Association Between Early Hyperoxemia Exposure and Intensive Care Unit Mortality in Intracerebral Hemorrhage: An Observational Cohort Analysis.

BACKGROUND: Supraphysiologic levels of oxygen could have potential adverse effects on the brain that may be dose and time dependent in patients with brain injury. We therefore aimed to assess whether exposure to excess supplemental oxygen, measured as time-weighted mean exposure to hyperoxemia, was associated with intensive care unit (ICU) mortality in patients with intracerebral hemorrhage (ICH). METHODS: In this single-center retrospective cohort study, we included all patients admitted to our ICU with a diagnosis of primary spontaneous ICH. To provide a longitudinal measure of hyperoxemia exposure, we calculated the hyperoxemia dose, defined as the area under the partial pressure of oxygen in arterial blood (PaO2) time curve above the threshold PaO2 value of 100 mm Hg (13.3 kPa) divided by the number of hours of potential exposure. To provide consistent potential exposure windows and limit bias from informative censoring, nested subsets were created with progressively longer exposure periods (0-1 day, 0-2 days, 0-3 days, 0-4 days, 0-5 days, 0-6 days, 0-7 days). We used multivariable Cox regression, with hyperoxemia dose as a time-dependent covariate, to model ICU mortality. Admission ICH and Acute Physiology and Chronic Health Evaluation II scores were included as predictor covariables. A step-function extended Cox model was also fitted. RESULTS: Between September 2019 and July 2022, 275 patients met the inclusion criteria, with 24,588 arterial blood gas results available for analysis. The mean age was 57.19 years (± 13.99), 59.64% were male, 23.64% had an infratentorial origin of hemorrhage, and ICU mortality was 35.64%. Almost all patients (97.45%) were exposed to hyperoxemia during their ICU admission. Cox regression modeling showed an association between hyperoxemia dose and ICU mortality (hazard ratio 1.15, confidence interval 1.05-1.25, p = 0.003). This association was observed in the 0-1 day subset in the step-function extended Cox model (hazard ratio 1.19, confidence interval 1.06-1.35, p = 0.005) but not in any of the subsequent exposure periods. CONCLUSIONS: In patients with ICH admitted to the ICU, we observed an association between hyperoxemia dose and ICU mortality. Further prospective study is required to inform guidance on early systemic oxygen targets in ICH.

Early reduction in tumour [18F]fluorothymidine (FLT) uptake in patients with non-small cell lung cancer (NSCLC) treated with radiotherapy alone.

PURPOSE: Changes in tumour 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) uptake during concurrent chemo-radiotherapy in patients with non-small cell lung cancer (NSCLC) have been reported, at variable time points, in two pilot positron emission tomography (PET) studies. The aim of this study was to assess whether FLT changes occur early in response to radiotherapy (RT) without concurrent chemotherapy and whether such changes exceed test-retest variability. METHODS: Sixteen patients with NSCLC, scheduled to have radical RT, underwent FLT PET once/twice at baseline to assess reproducibility and/or after 5-11 RT fractions to evaluate response. Primary and nodal malignant lesions were manually delineated on CT and volume, mean and maximum standardized uptake values (SUV(mean) and SUV(max)) estimated. Analysis included descriptive statistics and parameter fitting to a mixed-effects model accounting for patients having different numbers of evaluable lesions. RESULTS: In all, 35 FLT PET scans from 7 patients with a total of 18 lesions and 12 patients with a total of 30 lesions were evaluated for reproducibility and response, respectively. SUV(mean) reproducibility in primary tumours (SD 8.9%) was better than SUV(max) reproducibility (SD 12.6%). In nodes, SUV(mean) and SUV(max) reproducibilities (SD 18.0 and 17.2%) were comparable but worse than for primary tumours. After 5-11 RT fractions, primary tumour SUV(mean) decreased significantly by 25% (p = 0.0001) in the absence of significant volumetric change, whereas metastatic nodes decreased in volume by 31% (p = 0.020) with a larger SUV(mean) decrease of 40% (p < 0.0001). Similar changes were found for SUV(max). CONCLUSION: Across this group of NSCLC patients, RT induced an early, significant decrease in lesion FLT uptake exceeding test-retest variability. This effect is variable between patients, appears distinct between primary and metastatic nodal lesions, and in primary tumours is lower than previously reported for concurrent chemo-RT at a similar time point. These results confirm the potential for FLT PET to report early on radiation response and to enhance the clinical development of novel drug-radiation combinations by providing an interpretable, early pharmacodynamic end point.

Successful Kidney Transplant from Donors with Sickle Cell Disease: A Case Series of Six Transplants.

People with sickle cell disease experience a high incidence of chronic kidney disease and end-stage kidney disease, secondary to tubular and glomerular effects of vaso-occlusion-induced hypoxia. Because of concerns of suboptimal kidney function, sickle cell donors are usually not considered for kidney donation, even if the rest of the parameters are acceptable for organ donation. A significant gap exists between the number of organ donors and the number of candidates waiting for a kidney transplant in the United States. To bridge the gap, we need to consider using nontraditional donors. We report kidney transplant outcomes in 6 recipients from 4 sickle cell kidney donors. Intracranial hemorrhage and sepsis were the causes of the death in donors, and no donor was in sickle cell crisis at the time of donation. None of the recipients experienced delayed graft function, and all recipients achieved excellent allograft function. The earliest allograft failure was at 27 months in a recipient who developed early acute rejection, while the longest follow-up was 10 years with adequate kidney function. In conclusion, given the shortage of kidneys for transplantation and demonstrated good outcomes, we propose that kidneys from sickle cell donors can be safely used.

Repurposing a Neurocritical Care Unit for the Management of Severely Ill Patients With COVID-19: A Retrospective Evaluation.

BACKGROUND: The World Health Organisation declared a coronavirus disease 2019 (COVID-19) pandemic on March 11, 2020. Following activation of the UK pandemic response, our institution began planning for admission of COVID-19 patients to the neurointensive care unit (neuro-ICU) to support the local critical care network which risked being rapidly overwhelmed by the high number of cases. This report will detail our experience of repurposing a neuro-ICU for the management of severely ill patients with COVID-19 while retaining capacity for urgent neurosurgical and neurology admissions. METHODS: We conducted a retrospective process analysis of the repurposing of a quaternary level neuro-ICU during the early stages of the COVID-19 pandemic in the United Kingdom. We retrieved demographic data, diagnosis, and outcomes from the electronic health care records of all patients admitted to the ICU between March 1, 2020 and April 30, 2020. Processes for increase in surge capacity, reduction in ICU demand, and staff redeployment and rapid training are reported. RESULTS: Over a 10-day period, total ICU capacity was increased by 21.7% (from 23 to 28 beds) while the capacity to provide mechanical ventilation was increased by 77% (from 13 to 23 beds). There were 30 ICU admissions of 29 COVID-19 patients between March 1 and April 30, 2020; median (range) length of ICU stay was 9.9 (1.3 to 32) days, duration of mechanical ventilation 11 (1 to 27) days, and ICU mortality rate 41.4%. There was a 44% reduction in urgent neurosurgical and neurology admissions compared with the same period in 2019. CONCLUSIONS: It is possible to repurpose a dedicated neuro-ICU for the management of critically ill non-neurological patients during a pandemic response, while maintaining access for urgent neuroscience referrals.

The effect of angiotensin-converting enzyme genotype on acute mountain sickness and summit success in trekkers attempting the summit of Mt. Kilimanjaro (5,895 m).

The I-allele rather than the D-allele of the human angiotensin converting enzyme (ACE) gene has been associated with high-altitude mountaineering success. We investigated whether the I-allele was associated with summit success, and also with AMS development, in altitude-naïve trekkers. Subjects ascended from 1,860 m to the summit over 4 days (n = 34, 'direct-profile') or 5 days (n = 82, 'slower-profile'). Proportionally more II direct-profile subjects were successful than ID or DD, although the difference was not significant (100% of II subjects, 52% ID and 43% DD, P = 0.09). There was no difference in success amongst subjects on the slower-profile (50% II, 45% ID and 58% DD, P = 0.54). There was a non-significant trend for increasing AMS scores in ID/DD subjects. Amongst tourist trekkers on Mt. Kilimanjaro the I-allele is not associated with summit success. No evidence is found to support an association between ACE genotype and AMS development.

Determinants of summiting success and acute mountain sickness on Mt Kilimanjaro (5895 m).

OBJECTIVE: To determine the incidence of acute mountain sickness (AMS), the frequency of summiting success, and the factors that affect these in trekkers on Kilimanjaro, one of the world's most summitted high-altitude peaks. METHODS: The study group comprised 312 trekkers attempting Mt Kilimanjaro summit by the Marango Route. Trekkers ascended over 4 or 5 days along a fixed ascent profile, stopping at 3 huts on ascent (2700 m, 3700 m, and 4700 m) before attempting the summit. Researchers were stationed at each hut for 16 days. Each night we measured heart rate, respiratory rate, blood pressure, oxygen saturation, and Lake Louise Score. We recorded the highest altitude that trekkers reached on the mountain. RESULTS: Of 181 complete sets of data, 111 (61%) trekkers reached the summit, and 139 (77%) developed AMS. Physiological results were not related to summit success. The incidence of AMS and summiting success were similar in those on the 4- or 5-day route. Trekkers on the 5-day route who used acetazolamide were less likely to develop AMS and more likely to summit than were those not taking acetazolamide (P = <.05); this difference was not present with trekkers on the 4-day route. CONCLUSIONS: The risk of developing AMS is high on Mt Kilimanjaro. Although taking an extra day to acclimatize with the use of acetazolamide did provide some protection against AMS, ideally trekkers need a more gradual route profile for climbing this mountain.

Outcomes with split liver transplantation are equivalent to those with whole organ transplantation.

BACKGROUND: Split liver transplantation is an excellent option for expansion of the donor organ pool. However, reports of increased morbidity in split liver recipients may limit use of this technique. STUDY DESIGN: This was a single center retrospective analysis investigating split liver transplantation. Between August 1, 1995 and March 30, 2012, 53 of 1,261 (4.2%) recipients received split liver grafts. RESULTS: The 1-, 5-, and 10-year patient and graft survivals in adult recipients of split grafts were 95.5%, 89.5%, and 89.5%, respectively. Survival was similar to that of whole organ recipients (p = 0.15). Twenty-three adults received split grafts: 18 (78%) were right trisegment grafts, 4 (17.4%) were right lobes, and 1 (4.3%) was a left lobe. The mean cold ischemic time was 5.7 hours (±2.4 hours [SD]) and warm ischemic time was 36 minutes (±5.5 minutes). Four (17%) recipients required hepatic artery reconstruction; 5 (21.7%) required a caval-venous patch, and 5 (21.7%) had Roux-en-Y reconstruction of the bile duct. No venous conduits were required. Thirty children received split grafts (median age 1.2 years, range 0.1 to 16.4 years) and had a median weight of 8.6 kg (range 3.6 to 45 kg). Pediatric split 1-, 5-, and 10-year overall and graft survival rates were 96.7%, 80.0%, 80.0%, and 93.3%, 76.8, and 76.8%, respectively. Complications included retransplantation in 3 (10.0%), bile leak in 5 (16.7%), hepatic arterial thrombosis in 2 (6.7%), bowel perforation in 2 (6.7%), and bleeding in 2 (6.7%). The mean donor age was 22.4 months (±8.9) months and body mass index was 22.8 kg/m(2) (±3.3 kg/m(2)). CONCLUSIONS: We demonstrated excellent outcomes in adult and pediatric recipients using carefully selected donors for liver splitting. We recommend escalation of the use of split liver transplants to expand the donor pool for cadaveric liver transplantation.