesthetics. A global decrease (around 50%) in all of the enzyme activities of the respiratory chain was observed. Levobupivacaine increased the amplitude and frequency of the calcium sparks, whereas lower sarcoplasmic reticulum calcium content was shown.     

Role of blast cell immunophenotyping for the diagnosis and prognosis of acute myeloid leukemia.

Bone marrow blast cell antigen expression from 86 patients with de novo acute myeloid leukemias (AML) was studied and correlated with FAB classification and clinical outcome. Among a panel of 14 monoclonal antibodies routinely used for the diagnosis of acute leukemias we studied the expression of six antibodies (CD13, CD15, VIM2, CD33, CD14, CD34) of the granulomonocytic lineage and found that some of them were useful for diagnosis and/or prognosis. For FAB subclassification of AML, the CD13 or VIM2 antigen expression was of no benefit. Monocytic leukemias (M4 + M5PD + M5WD) more frequently expressed CD34 antigen (28/31) than granulocytic (M1 + M2 + M3) subtypes (33/53) (P < 0.01). Finally, the most striking differences were found with CD14 antigen expression: CD14 antigen was more frequently expressed in M4 + M5 leukemias (21/31) than in M1 + M2 + M3 subtypes (12/33) (P < 0.01). The mean percentage of CD14 positive blast cells was accordingly higher in monocytic leukemias than in granulocytic leukemias and the difference was highly significant (P < 0.0001). The CD15 antigen was more frequently expressed in differentiated leukemias (M2 + M3 + M4 + M5WD) (35/44) than in poorly differentiated forms (M1 + M5PD) (17/37) (P < 0.001). The statistical difference was higher when the mean percentage of CD15 positive blast cells were compared (P < 0.0003). Moreover these latter percentages were different in M1 and M2 subtypes (P < 0.003). The blast cell expression of CD13, CD14, CD15 or CD33 was not predictive of the length of CR or survival. Moreover, our results support previously published findings suggesting a longer overall survival duration for patients whose leukemic cells do not express the CD34 antigen (P < 0.01). We also confirm that patients with the more differentiated subtypes of AML (CD13-, CD34+) tend to survive longer than patients with the less differentiated subtypes of AML (CD13-, CD34+) (P < 0.001).     

Diversity of tick species biting humans in an emerging area for Lyme disease.

BACKGROUND. Although most tick bites in humans in areas of the northeastern United States in which Lyme disease is highly endemic are due to Ixodes dammini, no study documents the frequency of I. dammini bites in low-prevalence or emerging areas for Lyme disease. Data on the proportion of tick bites in humans that are due to I. dammini in a region may have implications for public health policy and clinical management. METHODS. A statewide survey of the tick species that parasitized humans in Maine was conducted during 1989 and 1990. Tick submissions from throughout the state were elicited through media announcements. All ticks that had been removed from humans were identified, and data were collected that included bite seasonality and geography and demographics of tick bite victims. RESULTS. Of 709 ticks submitted, only 17% were I. dammini. Ixodes cookei, a vector for Powassan encephalitis, accounted for 34% of bites, and Dermacentor variabilis accounted for 45%. Other tick species were occasionally implicated. CONCLUSIONS. The likelihood that a tick bite was due to I. dammini was lower in Maine than in areas in the northeastern United States in which Lyme disease is highly endemic. Other tick vectors, associated with diseases other than Lyme disease, were more frequently implicated. Regional tick bite surveys may prove useful in assessing the risk of Lyme disease following a tick bite.     

Preliminary experience with inhaled milrinone in cardiac surgery

Background: Inhaled administration of milrinone reduces pulmonary artery pressure. Pulmonary hypertension (PH) and right heart failure are associated with difficult separation from cardiopulmonary bypass (CPB). Therefore, inhaled milrinone could facilitate separation from CPB. Objective: To determine the impact and timing of administration of inhaled milrinone. Methods: A retrospective analysis of our experience on high-risk patients receiving inhaled milrinone was conducted to evaluate the postoperative course after administration of the drug. Results: Seventy-three patients received inhaled milrinone from June 2002 to February 2005. Mean age was 64 ± 13 years, with a mean preoperative Parsonnet score of 27 ± 14. Inhaled milrinone (5 mg) was administered before (n = 30) or after (n = 40) CPB, three patients had off-pump procedures and were excluded. CPB time was 145 ± 78 min with cross-clamping times of 91 ± 56 min without any significant difference between groups. Fifty-four patients (74%) had difficult separation from CPB, 14 patients (19%) required an intra-aortic balloon pump and 10 patients (14%) needed emergency reinitiation of CPB for hemodynamic instability. Ten patients died in the perioperative period (13.7%). Patients receiving inhaled milrinone prior to CPB initiation had a lowering pulmonary artery pressure after CPB (p < .01) and had less emergency reinitiation of CPB after weaning (3% vs 23%, p = .02) as compared to those with administration after CPB. No detectable side effects were directly linked to the administration of the drug. Conclusion: In this high-risk cohort, use of inhaled milrinone was well tolerated. Administration before initiation of CPB could help weaning from CPB.