Approval rates for corneal donation and the origin of donor tissue for transplantation at a university-based tertiary referral center with corneal subspecialization hosting a LIONS Eye Bank

Background With the increasing demand for corneas, eye banks must optimize the tissue donation, collection, and selection process. This retrospective monocentric study analyzed the approval rates for corneal donation and the origin of and reasons for discarding donor corneas from 2010 to 2019. Methods Data included the number of deceased, approval or rejection by the family for corneal donation and contraindications. Corneal grafts were included from all deceased persons who were full-body and multi-organ donors at the Saarland University Medical Center (UKS) and from external institutions. Additional analyzed parameters included endothelial cell count (ECC), blood sample serology for infections, and conjunctival swab testing . Results A total of 1748 corneoscleral buttons were harvested from 10,265 deceased persons (17% with no contraindication) at the UKS between 2010 and 2019, with a consent rate of 23.3%. The number of keratoplasties increased from 136 in 2010 (15% of the deceased, total = 925) to 251 in 2019 (21%, total = 1214). Both the general and department-specific data showed similar percentages for corneal donation over the years, with intensive care and palliative units recently providing the most corneas. The increase in the number of corneas processed by the cornea bank over the years (368 in 2010 compared with 857 in 2019) was linked both to a better internal supply in 2010 (262, 71.2% of the total) compared with 2019 (519, 60.6%) and to an external supply by reinforcement of cooperation with external hospitals, including Luxembourg in 2010 (106, 28.8% of the total) compared with 2019 (338, 39.4%). A total of 195 of 377 corneas (52%) were discarded in 2009 compared with 260 out of 715 (36%) in 2019. The main reasons for discarding were low ECC (36% of discarded corneas in 2009; 11% in 2019), positive conjunctival swab (11% in 2009; 13% in 2019), and blood sample serology (6% in 2009 and in 2019). Conclusion Despite an increasing number of donors, the demand for corneas is still rising. Improved cooperation with internal departments and with external clinics has led to an increasing number of explanted corneas. The main reason for discarding corneas was low ECC, followed by a positive conjunctival swab for fungal or bacterial contamination and serology. Increased donation rates and continued improvements in collection and selection processes are necessary to cover the high demand for corneas.

Identification of domestic cat hepadnavirus from a cat blood sample in Japan

The hepatitis B virus (Hepadnaviridae) induces chronic hepatitis and hepatic cancer in humans. A novel domestic cat hepadnavirus (DCH) was recently identified in several countries, however, the DCH infection status of cats in Japan is unknown. Therefore, we investigated the DCH infection rate of 139 cat samples collected in Japan. We identified one positive blood sample (0.78%) from a 17-year-old female cat with chronically elevated alanine aminotransferase. Phylogenetic analysis demonstrated that the DCH strain identified in this study is genetically distinct from strains in other countries. Further investigations are required to elucidate the evolution of DCH and the impact of DCH infection on hepatic diseases in domestic cats.

Face Validity of Observed Meal Patterns Reported with 7-Day Diet Diaries in a Large Population-Based Cohort Using Diurnal Variation in Concentration Biomarkers of Dietary Intake

In a cross-sectional analysis of a population-based cohort (United Kingdom, N = 21,318, 1993–1998), we studied how associations between meal patterns and non-fasting triglyceride and glucose concentrations were influenced by the hour of day at which the blood sample was collected to ascertain face validity of reported meal patterns, as well as the influence of reporting bias (assessed using formula of energy expenditure) on this association. Meal size (i.e., reported energy content), mealtime and meal frequency were reported using pre-structured 7-day diet diaries. In ANCOVA, sex-specific means of biomarker concentrations were calculated by hour of blood sample collection for quartiles of reported energy intake at breakfast, lunch and dinner (meal size). Significant interactions were observed between breakfast size, sampling time and triglyceride concentrations and between lunch size, sampling time and triglyceride, as well as glucose concentrations. Those skipping breakfast had the lowest triglyceride concentrations in the morning and those skipping lunch had the lowest triglyceride and glucose concentrations in the afternoon, especially among acceptable energy reporters. Eating and drinking occasion frequency was weakly associated with glucose concentrations in women and positively associated with triglyceride concentrations in both sexes; stronger associations were observed for larger vs. smaller meals and among acceptable energy reporters. Associations between meal patterns and concentration biomarkers can be observed when accounting for diurnal variation and underreporting. These findings support the use of 7-day diet diaries for studying associations between meal patterns and health.

Gluten-related immunogenic peptides in stool as means to monitor compliance with gluten-free diet in children with newly dia gnosed coeliac disease

Objectives and study: To compare the values of gluten-related immunogenic peptides (GIP) in stool and anti-tissue transglutaminase IgA antibodies (anti-tTG IgA) in blood in children newly diagnosed with coeliac disease (CD). Methods: All children (2–15 y) newly diagnosed with CD between May 2018 and May 2020 at our clinic who complied with the inclusion criteria were invited to join the prospective study. During workup for CD, a stool sample to measure GIP was taken together with a blood sample to measure anti-tTG IgA. All newly diagnosed children were invited 4 months later for a check-up. Children and their caregivers were asked about known non-compliance with the gluten-free diet (GFD), a blood sample was taken to measure the anti-tTG IgA, and a stool sample was collected to measure GIP. Blood was evaluated for anti-tTG IgA by ELISA, and the stool was tested by quantitative Sandwich ELISA designed to detect and quantify GIP using the G12 antibody. Values of GIP and anti-tTG IgA were compared in terms of their relation to the upper limit of normal (ULN) of the particular method. Results: 29 children (18 girls) were enrolled in the study. The values of GIP in stool at the time of diagnosis were above the ULN (0.15 µg/g) in all children. Average 4.21, median 3.29, standard deviation (SD) 3.7. After the four months, all but three (89.7%) had values of GIP in the reference range. Average 0.29, median 0.12, SD 0.73. Similarly, anti-tTG IgA values were above the ULN (9.9 U/mL) at the time of diagnosis in all children. Average 164, median 195, SD 49. Although the anti-tTG IgA levels were lower at check-up in all but one child, only 10 (34.5%) showed values within the normal range, with an average of 27.9, median 12.0, and SD 38.9. All children declared strict adherence to GFD. Discussion: Using the GIP concentration in stool, adherence to GFD in our cohort of children is very good, better than that described in literature. Conclusion: Measuring GIP in stool could prove a more sensitive indicator of adherence to GFD in the early months after the diagnosis of CD when anti-tTG IgA are still elevated above the ULN due to their well-described gradual decrease after GFD initiation.

Gluteal Compartment Syndrome and Rhabdomyolysis after Prolonged Laparoscopic Nephroureterectomy and Treatment Strategies Including Rehabilitation: A Case Report

Background: Rhabdomyolysis is a clinical symptom caused by the rapid release of intracellular components such as myoglobin, lactate dehydrogenase, and creatine kinase into the blood circulation. It is commonly caused by muscular injury including compartment syndrome, infection, drugs, etc. Although it rarely occurs during surgery, the incidence may increase if risk factors such as long operation time, improper posture, and condition of being overweight exist. Case Presentation: A 46-year-old male patient complained of pain and weakness in the right hip area and several abnormal findings were observed in the blood sample, reflecting muscle injury and decreased renal function after prolonged urological surgery. He was confirmed as having rhabdomyolysis, which was caused by compartment syndrome of the right gluteal muscle. After the diagnosis, conservative cares were performed in the acute phase and rehabilitation treatments were performed in the chronic phase. After conservative treatment and rehabilitation, blood sample values returned to almost normal ranges and both level of pain and muscle strength were significantly improved. In addition, about 25 days after discharge, he almost recovered to pre-operative condition. Conclusion: Careful attention is required to prevent intraoperative compartment syndrome. It also suggests that not only medical treatment but also early patient-specific rehabilitation is important in patients with rhabdomyolysis after prolonged surgery.

Proficiency-based progression intern training to reduce critical blood sampling errors including ‘wrong blood in tube’

Background: Blood sampling errors including ‘wrong blood in tube’ (WBIT) may have adverse effects on clinical outcomes. WBIT errors occur when the blood sample in the tube is not that of the patient identified on the label. This study aims to determine the effect of proficiency-based progression (PBP) training in phlebotomy on the rate of blood sampling errors (including WBIT). Methods: A non-randomised controlled trial compared the blood sampling error rate of 43 historical controls who had not undergone PBP training in 2016 to 44 PBP trained interventional groups in 2017. In 2018, the PBP training programme was implemented and the blood sampling error rate of 46 interns was compared to the 43 historical controls in 2016. Data analysis was performed using logistic regression analysis adjusting for sample timing. Results: In 2016, 43 interns had a total blood sample error rate of 2.4%, compared to 44 interns in 2017, who had error rate of 1.2% (adjusted OR=0.50, 95% CI 0.36-0.70; <0.01). In 2018, 46 interns had an error rate of 1.9% (adjusted OR=0.89, 95% CI 0.65-1.21; p=0.46) when compared to the 2016 historical controls. There were three WBITs in 2016, three WBITs in 2017 and five WBITs in 2018. Conclusions: The study demonstrates that PBP training in phlebotomy has the potential to reduce blood sampling errors. Trial registration number: NCT03577561

CHANGES IN SERUM LEVELS OF BRAIN-DERIVED NEUROTROPHIC FACTOR WITH ELECTROCONVULSIVE THERAPY AND PHARMACOTHERAPY AND ITS CLINICAL CORRELATES IN MALE SCHIZOPHRENIA PATIENTS

Objectives: It has been postulated that neurotrophin dysregulation leads to disorganization in neuronal networks, which results in schizophrenia. The current study sets out to evaluate if the finding of lower BDNF levels in schizophrenia patients could be confirmed in an independent cohort, and to investigate if the BDNF levels can be altered with different treatment modalities such as electroconvulsive therapy (ECT) and/or antipsychotic pharmacotherapy (PT). Methods: A total of 54 male patients with schizophrenia and 35 healthy controls were included in the study. Schizophrenia patients were subdivided into two groups as the ones who underwent ECT+PT and only PT. Clinical and sociodemographic data questionnaire, Positive and Negative Syndrome Scale (PANSS) and blood sample collection for BDNF assessment were applied to all patients (on first and last days of admissions) and healthy participants (on the day of the interview). Then, clinical parameters and blood sample outcomes were statistically analyzed. Results: Mean BDNF levels of healthy individuals was significantly higher than mean pre and post-treatment BDNF levels in both PT only and ECT+PT groups. While serum BDNF levels did not increase after ECT+PT, there was a trend level increase in the PT only group. There was no significant correlation between the change in serum BDNF levels with total PANSS scores in either group after treatment. Conclusions: We could confirm previously suggested data of lower serum BDNF levels in schizophrenia patients compared to healthy population but we couldn’t find significant increase in serum BDNF levels with ECT+PT or only PT as some previous studies suggested.

Dose-Response of Paraxanthine on Cognitive Function: A Double Blind, Placebo Controlled, Crossover Trial

Paraxanthine (PXN) is a metabolite of caffeine that has recently been reported to enhance cognition at a dose of 200 mg. Objective: To determine the acute and short-term (7-day) effects of varying doses of PXN on cognitive function and side effects. Methods: In a double blind, placebo-controlled, crossover, and counterbalanced manner, 12 healthy male and female volunteers (22.7 ± 4 years, 165 ± 7 cm, 66.5 ± 11 kg, 24.4 ± 3 kg/m2) ingested 200 mg of a placebo (PLA), 50 mg of PXN (ENFINITY™, Ingenious Ingredients, L.P.) + 150 mg PLA, 100 mg PXN + 100 mg PLA, or 200 mg of PXN. With each treatment experiment, participants completed side effect questionnaires and donated a fasting blood sample. Participants then performed a series of tests assessing cognition, executive function, memory, and reaction time. Participants then ingested one capsule of PLA or PXN treatments. Participants then completed side effects and cognitive function tests after 1, 2, 3, 4, 5, and 6 h of treatment ingestion. Participants continued ingesting one dose of the assigned treatment daily for 6-days and returned to the lab on day 7 to donate a fasting blood sample, assess side effects, and perform cognitive function tests. Participants repeated the experiment while ingesting remaining treatments in a counterbalanced manner after at least a 7-day washout period until all treatments were assessed. Results: The Sternberg Task Test (STT) 4-Letter Length Present Reaction Time tended to differ among groups (p = 0.06). Assessment of mean changes from baseline with 95% CI’s revealed several significant differences among treatments in Berg-Wisconsin Card Sorting Correct Responses, Preservative Errors (PEBL), and Preservative Errors (PAR Rules). There was also evidence of significant differences among treatments in the Go/No-Go Task tests in Mean Accuracy as well as several time points of increasing complexity among STT variables. Finally, there was evidence from Psychomotor Vigilance Task Test assessment that response time improved over the series of 20 trials assessed as well as during the 6-h experiment in the PXN treatment. Acute and short-term benefits compared to PLA were seen with each dose studied but more consistent effects appeared to be at 100 mg and 200 mg doses. No significant differences were observed among treatments in clinical chemistry panels or the frequency or severity of reported side effects. Results provide evidence that acute ingestion of 100 mg and 200 mg of PXN may affect some measures of cognition, memory, reasoning, and response time as well as help sustain attention. Additionally, that acute and daily ingestion of PXN for 7 days is not associated with any clinically significant side effects. Conclusions: PXN may serve as an effective nootropic agent at doses as low as 50 mg.

Comparison of the effect of three intramuscular sedation protocols on packed cell volume and total protein in cats

Objectives The aim of this study was to evaluate the change in packed cell volume (PCV) and total protein following intramuscular preanesthetic sedation with one of three drug combinations in cats. Methods Thirty client-owned cats were enrolled in this prospective, randomized, blinded, clinical study. A venous blood sample was obtained prior to administration of any sedation and PCV, total protein, electrolytes (Na+, K+, Cl–, iCa2+), glucose and lactate were measured. Cats were randomly assigned to receive one of three intramuscular sedation protocols (n = 10 cats/protocol): methadone 0.2 mg/kg + acepromazine 0.02 mg/kg (MA), methadone 0.2 mg/kg + dexmedetomidine 5 µg/kg (MD) or methadone 0.2 mg/kg + midazolam 0.2 mg/kg + alfaxalone 2 mg/kg (MMA). Twenty-five minutes later, cats were assessed for level of sedation followed by another venous blood sampling to evaluate the same variables as above. Results There were no significant differences in demographics (age, weight, sex) between groups. Level of sedation was significantly higher in MMA cats. Within groups, after premedication, PCV and hemoglobin significantly decreased in all groups, total protein significantly decreased in the MA and MMA groups and glucose significantly increased in the MD group. For electrolytes, statistical changes were not clinically relevant; Cl– mean difference was significantly different between MA and MD; in the MD group Na+ and Cl– significantly decreased and in the MMA group Cl– significantly increased. Conclusions and relevance All three sedation protocols caused significant decreases in PCV and hemoglobin in healthy cats.