Neurologic manifestations of COVID-19 in critically ill patients: results of the prospective multicenter registry PANDEMIC.

BACKGROUND: Neurologic manifestations are increasingly reported in patients with coronavirus disease 2019 (COVID-19). Yet, data on prevalence, predictors and relevance for outcome of neurological manifestations in patients requiring intensive care are scarce. We aimed to characterize prevalence, risk factors and impact on outcome of neurologic manifestations in critically ill COVID-19 patients. METHODS: In the prospective, multicenter, observational registry study PANDEMIC (Pooled Analysis of Neurologic DisordErs Manifesting in Intensive care of COVID-19), we enrolled COVID-19 patients with neurologic manifestations admitted to 19 German intensive care units (ICU) between April 2020 and September 2021. We performed descriptive and explorative statistical analyses. Multivariable models were used to investigate factors associated with disorder categories and their underlying diagnoses as well as to identify predictors of outcome. RESULTS: Of the 392 patients included in the analysis, 70.7% (277/392) were male and the mean age was 65.3 (SD ± 3.1) years. During the study period, a total of 2681 patients with COVID-19 were treated at the ICUs of 15 participating centers. New neurologic disorders were identified in 350 patients, reported by these centers, suggesting a prevalence of COVID-19-associated neurologic disorders of 12.7% among COVID-19 ICU patients. Encephalopathy (46.2%; 181/392), cerebrovascular (41.0%; 161/392) and neuromuscular disorders (20.4%; 80/392) were the most frequent categories identified. Out of 35 cerebrospinal fluid analyses with reverse transcriptase PCR for SARS-COV-2, only 3 were positive. In-hospital mortality was 36.0% (140/389), and functional outcome (mRS 3 to 5) of surviving patients was poor at hospital discharge in 70.9% (161/227). Intracerebral hemorrhage (OR 6.2, 95% CI 2.5-14.9, p < 0.001) and acute ischemic stroke (OR 3.9, 95% CI 1.9-8.2, p < 0.001) were the strongest predictors of poor outcome among the included patients. CONCLUSIONS: Based on this well-characterized COVID-19 ICU cohort, that comprised 12.7% of all severe ill COVID-19 patients, neurologic manifestations increase mortality and morbidity. Since no reliable evidence of direct viral affection of the nervous system by COVID-19 could be found, these neurologic manifestations may for a great part be indirect para- or postinfectious sequelae of the infection or severe critical illness. Neurologic ICU complications should be actively searched for and treated.

Low health literacy is associated with higher risk of type 2 diabetes: a cross-sectional study in Germany.

BACKGROUND: Low health literacy is believed to be associated with behaviours that increase the risk of type 2 diabetes. But there is limited knowledge on the relation between health literacy (HL) and diabetes risk, and whether improving HL could be a potential prevention strategy. Therefore, the main purpose of this study was to examine the link between HL and diabetes risk among non-diabetic adults. METHODS: We used data from the Hamburg Diabetes Prevention Survey, a population-based cross-sectional study in Germany. One thousand, two hundred and fifty-five non-diabetic subjects aged 18-60 years were eligible. The German Diabetes Risk Score (GDRS, ranging 0 to 123 points) was used to determine the individual risk of type 2 diabetes. The short version of the European Health Literacy Questionnaire (HLS-EU-Q16, ranging 0 to 16 points) was applied to assess the individual self-reported HL. Subjects were asked to self-estimate their diabetes risk, which was then compared with the calculated GDRS. Descriptive statistics were calculated to investigate group differences in the GDRS and self-estimated diabetes risk. Linear as well as logistic regression models were performed to analyse potential influencing variables of the GDRS as well as incorrect self-estimated diabetes risk. In three nested statistical models for each outcome, these analyses were adjusted for age, gender, educational level and the presence of chronic conditions. RESULTS: According to the criteria of the GDRS, 996 (79.4%) subjects showed "low risk", 176 (14.0%) "still low risk", 53 (4.2%) "elevated risk", and 30 (2.4%) "high to very high risk" to develop type 2 diabetes within the next 5 years. In the statistical models including all control variables, subjects with "inadequate HL" scored 2.38 points higher on the GDRS (95% CI 0.378 to 4.336; P = 0.020) and had a 2.04 greater chance to estimate their diabetes risk incorrectly (OR 2.04; 95% CI 1.33 to 3.14; P = 0.001) compared to those with "sufficient HL". CONCLUSION: The risk of type 2 diabetes is increased in people with inadequate self-reported HL. People with high diabetes risk and inadequate HL might be provided with educational programs to improve diabetes knowledge and reduce behavioural risk factors.

The Link Between Health Literacy and Three Conditions of Metabolic Syndrome: Obesity, Diabetes and Hypertension.

Purpose: Health literacy (HL) intervention could be a potential prevention strategy to reduce the risk of metabolic syndrome (MS), but the association between low HL and MS is controversial. Therefore, the aim of this study was to investigate whether low HL is associated with obesity, diabetes, and hypertension, considering them as one cluster. Methods: We used data from the Hamburg Diabetes Prevention Survey, a population-based cross-sectional study in Germany. The 1349 eligible subjects were 18-60 years old. The European Health Literacy Questionnaire (HLS-EU-Q16) was used to assess HL. Depending on the reported number of metabolic syndrome conditions (CMS), four groups were categorized as follows: "0", any "1", any "2" and "3" CMS. Ordered logistic regression was used to analyze the relationship between HL level (independent variable) and the reported number of CMS (dependent variable) adjusted for age, gender and education. Results: 63.9% of subjects (n=862) reported having "0", 25.7% (n=346) only "1", 8.2% (n=111) only "2" and 2.2% (n=30) "3" of the three CMS. In the group with sufficient HL, rates of "1," "2," or "3" CMS were lower than in the group with problematic or inadequate HL. Subjects with inadequate HL showed a 1.62-fold higher risk of having a higher number of CMS than subjects with sufficient HL (OR 1.62; 95% CI 1.13 to 2.31). The risk increased with each life year (OR 1.05; 95% CI 1.04 to 1.06), and was higher in persons with low education (OR 2.89; 95% CI 2.08 to 4.01) than in highly educated persons. Women showed lower risk (OR 0.73; 95% CI 0.58 to 0.91) than men. Conclusion: Lower HL was associated with a higher number of MS conditions. Our findings suggest that HL intervention on health-promoting behaviors could help reduce MS risk in people with limited HL.

Reactive increase of cerebrospinal fluid white blood cell count after lumbar puncture: Fact or fiction?

Lumbar puncture (LP) is commonly used in the diagnostic workup of neurological patients, often to exclude inflammatory diseases of the central nervous system. In clinical practice, an increase of white blood cell count (WBC) in the cerebrospinal fluid (CSF) after a LP is often assumed as reactive to the first puncture. Scientific evidence of this hypothesis, however, is lacking. Retrospective review of laboratory parameters was done by analyzing CSF of patients who had at least two LPs between 2012 and 2016 in a single center. Inclusion criteria were a normal CSF WBC in the first LP as well as absence of any underlying disease typically associated with increased CSF WBC. A total of 176 patients (age 57.0 ± 17.6) with 260 serial LPs were included. No significant effect on the CSF WBC (1.2 ± 1.1 vs 1.4 ± 1.4/µl, p = .17), lactat and protein level between consecutive punctures was found after a second LP. In the subgroup of 104 patients who had two LPs within ten days, only one (0.96%) showed a mild abnormal CSF WBC (9 leukocytes/µl) in the second LP. A raise of CSF WBC after LP is rare and not commonly found; therefore, it should lead to careful exclusion of other, especially inflammatory diseases. The needle size is important to minimize the trauma during LP and seems to have an influence on the rate of reactive increase of CSF WBC after LP.

Scintigraphic evaluation of cheek teeth in clinically sound horses.

Dental disorders are one of the top-ranking clinical domains in equine practice. Scintigraphy has emerged as a useful diagnostic imaging modality for equine dental diseases. There is a paucity of the normal scintigraphic uptake and its correlation with age. This prospective, cross-sectional, descriptive and pilot-designed study aimed to describe the radioisotope uptake (RU) patterns of the reserved crown and periodontal bone of the maxillary and mandibular cheek teeth (CT) in clinically sound horses and to evaluate the age effect on RU. For this purpose, 60 horses that underwent a bone scintigraphy for reason unrelated to head were included and divided equally into four age groups. Regions of interests (ROIs) were positioned around alveolar and periodontal bone of each maxillary and mandibular CT including their reserve crown, and a reference ROI positioned at the mandibular ramus. The count per pixel of each ROI was measured using a dedicated software and the RU ratio relative to the reference region was calculated. The results showed that the maxillary and mandibular CT had a standard RU pattern, where it increased from rostral to caudal, and peaked in the middle of dental arcades and decreased slightly towards the last CT. The maxillary CT had a higher RU compared with the mandibular CT, and there was no significant difference in the maxillary and mandibular CT uptake between age groups. This information may aid veterinarians evaluating potentially abnormal dental scintigraphy.

Biomodulatory Treatment With Azacitidine, All-trans Retinoic Acid and Pioglitazone Induces Differentiation of Primary AML Blasts Into Neutrophil Like Cells Capable of ROS Production and Phagocytosis.

Effective and tolerable salvage therapies for elderly patients with chemorefractory acute myeloid leukemia (AML) are limited and usually do not change the poor clinical outcome. We recently described in several chemorefractory elderly AML patients that a novel biomodulatory treatment regimen consisting of low-dose azacitidine (AZA) in combination with PPARγ agonist pioglitazone (PGZ) and all-trans retinoic acid (ATRA) induced complete remission of leukemia and also triggered myeloid differentiation with rapid increase of peripheral blood neutrophils. Herein, we further investigated our observations and comprehensively analyzed cell differentiation in primary AML blasts after treatment with ATRA, AZA, and PGZ ex vivo. The drug combination was found to significantly inhibit cell growth as well as to induce cell differentiation in about half of primary AML blasts samples independent of leukemia subtype. Notably and in comparison to ATRA/AZA/PGZ triple-treatment, effects on cell growth and myeloid differentiation with ATRA monotherapy was much less efficient. Morphological signs of myeloid cell differentiation were further confirmed on a functional basis by demonstrating increased production of reactive oxygen species as well as enhanced phagocytic activity in AML blasts treated with ATRA/AZA/PGZ. In conclusion, we show that biomodulatory treatment with ATRA/AZA/PGZ can induce phenotypical and functional differentiation of primary AML blasts into neutrophil like cells, which aside from its antileukemic activity may lower neutropenia associated infection rates in elderly AML patients in vivo. Clinical impact of the ATRA/AZA/PGZ treatment regimen is currently further investigated in a randomized clinical trial in chemorefractory AML patients (NCT02942758).