Longitudinal characterisation of haematological and biochemical parameters in cancer patients prior to and during COVID-19 reveals features associated with outcome.

BACKGROUND: Cancer patients are at increased risk of death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer and its treatment affect many haematological and biochemical parameters, therefore we analysed these prior to and during coronavirus disease 2019 (COVID-19) and correlated them with outcome. PATIENTS AND METHODS: Consecutive patients with cancer testing positive for SARS-CoV-2 in centres throughout the United Kingdom were identified and entered into a database following local governance approval. Clinical and longitudinal laboratory data were extracted from patient records. Data were analysed using Mann-Whitney U test, Fisher's exact test, Wilcoxon signed rank test, logistic regression, or linear regression for outcomes. Hierarchical clustering of heatmaps was performed using Ward's method. RESULTS: In total, 302 patients were included in three cohorts: Manchester (n = 67), Liverpool (n = 62), and UK (n = 173). In the entire cohort (N = 302), median age was 69 (range 19-93 years), including 163 males and 139 females; of these, 216 were diagnosed with a solid tumour and 86 with a haematological cancer. Preinfection lymphopaenia, neutropaenia and lactate dehydrogenase (LDH) were not associated with oxygen requirement (O2) or death. Lymphocyte count (P < 0.001), platelet count (P = 0.03), LDH (P < 0.0001) and albumin (P < 0.0001) significantly changed from preinfection to during infection. High rather than low neutrophils at day 0 (P = 0.007), higher maximal neutrophils during COVID-19 (P = 0.026) and higher neutrophil-to-lymphocyte ratio (NLR; P = 0.01) were associated with death. In multivariable analysis, age (P = 0.002), haematological cancer (P = 0.034), C-reactive protein (P = 0.004), NLR (P = 0.036) and albumin (P = 0.02) at day 0 were significant predictors of death. In the Manchester/Liverpool cohort 30 patients have restarted therapy following COVID-19, with no additional complications requiring readmission. CONCLUSION: Preinfection biochemical/haematological parameters were not associated with worse outcome in cancer patients. Restarting treatment following COVID-19 was not associated with additional complications. Neutropaenia due to cancer/treatment is not associated with COVID-19 mortality. Cancer therapy, particularly in patients with solid tumours, need not be delayed or omitted due to concerns that treatment itself increases COVID-19 severity.

Aqueous humour flow in the posterior chamber of the eye and its modifications due to pupillary block and iridotomy.

The anterior chamber (AC) and posterior chamber (PC) of the eye are connected through the pupil and are filled with aqueous humour. The aqueous flows from the posterior to the AC at an approximately constant rate, and the intraocular pressure is governed by this rate and the resistance to aqueous outflow. In some patients the iris and lens come into contact, leading to pressure build-up in the PC, peripheral axial shallowing of the AC and, possibly, to angle-closure glaucoma. This can lead to blindness, which may be prevented by surgically creating an iridotomy, that is a hole through the iris to facilitate the flow from the posterior to the AC. The problem of optimal size and location of an iridotomy is still poorly understood. In this article, we study aqueous flow in the PC and investigate how it is modified in the presence of an iridotomy. Our approach is based on the lubrication theory, which allows us to solve the problem semi-analytically. We treat the iridotomy as a point sink and assume that the flux through it is proportional to the pressure. We find that the ideal size and location of an iridotomy are influenced by various geometrical and fluid mechanical factors, the most relevant of which are the size of the hole and the length and height of the iris-lens channel. For certain iridotomy diameters, we find that the jet velocity through the iridotomy might be large enough to cause possible corneal damage.

Complete Genome Sequence of the Human Herpesvirus 6A Strain AJ from Africa Resembles Strain GS from North America.

The genome sequence of human herpesvirus 6A (HHV-6A) strain AJ was determined in a comparison of target enrichment and long-range PCR using next-generation sequencing methodologies. The analyses show 85 predicted open reading frames (ORFs), conservation with sequenced HHV-6A reference strain U1102, and closest identity to the recently determined GS strain, despite different geographic origins (United States and Gambia).

Analyses of germline, chromosomally integrated human herpesvirus 6A and B genomes indicate emergent infection and new inflammatory mediators.

Human herpesvirus-6A (HHV-6A) is rarer than HHV-6B in many infant populations. However, they are similarly prevalent as germline, chromosomally integrated genomes (ciHHV-6A/B). This integrated form affects 0.1-1 % of the human population, where potentially virus gene expression could be in every cell, although virus relationships and health effects are not clear. In a Czech/German patient cohort ciHHV-6A was more common and diverse than ciHHV-6B. Quantitative PCR, nucleotide sequencing and telomeric integration site amplification characterized ciHHV-6 in 44 German myocarditis/cardiomyopathy and Czech malignancy/inflammatory disease (MI) patients plus donors. Comparisons were made to sequences from global virus reference strains, and blood DNA from childhood-infections from Zambia (HHV-6A mainly) and Japan (HHV-6B). The MI cohort were 86 % (18/21) ciHHV-6A, the cardiac cohort 65 % (13/20) ciHHV-6B, suggesting different disease links. Reactivation was supported by findings of 1) recombination between ciHHV-6A and HHV-6B genes in 20 % (4/21) of the MI cohort; 2) expression in a patient subset, of early/late transcripts from the inflammatory mediator genes chemokine receptor U51 and chemokine U83, both identical to ciHHV-6A DNA sequences; and 3) superinfection shown by deep sequencing identifying minor virus-variants only in ciHHV-6A, which expressed transcripts, indicating virus infection reactivates latent ciHHV-6A. Half the MI cohort had more than two copies per cell, median 5.2, indicative of reactivation. Remarkably, the integrated genomes encoded the secreted-active form of virus chemokines, rare in virus from childhood-infections. This shows integrated virus genomes can contribute new human genes with links to inflammatory pathology and supports ciHHV-6A reactivation as a source for emergent infection.

Verbal pragmatics following unilateral stroke: emotional content and valence.

Verbal pragmatic aspects of discourse production were examined in 16 right brain-damaged (RBD), 16 left brain-damaged (LBD), and 16 normal control right-handed adults. The facilitation effect of emotional content, valence hypothesis, and relationship between pragmatics and emotion were evaluated. Participants produced monologues while recollecting emotional and nonemotional experiences. Transcribed monologues were rated for appropriateness on 6 pragmatic features: conciseness, lexical selection, quantity, relevancy, specificity, and topic maintenance. Overall, brain-damaged groups were rated as significantly less appropriate than normals. Consistent with the facilitation effect, emotional content enhanced pragmatic performance of LBD aphasic participants yet suppressed performance of RBD participants. Contrary to the valence hypothesis, RBD participants were more impaired for positive emotions and LBD participants for negative emotions. Pragmatic appropriateness was not strongly correlated with a measure of emotional intensity.

Psychometric aspects of verbal pragmatic ratings.

This study examined the psychometric aspects of a verbal pragmatic rating scale. The scale contained six pragmatic features (i.e., Conciseness, Lexical Selection, Quantity, Relevancy, Specificity, and Topic Maintenance) based on Grice's cooperative principles. Fifteen right brain-damaged (RBD), 15 left brain-damaged (LBD), and 16 healthy normal control (NC) right-handed adult participants produced narratives while recollecting emotional and nonemotional experiences. Naive raters evaluated each pragmatic feature for appropriateness on a 5-point Likert scale. When reliability was examined, the overall internal consistency of the pragmatic scale was extremely high (alpha =.96). Factor analysis was conducted to examine the theoretical relations among the six pragmatic features. Three meaningful factors involving discourse content, conceptual unity, and parsimony were identified. Findings are discussed in light of Grice's model and the construct validity of the scale.

Hemispheric specialization for discourse reports of emotional experiences: relationships to demographic, neurological, and perceptual variables.

This study examined hemispheric specialization for discourse reports of emotional and nonemotional experience in 16 right-brain-damaged (RBD), 16 left-brain-damaged (LBD), and 16 demographically-matched normal control (NC) right-handed adults. Patient groups did not differ on etiology, months post-CVA onset, and intrahemispheric lesion location. Subjects were requested to produce monologues about positive and negative emotional and nonemotional experiences. The lexical content of written transcriptions of these monologues was later rated for "emotionality" by naive judges. Overall, RBDs described experiences with less emotional intensity than did NCs and LBDs, providing support for right hemisphere involvement in lexical emotion. Although the RBDs in the current study demonstrated similar patterns of deficits in a prior study [9] on tasks involving lexical emotional perception, there were no significant relationships between the current measures of emotional expression and the previous measures of emotional perception. Finally, the expression and the perception data were examined with respect to intrahemispheric factors. Among the brain-damaged subjects, subcortical structures were more involved in reports of emotional experience, and cortical structures were more involved in the perception of emotion.

Set-shifting and spatial orientation in patients with Parkinson's disease.

Individuals with Parkinson's disease were compared to normal control subjects on a series of widely used neuropsychological measures. The two groups were matched for gender, handedness, age, education, and occupation. The neuropsychological tests were chosen to measure two specific functions: (a) spatial orientation (i.e., measures of personal orientation, extrapersonal orientation, right/left orientation, and mental rotation), and (b) the ability to shift mental set (e.g., generating responses from alternating categories). The tests chosen to measure spatial orientation had no set-shifting component, and the tests chosen to measure set-shifting had no spatial orientation component. Multivariate statistical analyses revealed a significant difference between the subjects with Parkinson's disease and the control subjects on the measures of set-shifting ability. In contrast, no significant difference between the groups was observed on the measures of spatial orientation. These results are discussed in terms of the current speculation in the literature regarding the relationship between set-shifting deficits and a disruption of dopaminergic fibers to the prefrontal cortex in Parkinson's disease.

Right hemisphere specialization for the identification of emotional words and sentences: evidence from stroke patients.

This study examines the contribution of the lexical/verbal channel to emotional processing in 16 right brain-damaged (RBD), 16 left brain-damaged (LBD) and 16 normal control (NC) right-handed adults. Emotional lexical perception tasks were developed; analogous nonemotional tasks were created to control for cognitive and linguistic factors. The three subject groups were matched for gender, age and education. The brain-damaged groups were similar with respect to cerebrovascular etiology, months post-onset, sensory-motor status and lesion location. Parallel emotional and nonemotional tasks included word identification, sentence identification and word discrimination. For both word tasks, RBDs were significantly more impaired than LBDs and NCs in the emotional condition. For all three tasks, RBDs showed a significantly greater performance discrepancy between emotional and nonemotional conditions than did LBDs or NCs. Results were not affected by the valence (i.e. positive/negative) of the stimuli. These findings suggest a dominant role for the right hemisphere in the perception of lexically-based emotional stimuli.

Neuropsychological aspects of Parkinson's disease.

The neuropsychological effects of Parkinson's disease have gained wide recognition in recent literature. Effects have been documented in almost all areas of cognitive functioning, including general intellectual functioning, visual-spatial functioning, executive functions, attention and memory functions, language functions, and affective processes. Visual-spatial functions, memory functions, and executive functions have received particular interest. This review of the literature is an attempt to tie together the large number of studies in these cognitive areas and to present a suggestion for a comprehensive neuropsychological battery tailored to the patient with Parkinson's disease. Throughout the review, factors relevant to Parkinson's disease, e.g., dementia, motor symptoms, and hemiparkinsonism, are considered.

Effect of inversion on memory for faces in Parkinson's disease and right-hemisphere stroke patients.

Upright and upside-down photographs of faces, schematic drawings of faces, and photographs of houses were presented to patients with Parkinson's disease (PD), patients with right hemisphere stroke (RH), and age-matched normal control subjects (NC) in a forced-choice recognition paradigm. These slides were presented in four orientation conditions: upright at original presentation and at test, upside-down at both, upright initially and upside-down at test, and vice versa. NC subjects recognized faces most accurately when presented in the same orientation both times. This suggests that the information is resistant to mental rotation. Patients with PD recognized faces most accurately when they were presented upright both times, suggesting difficulty with any unusual orientation, consistent with an inability to shift mental set. RH patients, unlike the other groups, did not recognize faces presented upright both times more accurately than those in any other condition. This supports previous studies suggesting a right hemisphere specialization for recognition of upright faces.

Evaluating evidence for automaticity in frequency of occurrence judgments: a bias for bias?

Frequency of occurrence judgments were evaluated in young adults recovering from closed-head injuries, normal elderly, and young adult controls. Impaired performance was observed in both head-injured and elderly subjects, a result contrary to Hasher and Zacks' 1979 hypothesis that this information accumulates in memory via automatic processes which are unaffected by age, but supporting their conjecture that damage to the central nervous system would be sufficient to interfere with this function. The head-injured subject's performance on the frequency judgment task was correlated with effortful memory capacity as measured by several widely used memory tests. Whether the obtained group differences reflect differences in memory capacity or response criteria effects is discussed, and several methods of analyzing the data are compared.

Cerebral blood flow in severity-matched Alzheimer and multi-infarct patients.

Cerebral blood flow was studied in patients meeting research criteria for either Alzheimer's disease or multi-infarct dementia, matched for age and severity of dementia. In both groups, mean flow was less than in age-matched normal controls, but the Alzheimer patients also had significantly lower mean flow than the multi-infarct group. This result helps resolve discrepancies found in studies with inadequate control for severity. Either global flow or regional left parietal flow could be used to discriminate between these dementia categories with 87% accuracy.

Hand preference and performance effects on line bisection.

Right- and left-handed subjects performed a visual line bisection task with each hand. When bisecting horizontal lines, both groups bisected left of true center regardless of hand used. Regardless of hand preference, bisections were significantly left of center only when subjects performed with their left hand. Left-handed subjects using their left hand deviated significantly further left than right-handed subjects using their left hand. Regardless of hand used, right-handers bisected vertical lines significantly above veridical center. Left-handed subjects were not significantly above center with either hand. The results require both hemispheric advantage and lateralized activation effects for a complete explanation.

Underdiagnosis of cognitive impairment in a rehabilitation setting.

Of 100 patients consecutively admitted to a rehabilitation hospital, 25 were cognitively impaired. On two brief tests of intellectual function, they scored below the criteria selected by the originators of those tests for clinically significant mental impairment. Nineteen of the 25 had vascular disease of the heart, brain, or peripheral vessels; two had cardiac valvular disease; three had head trauma; and one was mentally retarded. Mental impairment appears to be relatively common among the hospitalized elderly who do not carry the primary diagnosis of "dementia" or "organic brain syndrome." It appears to be particularly common among those with cardiovascular disease, even without frank stroke. Brief mental status examinations should be part of the routine evaluation of such patients.

The effect of semantic relations on the memory deficit associated with Parkinson's disease.

Analysis of a series of verbal memory experiments reveals a systematic performance deficit in subjects with Parkinson's disease, relative to matched normal and right-hemisphere stroke controls, in both recall and recognition tasks. Parkinson patients benefit less from semantic recall cues; they find semantically mediated synonym detections particularly difficult; and they show reduced benefits from the introduction of semantically novel material in a recall task. Their recall is as well organized semantically as that of normal controls, but reduced in amount. Recognition deficits arise principally from increases in false positive responses.

Lecithin treatment of cognitively impaired Parkinson's patients.

To test the effects of lecithin on cognitive deficits associated with Parkinson's disease, sixteen elderly and mentally-impaired outpatients with Parkinson's disease participated in a 9-week double-blind placebo-controlled study. Each patient took a daily dose of approximately 32 g of a commercial lecithin preparation containing 25% phosphatidylcholine, or an equivalent amount of powdered skim milk placebo. Marked clinical improvement was not observed, but some indications of a positive treatment effect were obtained on memory, cognition, and motility tests.