Corrigendum: Ex vivo normothermic preservation of a kidney graft from uncontrolled donation after circulatory death over 73 hours.

[This corrects the article DOI: 10.3389/fbioe.2023.1330043.].

Transplantation of organs from SARS-CoV-2-positive donors: Preliminary experience from Spain.

BACKGROUND: The utilization of non-lung organs from deceased donors with a positive polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the time of donation can be lifesaving, although the safety of this policy must be assessed. METHODS: This is a nationwide, prospective study, reporting the experience on the utilization of non-lung organs from SARS-CoV-2-positive donors between December 15, 2020 and May 31, 2022 in Spain. RESULTS: A total of 69 patients received a solid organ transplant (41 kidney, 18 liver, 8 heart, and 2 combined liver-kidney) obtained from 32 donors with a positive SARS-CoV-2 PCR at the time of donation (four of them with a cycle threshold value <30). All recipients tested negative for SARS-CoV-2 and were free of coronavirus disease 2019 (COVID-19) symptoms prior to transplantation. Nasopharyngeal swab turned positive for SARS-CoV-2 PCR in 4 (5.8%) recipients at 3, 8, 11, and 20 days after transplantation, though evidence did not support a donor-derived COVID-19. Four kidney recipients lost their grafts and two patients died: one heart recipient due to cardiogenic shock and one combined liver-kidney recipient due to lung hypertension and right heart failure. Graft losses and patient deaths were deemed unrelated to the donor SARS-CoV-2 status by the treating teams. No other adverse reactions were reported. CONCLUSIONS: This preliminary experience supports the safety of the use of organs other than lungs from SARS-CoV-2 PCR-positive donors, in alignment with previous series. However, the impact of SARS-CoV-2 infection upon organ quality should be established in future research.

Ex vivo normothermic preservation of a kidney graft from uncontrolled donation after circulatory death over 73 hours.

The transplant community is focused on prolonging the ex vivo preservation time of kidney grafts to allow for long-distance kidney graft transportation, assess the viability of marginal grafts, and optimize a platform for the translation of innovative therapeutics to clinical practice, especially those focused on cell and vector delivery to organ conditioning and reprogramming. We describe the first case of feasible preservation of a kidney from a donor after uncontrolled circulatory death over a 73-h period using normothermic perfusion and analyze hemodynamic, biochemical, histological, and transcriptomic parameters for inflammation and kidney injury. The mean pressure and flow values were 71.24 ± 9.62 mmHg and 99.65 ± 18.54 mL/min, respectively. The temperature range was 36.7°C-37.2°C. The renal resistance index was 0.75 ± 0.15 mmHg/mL/min. The mean pH was 7.29 ± 0.15. The lactate concentration peak increased until 213 mg/dL at 6 h, reaching normal values after 34 h of perfusion (8.92 mg/dL). The total urine output at the end of perfusion was 1.185 mL. Histological analysis revealed no significant increase in acute tubular necrosis (ATN) severity as perfusion progressed. The expression of KIM-1, VEGF, and TGFß decreased after 6-18 h of perfusion until 60 h in which the expression of these genes increased again together with the expression of ß-catenin, Ki67, and TIMP1. We show that normothermic perfusion can maintain a kidney graft viable ex vivo for 3 days, thus allowing a rapid translation of pre-clinical therapeutics to clinical practice.

Clinical Utility and Evolution of Donor Serum Lactate During Normothermic Regional Perfusion in Uncontrolled Donation After Circulatory Death.

BACKGROUND: Kidney transplantation from uncontrolled donor after circulatory death (uDCD) showed a higher incidence of delayed graft function and primary failure. The aim of this study was to study basal and kinetic evolution of lactate values in uDCD preserved on normothermic regional perfusion (NRP) as a predictive factor of kidney suitability exposed to prolong ischemic conditions. METHODS: Descriptive and prospective study of a cohort of out-of-hospital cardiac arrest patients admitted to the emergency room as potential uDCD. Donors meeting the inclusion criteria were preserved on NRP for at least 2 hours before procurement. Serum lactate levels were determined at arrival as basal level and at 30 minutes intervals and compared with adequate renal perfusion in the operating room (OR). RESULTS: Forty-five donors met inclusion criteria. Of these, 38 went to the OR (84.5%). No differences were found in basal lactate between accepted and rejected kidneys (203.08 ± 59.21 vs 175.43 ± 75.32 mg/dL, respectively); neither lactate, hematologic, hepatic transaminases, creatinine, or blood gas analysis sequential values evolved while on NRP. Lactate receiver operating characteristic curve failed to predict viability at different time points and did not correlate with the macroscopic kidney poor perfusion in the OR. CONCLUSIONS: The baseline and kinetic evolution of plasma lactate values while on NRP, were not useful tools to predict the final OR kidney viability owing to previous severe ischemic insult.

Double hemispheric Microdialysis study in poor-grade SAH patients.

Delayed cerebral ischemia (DCI) is a dreadful complication present in 30% of subarachnoid hemorrhage (SAH) patients. DCI prediction and prevention are burdensome in poor grade SAH patients (WFNS 4-5). Therefore, defining an optimal neuromonitoring strategy might be cumbersome. Cerebral microdialysis (CMD) offers near-real-time regional metabolic data of the surrounding brain. However, unilateral neuromonitoring strategies obviate the diffuse repercussions of SAH. To assess the utility, indications and therapeutic implications of bilateral CMD in poor grade SAH patients. Poor grade SAH patients eligible for multimodal neuromonitoring were prospectively collected. Aneurysm location and blood volume were assessed on initial Angio-CT scans. CMD probes were bilaterally implanted and maintained, at least, for 48 hours (h). Ischemic events were defined as a Lactate/Pyruvate ratio >40 and Glucose concentration <0.7 mmol/L. 16 patients were monitored for 1725 h, observing ischemic events during 260 h (15.1%). Simultaneous bilateral ischemic events were rare (5 h, 1.9%). The established threshold of ≥7 ischemic events displayed a specificity and sensitivity for DCI of 96.2% and 83.3%, respectively. Bilateral CMD is a safe and useful strategy to evaluate areas at risk of suffering DCI in SAH patients. Metabolic crises occur bilaterally but rarely simultaneously. Hence, unilateral neuromonitoring strategies underestimate the risk of infarction and the possibility to offset its consequences.

Severe and morbid obesity and transfusional risk in total knee arthroplasty: An observational study.

BACKGROUND: Severe and morbid obesity (Class II -III) represents a challenge for successful knee surgery. There isn't consensus on what influence body mass index has on blood loss and on red blood cell (RBC) transfusion during total knee arthroplasty (TKA). The objective was to determine blood loss and transfusion needs in severe and morbid obese patients undertaking TKA. METHODS: We recorded retrospectively all patients undergoing TKA. Obesity was assessed according to WHO guidelines. Perioperative haemoglobin and treatments for its optimisation were recorded. Blood losses were estimated from specific formulae for lost red-cell mass and percentage of lost blood volume. RESULTS: 922 patients were included: 35.90% were obese Class I and 18.76% obese Class II - III. Estimated blood volume was 4390  ±â€¯â€¯470 ml, 4736  ±â€¯â€¯423 ml and 5030 ±â€¯464 ml among non-obese, obese Class I and obese Class II-III, respectively (P < 0.001). The global estimated blood volume (EBV) lost was 1502  ±â€¯â€¯680 ml without differences between the three groups. However, the percentage of lost blood volume was lower in obese Class II -III (29.65%) than in non-obese (33.55%) and obese Class I (30.97%) (P < 0.005). Transfusion rates were 12.7%, 12.1% and 6.4% for non-obese, obese Class I and Class II -III, respectively (P = 0.062). A negative transfusion risk was predicted for Class II -III patients. CONCLUSIONS: Severely and morbidly obese patients did not show greater blood loss nor higher RBC transfusion needs after primary TKA than non-obese and obese Class I patients. This could be because obese Class II -III patients had higher EBV but similar RBC losses.

Cross-Sectional and Longitudinal Cognitive Correlates of FDDNP PET and CSF Amyloid-ß and Tau in Parkinson's Disease1.

Tau and amyloid-ß (Aß) aggregates have been suggested to play a role in the development of dementia in Parkinson's disease (PD). Positron emission tomography (PET) with [18F]FDDNP and the determination of cerebrospinal fluid (CSF) levels of these proteins constitute a means to visualize in vivo Aß and tau brain accumulation. Information about longitudinal changes of these CSF and PET biomarkers in PD with regard to progression to dementia is lacking. We assessed the cross-sectional and longitudinal associations of CSF and PET biomarkers of tau and Aß with PD-related cognitive dysfunction in 6 healthy-controls (HC), 16 patients with PD without dementia (PDND), and 8 PD with dementia (PDD). All subjects underwent comprehensive neuropsychological testing, [18F]FDDNP PET, and CSF Aß-tau determination. After 18 months, the PDND group was re-assessed clinically and by neuropsychological, PET, and CSF determinations. Cross-sectionally, PDD had higher [18F]FDDNP binding in lateral temporal regions and lower levels of CSF Aß levels compared to PDND, with a congruent correlation between the [18F]FDDNP binding and CSF Aß levels. Longitudinally, higher baseline lateral temporal [18F]FDDNP binding was associated to longitudinal worsening in cognitive performances and progression to dementia among subjects classified as PDND at baseline, who additionally disclosed at follow-up an increase in lateral-temporal FDDNP binding, as well as a reduction in CSF Aß and an increase in CSF tau levels. These results confirm the relevance of these CSF and PET biomarkers to PDD, being specifically the first to show [18F]FDDNP PET as a dementia risk biomarker in PD, along with longitudinal CSF and PET changes over time.

Perioperative hyperglycaemia and incidence of post-operative complications in patients undergoing total knee arthroplasty.

PURPOSE: The aim of this study was to assess whether hyperglycaemia in the post-operative period of total knee arthroplasty (TKA) affects post-operative complications regardless of diabetes mellitus (DM) diagnosis. METHODS: All patients who had undergone primary TKA were included in the study. The following data were recorded: DM diagnosis, and pre- (BGL1), intra- (BGL2) and post-operative blood glucose levels (BGL3). After 1-year follow-up, medical, infectious and mechanical or surgery-related complications were recorded. RESULTS: Of the 833 patients included, 130 (15.6 %) were diabetic. Median BGL1, BGL2 and BGL3 were 106.13, 93.49 and 134.16 mg/dl, respectively. After follow-up, 173 (20.8 %) patients presented complications, including 48 (5.76 %) medical complications and 94 (11.28 %) infections. Surgery-related complications presented in 31 (3.72 %) patients. A statistically significant association was found between BGL3 ≥ 126 mg/dl and complications (OR 1.95, p < 0.001), medical complications (OR 3.98, p < 0.001), and infections (OR 1.76, p < 0.006). CONCLUSIONS: Hyperglycaemia during the post-operative period in diabetic and non-diabetic patients undergoing TKA increases post-operative medical and infectious complications. Glycemic control during this period must be performed in order to reduce these complications. LEVEL OF EVIDENCE: Retrospective case series, Level IV.

Severe and morbid obesity (BMI ≥ 35 kg/m(2)) does not increase surgical time and length of hospital stay in total knee arthroplasty surgery.

PURPOSE: Certain aspects of total knee arthroplasty (TKA) in severely and morbidly obese (SMO) patients (BMI ≥ 35 kg/m(2)) remain controversial. This study aimed to assess the duration of TKA surgery and hospital stay in relation to patients' BMI. METHODS: Three operative times during TKA surgery were recorded: tourniquet time, to determine surgical difficulty, total surgical time, to assess the difficulty of achieving anaesthesia, and time in the surgical area, to assess patient management in the surgical area. Length of hospital stay was also calculated. Data were collected prospectively from consecutive patients and were recorded in a database for retrospective analysis. RESULTS: Data were obtained from 922 consecutive patients undergoing TKA. The non-obese group comprised 418 patients (45.3%), obese group Class I 331 (36%), and the SMO group (Class II-III) 173 (18.7%). Mean tourniquet time was 53 min, mean total surgical time was 84 min, and mean time in the surgical area was 132 min. There were no differences according to BMI group. Median length hospital stay (LHS) was 6 days in all patients regardless of BMI. Factors that significantly prolonged LHS were ASA III-IV and pre-operative haemoglobin between 12 and 13 g/dl. CONCLUSION: Severely and morbidly obese (SMO) patients (BMI ≥ 35 kg/m(2)) undergoing TKA surgery do not require longer operative time or hospital stay than non-obese or obese Class I patients. The fact that surgical time was not significantly different could be due to greater specialisation in the treatment of these patients, which may favour a lower incidence of post-operative complications. LEVEL OF EVIDENCE: Retrospective comparative study, Level IV.

Effect of intra-abdominal pressure on hepatic microcirculation: implications of the endothelin-1 receptor.

OBJECTIVE: To investigate the effect of endothelin receptor A (ET(A)) and endothelin receptor B (ET(B)) blockade on liver microcirculation and oxygenation during intra-abdominal pressure (IAP) increase. METHODS: Fifteen anesthetized pigs were randomized to receive either nonselective endothelin-1 (ET-1) blocker tezosentan (TG, n = 7) or saline (CG, n = 8). Helium was insufflated to increase IAP from 0 to 25 mmHg. Stroke volume variability was maintained ≤ 12% with colloid infusion. Total liver blood flow (TLBF), hepatic microcirculatory blood flow (MBF), hepatic tissue oxygenation (HpO(2)), hyaluronic acid and plasma disappearance rate (PDR) of indocyanine green (ICG) were recorded. RESULTS: TLBF remained mostly unaltered in both groups at low IAP and decreased only in CG at the IAP of 25 mmHg. As IAP increased, a significant decline in MBF was observed without correlation with cardiac output or TLBF. In CG, HpO(2) decreased as early as IAP of 10 mmHg to high levels of pressure. However, in TG the decrease was significant only at the IAP of 25 mmHg. PDR of ICG decreased in both groups at IAP of 25 mmHg (P = 0.046 and P = 0.009 in TG and CG, respectively). These changes correlated with MBF (r = 0.793). CONCLUSION: Blocking ET(A) and ET(B) receptors partially protects sinusoidal circulation and tissue oxygenation against stress induced by high IAP.

Teaching basic life support algorithms by either multimedia presentations or case based discussion equally improves the level of cognitive skills of undergraduate medical students.

BACKGROUND: There is no evidence on the best method for teaching Basic Life Support (BLS). AIMS: To compare two methods for teaching BLS, assessing the level of cognitive skills. METHODS: Randomized, prospective study including 68 medical students. BLS algorithms were taught for 60 minutes using either a multimedia presentation (Group I, n=34) or case based discussion (Group II, n=34). Assessments included a scenario-based quiz test and an error-pinpointing video, which the students completed before (T1) and after (T2) teaching. Comparisons between both groups were made on scores of the assessments, actual increases in scores (final value - initial value) and score gains (actual increase/potential increase). RESULTS: No significant differences were found between the groups in any of the recorded scores. Both groups improved their T2 scores (p values <0.001). The actual increases in scores and the score gains were similar in both groups. Test scores improved in 55.9% of students in Group I and 58.8% in Group II; video scores improved in 85.3% of Group I and in 82.3% of Group II. CONCLUSIONS: BLS teaching by either multimedia presentations or case based discussion equally improves the level of cognitive skills among medical students.

Hyperlactatemia in patients with non-acetaminophen-related acute liver failure.

AIM: To characterize hyperlactatemia in patients with non-acetaminophen acute liver failure (ALF) in an attempt to clarify the mechanisms implicated and the role as a prognosis factor. METHODS: In the setting of liver transplantation, 63 consecutive patients with non-acetaminophen acute liver failure were studied in relation to tissue oxygenation, hemodynamic and metabolic parameters. Before and after transplantation, the number of infected patients and outcome were registered. RESULTS: Acute ALF showed higher levels of lactate than subacute ALF (5.4+/- 1 mmol/L versus 2.2+/- 0.6 mmol/L, P=0.01). Oxygenation parameters were within the normal range. Lactate levels showed good correlation with respiratory quotient (r=0.759, P< 0.005), mean glucose administration (r=0.664, P=0.01) and encephalopathy (r=0.698, P=0.02), but not with splanchnic arteriovenous difference in PCO2, pH and the presence of infection (P=0.1). Portal vein lactate was higher (P< 0.05) than arterial and mixed venous lactate, suggesting its production of hyperlactatemia in the intestine and spleen. The presence of infection was an independent predictor of survival. CONCLUSION: Hyperlactatemia is not a prognosis factor due to byproduct of the overall acceleration in glycolysis.

Anesthetic management of a patient in prone position with a drill bit penetrating the spinal canal at C1-C2, using a laryngeal mask.

UNLABELLED: Airway management in patients with penetrating neck trauma must guarantee cervical spine stability. Moreover, the prone position increases the risk of difficult ventilation and cervical spine injury. A 19-yr-old patient was brought to the emergency room in prone position with a drill bit protruding from the posterolateral aspect of his neck. The bit had entered the spinal canal below the first cervical vertebra, and placed near the odontoid peg. He was referred for surgical removal of the drill. The use of an inhaled induction of anesthesia, avoiding muscle relaxants, and ventilation through a laryngeal mask airway inserted in the prone position seemed to offer a satisfactory approach. IMPLICATIONS: Management of patients with penetrating neck trauma must guarantee cervical spine stability. Moreover, the prone position increases the risk of difficult ventilation and cervical spine injury. Anesthesia may be induced and the airway can be managed with the patient already in the prone position for surgery.