Early administration of umbilical cord blood cells following brief high tidal volume ventilation in preterm sheep: a cautionary tale.

BACKGROUND: Umbilical cord blood (UCB) cells are a promising treatment for preterm brain injury. Access to allogeneic sources of UCB cells offer the potential for early administration to optimise their therapeutic capacities. As preterm infants often require ventilatory support, which can contribute to preterm brain injury, we investigated the efficacy of early UCB cell administration following ventilation to reduce white matter inflammation and injury. METHODS: Preterm fetal sheep (0.85 gestation) were randomly allocated to no ventilation (SHAM; n = 5) or 15 min ex utero high tidal volume ventilation. One hour following ventilation, fetuses were randomly allocated to i.v. administration of saline (VENT; n = 7) or allogeneic term-derived UCB cells (24.5 ± 5.0 million cells/kg; VENT + UCB; n = 7). Twenty-four hours after ventilation, lambs were delivered for magnetic resonance imaging and post-mortem brain tissue collected. Arterial plasma was collected throughout the experiment for cytokine analyses. To further investigate the results from the in vivo study, mononuclear cells (MNCs) isolated from human UCB were subjected to in vitro cytokine-spiked culture medium (TNFα and/or IFNγ; 10 ng/mL; n = 3/group) for 16 h then supernatant and cells collected for protein and mRNA assessments respectively. RESULTS: In VENT + UCB lambs, systemic IFNγ levels increased and by 24 h, there was white matter neuroglial activation, vascular damage, reduced oligodendrocytes, and increased average, radial and mean diffusivity compared to VENT and SHAM. No evidence of white matter inflammation or injury was present in VENT lambs, except for mRNA downregulation of OCLN and CLDN1 compared to SHAM. In vitro, MNCs subjected to TNFα and/or IFNγ displayed both pro- and anti-inflammatory characteristics indicated by changes in cytokine (IL-18 & IL-10) and growth factor (BDNF & VEGF) gene and protein expression compared to controls. CONCLUSIONS: UCB cells administered early after brief high tidal volume ventilation in preterm fetal sheep causes white matter injury, and the mechanisms underlying these changes are likely dysregulated responses of the UCB cells to the degree of injury/inflammation already present. If immunomodulatory therapies such as UCB cells are to become a therapeutic strategy for preterm brain injury, especially after ventilation, our study suggests that the inflammatory state of the preterm infant should be considered when timing UCB cells administration.

Serum potassium changes during hypothermia and rewarming: a case series and hypothesis on the mechanism.

Introduction: Hypokalemia is known to occur in association with therapeutically induced hypothermia and is usually managed by the administration of potassium (K+). Methods: We reviewed data from 74 patients who underwent a therapeutic hypothermia protocol at our medical institution. Results: In four patients in whom data on serum K+ and temperature were available, a strong positive correlation between serum K+ and body temperature was found. Based on the close positive relationship between serum K+ and total body temperature, we hypothesize that serum K+ decreases during hypothermia owing to decreased activity of temperature-dependent K+ exit channels that under normal conditions are sufficiently active to match cellular K+ intake via sodium/K+/adenosine triphosphatase. Upon rewarming, reactivation of these channels results in a rapid increase in serum K+ as a result of K+ exit down its concentration gradient. Conclusion: Administration of K+ during hypothermia should be done cautiously and avoided during rewarming to avoid potentially life-threatening hyperkalemia. K+ exit via temperature-dependent K+ channels provides a logical explanation for the rebound hyperkalemia. K+ exit channels may play a bigger role than previously appreciated in the regulation of serum K+ during normal and pathophysiological conditions.

Meta-Analysis of the Use of Head Impulse Test and Head Impulse Test with Direction Changing Nystagmus and Test of Skew Deviation in the Diagnosis of Peripheral Vertigo and Stroke.

INTRODUCTION: The head impulse test (HIT) and HIT combined with direction-changing Nystagmus-Test of Skew deviation (HINTS) have been proposed as bedside tests to differentiate between peripheral and central causes of vertigo in the emergency department (ED). We conducted a meta-analysis of the HIT and HINTS tests to diagnose peripheral vertigo (PV) and central vertigo. METHODS: Pubmed, Google Scholar, EmBase, and articles references published in English up to July 2021 were searched for keywords "vertigo" or "acute vestibular syndrome" or "dizziness" and "head impulse" and "stroke." The bivariate method for meta-analysis was used to calculate positive (PLR) and negative likelihood ratios (NLR) and summary receiver operating characteristics area under the curve (AUC). RESULTS: A total of 11 studies were included analysing both HIT (8 studies, N = 417) and HINTS (6 studies, N = 405). HIT and HINTS were performed within 24 h in 4 of 11 studies. PLR and NLR for HIT in PV was 4.85 (95% CI: 2.83-8.08) and 0.19 (95% CI: 0.12-0.29, I2 63.25%), respectively. The AUC for HIT the diagnosis of PV and stroke was 0.90 and 0.92, respectively. PLR and NLR for a negative HIT in stroke was 5.85 (95% CI: 3.07-10.6) and 0.17 (95% CI: 0.08-0.30), respectively. PLR and NLR for peripheral HINTS pattern for PV was 17.3 (95% CI: 8.38-32.1) and 0.15 (95% CI: 0.07-0.26), respectively. PLR and NLR for central HINTS pattern for stroke: 5.61 (95% CI: 4.19-7.7) and 0.06 (95% CI: 0.03-0.12). In all included studies, HIT and HINTS exams were administered by neurology residents or neurology specialists with additional neuro-otology or neuro-ophthalmology subspeciality experience, and two studies included ED physicians. Raters reported high degree of bias and high concern regarding applicability in most domains of the quality assessment of diagnostic accuracy studies (QUADAS-2) tool. Meta-regression did not demonstrate a statistically significant effect of publication year, time to test, and type of assessor on sensitivity or false positive rate. CONCLUSION: The HIT and HINTS exams appear to be moderately good discriminators of central and PV. However, in most papers, the tests were administered by neurologists and were evaluated beyond 24 h, which may limit utility in the ED setting.

Initiation of maintenance hemodialysis through central venous catheters: study of patients' perceptions based on a structured questionnaire.

BACKGROUND: Despite well-publicized suggestions to utilize arteriovenous fistulae and grafts to initiate hemodialysis, too many patients in the United States start dialysis via central venous catheters despite their well-known association with increased morbidity, mortality, and cost. METHODS: To determine the reasons for this high rate of catheter use, and, ultimately, ways to reduce it, we developed a questionnaire designed to determine where in the process of patient care the process to fistula or graft placement was not completed, thus requiring the use of central venous catheters. The questionnaire was reviewed by several nephrologists not involved with the study. We administered the questionnaire to 52 consecutive hospitalized patients who started maintenance dialysis with catheters at a University-affiliated Hospital and referral center. The questionnaire asked each patient to provide details pertaining to pre-dialysis care, referrals, and follow-through on recommended referrals. If the patient did not see the physician to whom he/she was referred, we asked the reason(s) for such failure. RESULTS: Patient responses showed that there were two major lapses in the transition from diagnosis of advanced kidney disease to construction of appropriate dialysis access: failure by the patients to see a nephrologist and/or an access surgeon, and failure by physicians to refer patients to an access surgeon. Twenty percent of the patients failed to follow up with either a nephrologist or a surgeon. Only 38% (15/40) of those seen by a nephrologist had been referred to a surgeon. CONCLUSIONS: The quality of care was impaired by lack of referral to surgeons by nephrologists and by lack of follow-through by patients. Areas for improvement include improved communications between physicians and patients and more careful follow-up by both physicians and patients. Several methods of providing better patient care and communication between patients and nephrologists are recommended.

Conventional and sharp safety devices in 6 hospitals in British Columbia, Canada.

BACKGROUND: Reengineered sharp safety devices have been recommended to reduce occupational percutaneous injury risk in health care facilities. We conducted this study just over 1 year after passage of legislation requiring the use of sharp safety medical devices to assess the frequency of safety and conventional sharp device use and whether safety features were being activated to cover sharp points after safety devices were used and before disposal. METHODS: Approximately equal numbers of sharps disposal containers from various wards in 6 nonprofit adult and pediatric British Columbia hospitals were audited by paired research assistants, wearing protective clothing. RESULTS: In the 699 audited sharps containers, 7% (1,690/25,910) of all devices were conventional devices, specifically 2% (96/4,702) of all phlebotomy devices, 7% (1,240/17,705) of all syringes, and 10% (354/3,503) of all intravenous catheters. In addition, 94% (4,344/4,602) of all safety phlebotomy devices, 95% (2,955/3,119) of all safety intravenous devices, and 80% (13,050/16,420) of all safety syringes had been activated before disposal. CONCLUSION: More than 1 year after legislation was passed mandating the use of sharp safety devices in British Columbia hospitals, the risk from sharps remains excessive because of the ongoing use of conventional sharp devices and nonactivation of safety devices.