Reference Ranges for Arterial Oxygen Saturation, Heart Rate, and Cerebral Oxygen Saturation during Immediate Postnatal Transition in Neonates Born Extremely or Very Preterm.

OBJECTIVE: To define percentile charts for arterial oxygen saturation (SpO2), heart rate (HR), and cerebral oxygen saturation (crSO2) during the first 15 minutes after birth in neonates born very or extremely preterm and with favorable outcome. STUDY DESIGN: We conducted a secondary-outcome analysis of neonates born preterm included in the Cerebral regional tissue Oxygen Saturation to Guide Oxygen Delivery in preterm neonates during immediate transition after birth III (COSGOD III) trial with visible cerebral oximetry measurements and with favorable outcome, defined as survival without cerebral injuries until term age. We excluded infants with inflammatory morbidities within the first week after birth. SpO2 was obtained by pulse oximetry, and electrocardiogram or pulse oximetry were used for measurement of HR. crSO2 was assessed with near-infrared spectroscopy. Measurements were performed during the first 15 minutes after birth. Percentile charts (10th to 90th centile) were defined for each minute. RESULTS: A total of 207 neonates born preterm with a gestational age of 29.7 (23.9-31.9) weeks and a birth weight of 1200 (378-2320) g were eligible for analyses. The 10th percentile of SpO2 at minute 2, 5, 10, and 15 was 32%, 52%, 83%, and 85%, respectively. The 10th percentile of HR at minute 2, 5, 10, and 15 was 70, 109, 126, and 134 beats/min, respectively. The 10th percentile of crSO2 at minute 2, 5, 20, and 15 was 15%, 27%, 59%, and 63%, respectively. CONCLUSIONS: This study provides new centile charts for SpO2, HR, and crSO2 for neonates born extremely or very preterm with favorable outcome. Implementing these centiles in guiding interventions during the stabilization process after birth might help to more accurately target oxygenation during postnatal transition period.

Von Willebrand Factor Antigen Improves Risk Stratification for Patients with a Diagnosis of Resectable Hepatocellular Carcinoma.

BACKGROUND: Posthepatectomy liver failure (PHLF), complications of portal hypertension, and disease recurrence determine the outcome for hepatocellular carcinoma (HCC) patients undergoing liver resection. This study aimed to evaluate the von Willebrand factor antigen (vWF-Ag) as a non-invasive test for clinically significant portal hypertension (CSPH) and a predictive biomarker for time to recurrence (TTR) and overall survival (OS). METHODS: The study recruited 72 HCC patients with detailed preoperative workup from a prospective trial (NCT02118545) and followed for complications, TTR, and OS. Additionally, 163 compensated patients with resectable HCC were recruited to evaluate vWF-Ag cutoffs for ruling out or ruling in CSPH. Finally, vWF-Ag cutoffs were prospectively evaluated in an external validation cohort of 34 HCC patients undergoing liver resection. RESULTS: In receiver operating characteristic (ROC) analyses, vWF-Ag (area under the curve [AUC], 0.828) was similarly predictive of PHLF as indocyanine green clearance (disappearance rate: AUC, 0.880; retention rate: AUC, 0.894), whereas computation of future liver remnant was inferior (AUC, 0.756). Cox-regression showed an association of vWF-Ag with TTR (per 10%: hazard ratio [HR], 1.056; 95% confidence interval [CI] 1.017-1.097) and OS (per 10%: HR, 1.067; 95% CI 1.022-1.113). In the analyses, VWF-Ag yielded an AUC of 0.824 for diagnosing CSPH, with a vWF-Ag of 182% or lower ruling out and higher than 291% ruling in CSPH. Therefore, a highest-risk group (> 291%, 9.7% of patients) with a 57.1% incidence of PHLF was identified, whereas no patient with a vWF-Ag of 182% or lower (52.7%) experienced PHLF. The predictive value of vWF-Ag for PHLF and OS was externally validated. CONCLUSION: For patients with resectable HCC, VWF-Ag allows for simplified preoperative risk stratification. Patients with vWF-Ag levels higher than 291% might be considered for alternative treatments, whereas vWF-Ag levels of 182% or lower identify patients best suited for surgery.

Neonatal somatic oxygenation and perfusion assessment using near-infrared spectroscopy : Part of the series on near-infrared spectroscopy by the European Society of Paediatric Research Special Interest Group "Near-Infrared Spectroscopy".

In this narrative review, we summarize the current knowledge and applications of somatic near-infrared spectroscopy (NIRS), with a focus on intestinal, renal, limb, and multi-site applications in neonates. Assessing somatic oxygenation at various body locations in neonates may aid in the understanding of underlying pathophysiology of organ injury. Considering cerebral autoregulation may be active to protect the brain during systemic circulatory failure, peripheral somatic oxygenation may potentially provide an early indication of neonatal cardiovascular failure and ultimate hypoxemic injury to vital organs including the brain. Certain intestinal oxygenation patterns appear to be associated with the onset and course of necrotizing enterocolitis, whereas impaired renal oxygenation may indicate the onset of acute kidney injury after various types of hypoxic events. Peripheral muscle oxygenation measured at a limb may be particularly effective in the early prediction of shock in neonates. Using multi-site NIRS may complement current approaches and clinical investigations to alert for neonatal tissue hypoxemia, and potentially even guide management. However, somatic NIRS has its inherent limitations in regard to accuracy. Interpretation of organ-specific values can also be challenging. Last, currently there are limited prospective intervention studies, and clinical benefits need to be examined further, after the clarification of critical threshold-values. IMPACT: The assessment of somatic oxygenation using NIRS may contribute to the prediction of specific diseases in hemodynamically challenged neonates. Furthermore, it may give early warning signs for impending cardiovascular failure, and impaired cerebral circulation and oxygenation. We present a comprehensive overview of the literature on applications of NIRS to various somatic areas, with a focus on its potential clinical applicability, including future research directions. This paper will enable prospective standardized studies, and multicenter collaboration to obtain statistical power, likely to advance the field.

A recommendation for the use of electrical biosensing technology in neonatology.

Non-invasive cardiac output monitoring, via electrical biosensing technology (EBT), provides continuous, multi-parameter hemodynamic variable monitoring which may allow for timely identification of hemodynamic instability in some neonates, providing an opportunity for early intervention that may improve neonatal outcomes. EBT encompasses thoracic (TEBT) and whole body (WBEBT) methods. Despite the lack of relative accuracy of these technologies, as compared to transthoracic echocardiography, the use of these technologies in neonatology, both in the research and clinical arena, have increased dramatically over the last 30 years. The European Society of Pediatric Research Special Interest Group in Non-Invasive Cardiac Output Monitoring, a group of experienced neonatologists in the field of EBT, deemed it appropriate to provide recommendations for the use of TEBT and WBEBT in the field of neonatology. Although TEBT is not an accurate determinant of cardiac output or stroke volume, it may be useful for monitoring longitudinal changes of hemodynamic parameters. Few recommendations can be made for the use of TEBT in common neonatal clinical conditions. It is recommended not to use WBEBT to monitor cardiac output. The differences in technologies, study methodologies and data reporting should be addressed in ongoing research prior to introducing EBT into routine practice. IMPACT STATEMENT: TEBT is not recommended as an accurate determinant of cardiac output (CO) (or stroke volume (SV)). TEBT may be useful for monitoring longitudinal changes from baseline of hemodynamic parameters on an individual patient basis. TEBT-derived thoracic fluid content (TFC) longitudinal changes from baseline may be useful in monitoring progress in respiratory disorders and circulatory conditions affecting intrathoracic fluid volume. Currently there is insufficient evidence to make any recommendations regarding the use of WBEBT for CO monitoring in neonates. Further research is required in all areas prior to the implementation of these monitors into routine clinical practice.

Nephrolithiasis Associated with Nephrocalcinosis Is Primarily Composed of Carbonate Apatite.

INTRODUCTION: This study was designed to determine the mineral composition of calculi in nephrocalcinosis with nephrolithiasis, diagnose the underlying disease, and monitor the course of renal function in patients with nephrocalcinosis-nephrolithiasis. METHODS: Renal calculi extruded in a series of 8 patients with nephrocalcinosis were analysed using Fourier transmission infrared spectrometry. In 4 patients, next-generation sequencing using a nephrocalcinosis-nephrolithiasis panel was performed to determine the nature of the underlying disease. In addition, longitudinal analysis of renal function was performed in all patients. RESULTS: Seven patients revealed carbonate apatite as the sole constituent of renal calculi. One patient showed a mixed composition of dicalcium phosphate dihydrate/carbonate apatite at first analysis yet in subsequent episodes also had calculi composed of pure carbonate apatite. Further molecular analysis displayed distal renal tubular acidosis in 2 of 4 patients who consented to sequencing. No known genetic defect could be found in the other two cases. In line with prior reports, decline of renal function was dependent on underlying disease. Distal renal tubular acidosis revealed a progressive course of renal failure, whereas other causes showed stable renal function in long term analysis. CONCLUSION: Nephrocalcinosis with nephrolithiasis is a rare condition with heterogeneous aetiology. Yet mineral composition of renal calculi predominantly consisted of pure carbonate apatite. This uniform finding is similar to subcutaneous calcifications of various origins and might propose a general principle of tissue calcification. Progressive decline of renal function was found in distal renal tubular acidosis, whereas other conditions remained stable over time.

Pulse oximetry signal loss during hypoxic episodes in preterm infants receiving automated oxygen control.

The aim of this study was to analyze signal loss (SL) resulting from low signal quality of pulse oximetry-derived hemoglobin oxygen saturation (SpO2) measurements during prolonged hypoxemic episodes (pHE) in very preterm infants receiving automatic oxygen control (AOC). We did a post hoc analysis of a randomized crossover study of AOC, programmed to set FiO2 to "back-up FiO2" during SL. In 24 preterm infants (median (interquartile range)) gestational age 25.3 (24.6 to 25.6) weeks, recording time 12.7 h (12.2 to 13.6 h) per infant, we identified 76 pHEs (median duration 119 s (86 to 180 s)). In 50 (66%) pHEs, SL occurred for a median duration of 51 s (33 to 85 s) and at a median frequency of 2 (1 to 2) SL-periods per pHE. SpO2 before and after SL was similar (82% (76 to 88%) vs 82% (76 to 87%), p = 0.3)).  Conclusion: SL is common during pHE and must hence be considered in AOC-algorithm designs. Administering a "backup FiO2" (which reflects FiO2-requirements during normoxemia) during SL may prolong pHE with SL.  Trial registration: The study was registered at www. CLINICALTRIALS: gov under the registration no. NCT03785899. WHAT IS KNOWN: • Previous studies examined SpO2 signal loss (SL) during routine manual oxygen control being rare, but pronounced in lower SpO2 states. • Oxygen titration during SL is unlikely to be beneficial as SpO2 may recover to a normoxic range. WHAT IS NEW: • Periods of low signal quality of SpO2 are common during pHEs and while supported with automated oxygen control (SPOC), FiO2 is set to a back-up value reflecting FiO2 requirements during normoxemia in response to SL, although SpO2 remained below target until signal recovery. • FiO2 overshoots following pHEs were rare during AOC and occurred with a delayed onset; therefore, increased FiO2 during SL does not necessarily lead to overshoots.

Facial growth dynamics dictate optimal facemask fitting during the first year of life.

AIM: The aim of this study is to prevent mask leak during ventilation in infant emergencies, appropriate facemask fitting is essential. Therefore, we investigated facial profiles during the first year of life and their correlation with the correct sizing of masks. METHODS: This is a post hoc subgroup analysis of 32 healthy term infants, based on a prospective observational study performed from September 2018 to December 2019 in Tuebingen, Germany. In 3-monthly intervals, facial aspects were measured based on anatomical landmarks in three-dimensional frontal photographs to describe their changes across the first year of life. All infants were awake and breathing spontaneously; none required any anaesthesia. RESULTS: In 130 3D images, mean distance between nasion and gnathion was 54 mm (3.3) measured at birth and 70 mm (3.5) at age 12 months. Gompertz models showed relevant growth-related changes in the facial profile in vertical but not horizontal direction. Vertical growth occurred mainly in the first 6 months. Boys and girls differed by an average of about 2 mm (boys >girls). CONCLUSION: Based on our findings, it should now be verified whether the 50 mm facemasks are suitable for infants from birth to 2 months of age, respectively, the 60 mm version for infants aged three to 12 months.

E-AHPBA-ESSO-ESSR Innsbruck consensus guidelines for preoperative liver function assessment before hepatectomy.

BACKGROUND: Posthepatectomy liver failure (PHLF) contributes significantly to morbidity and mortality after liver surgery. Standardized assessment of preoperative liver function is crucial to identify patients at risk. These European consensus guidelines provide guidance for preoperative patient assessment. METHODS: A modified Delphi approach was used to achieve consensus. The expert panel consisted of hepatobiliary surgeons, radiologists, nuclear medicine specialists, and hepatologists. The guideline process was supervised by a methodologist and reviewed by a patient representative. A systematic literature search was performed in PubMed/MEDLINE, the Cochrane library, and the WHO International Clinical Trials Registry. Evidence assessment and statement development followed Scottish Intercollegiate Guidelines Network methodology. RESULTS: Based on 271 publications covering 4 key areas, 21 statements (at least 85 per cent agreement) were produced (median level of evidence 2- to 2+). Only a few systematic reviews (2++) and one RCT (1+) were identified. Preoperative liver function assessment should be considered before complex resections, and in patients with suspected or known underlying liver disease, or chemotherapy-associated or drug-induced liver injury. Clinical assessment and blood-based scores reflecting liver function or portal hypertension (for example albumin/bilirubin, platelet count) aid in identifying risk of PHLF. Volumetry of the future liver remnant represents the foundation for assessment, and can be combined with indocyanine green clearance or LiMAx® according to local expertise and availability. Functional MRI and liver scintigraphy are alternatives, combining FLR volume and function in one examination. CONCLUSION: These guidelines reflect established methods to assess preoperative liver function and PHLF risk, and have uncovered evidence gaps of interest for future research.

Liver surgery is an effective treatment for liver tumours. Liver failure is a major problem in patients with a poor liver quality or having large operations. The treatment options for liver failure are limited, with high death rates. To estimate patient risk, assessing liver function before surgery is important. Many methods exist for this purpose, including functional, blood, and imaging tests. This guideline summarizes the available literature and expert opinions, and aids clinicians in planning safe liver surgery.

Gas in scattering media absorption spectroscopy as a potential tool in neonatal respiratory care.

Gas in scattering media absorption spectroscopy (GASMAS) is a novel optical technology employing near-infrared light. It has a potential use in the medical setting as a monitoring and diagnostic tool by detecting molecular oxygen within gas pockets and thus may be a useful adjunct in respiratory monitoring. GASMAS has potential advantages over other monitoring devices currently used in clinical practice. It is a non-invasive, continuous, non-ionising technology and provides unique information about molecular oxygen content inside the lungs. GASMAS may have a future role in optimising respiratory management of neonates in different clinical scenarios such as monitoring cardiorespiratory transition in the delivery room, assessing surfactant deficiency, and optimising endotracheal tube positioning. This article aims to summarise current evidence exploring GASMAS application in a neonate, discuss possible clinical benefits, and compare with other devices that are currently used in neonatal care. IMPACT: This article presents a novel optical technique to measure lung oxygen concentrations that may have important clinical uses. This review summarises the current literature investigating the concept of optical lung oxygen measurement. Information from this review can guide researchers in future studies.

Hyponatremia in the emergency department.

Hyponatremia, defined as a serum sodium <135 mmol/L, is frequently encountered in patients presenting to the emergency department. Symptoms are often unspecific and include a recent history of falls, weakness and vertigo. Common causes of hyponatremia include diuretics, heart failure as well as Syndrome of Inappropriate Antidiuresis (SIAD) and correct diagnosis can be challenging. Emergency treatment of hyponatremia should be guided by presence of symptoms and focus on distinguishing between acute and chronic hyponatremia.

Immune checkpoints and liver resection after neoadjuvant chemotherapy including bevacizumab in patients with microsatellite-stable colorectal liver metastases.

BACKGROUND: The clinical value of immune checkpoint expression as prognostic biomarker in bevacizumab-pretreated patients with resected microsatellite-stable (MMS) colorectal liver metastases is unclear and was retrospectively investigated in this study. METHODS: Expression analyses of IDO-1, PD-L1, and CTLA-4 were performed by immunohistochemistry in resected bevacizumab-pretreated colorectal liver metastases. Association of immune checkpoint expression in tumor cells and immune cells with response and clinical outcome was investigated. Expression profiles were compared with those of patients with anti-EGFR-targeted therapy and lung metastases, respectively. RESULTS: One hundred thirty-six patients with MMS disease were investigated (79 (58.1%) male/57 (41.9%) female, median age 62.9 years (range 31.0-80.4)). High expression of IDO-1 in immune cells was associated with longer OS (not reached versus 44.8 months, HR 0.23 (95% CI 0.09, 0.55), P = 0.001). Low expression of CTLA-4 in tumor cells was associated with better histological response (26 major, 19 partial, 18 none versus 14 major, 23 partial, 30 none, P = 0.032). Expression profiles differed compared to patients with anti-EGFR-targeted therapy and patients with lung metastases. CONCLUSION: Immune checkpoint expression was associated with response and survival. IDO-1 may serve as a novel prognostic and/or predictive biomarker in patients with MMS colorectal liver metastases.

In vivo Treg expansion under costimulation blockade targets early rejection and improves long-term outcome.

CTLA4Ig has been shown to improve kidney allograft function, but an increased frequency of early rejection episodes poses a major obstacle for more widespread clinical use. The deleterious effect of CTLA4Ig on Treg numbers provides a possible explanation for graft injury. Therefore, we aimed at improving CTLA4Ig's efficacy by therapeutically increasing the number of Tregs. Murine cardiac allograft transplantation (BALB/c  to B6) was performed under CTLA4Ig therapy modeled after the clinically approved dosing regimen and Tregs were transferred early or late after transplant. Neither early nor late Treg transfer prolonged allograft survival. Transferred Tregs were traceable in various lymphoid compartments but only modestly increased overall Treg numbers. Next, we augmented Treg numbers in vivo by means of IL2 complexes. A short course of IL2/anti-IL2-complexes administered before transplantation reversed the CTLA4Ig-mediated decline in Tregs. Of note, the addition of IL2/anti-IL2-complexes to CTLA4Ig therapy substantially prolonged heart allograft survival and significantly improved graft histology on day 100. The depletion of Tregs abrogated this effect and resulted in a significantly diminished allograft survival. The increase in Treg numbers upon IL2 treatment was associated with a decreased expression of B7 on dendritic cells. These results demonstrate that therapy with IL2 complexes improves the efficacy of CTLA4Ig by counterbalancing its unfavorable effect on Tregs.

Prognosis and Circumferential Margin in Patients with Resected Hilar Cholangiocarcinoma.

BACKGROUND: Resection margin status is a known prognosticator in patients who undergo resection for hilar cholangiocarcinoma. However, the influence of an isolated positive circumferential margin on clinical outcome is unclear. METHODS: Patients with resected de novo hilar cholangiocarcinoma from two European hepatobiliary centres (Medical University of Vienna and Aintree University Hospital, 2006-2016) were classified according to resection margin status (negative, surgically positive, isolated circumferentially positive) and investigated with respect to overall survival (OS), recurrence-free survival (RFS) and recurrence pattern. RESULTS: Eighty-three (48 male/35 female) patients were enrolled. The median age was 64 years (range 33-80). The median follow-up was 21.7 months (range 0.3-92.4). Forty (48%) patients had negative resection margins, 25 (30%) had an isolated positive circumferential margin and 18 (22%) had a positive surgical margin. The 5-year OS rates in patients with negative, isolated positive circumferential and positive surgical resection margins were 47%, 33% and 0%, respectively. Median OS was 45.6, 32.7 and 14.5 months, respectively (log rank, P = 0.011). Upon multivariable Cox regression analysis, resection margin status and lymph node status remained statistically significant (P < 0.05). No difference with respect to RFS and recurrence pattern was found between the groups (P > 0.05). CONCLUSION: Our data show that these three resection margin types were associated with different clinical outcomes. Circumferential margin status may therefore serve as a novel prognostic biomarker.

Near-infrared spectroscopy for perioperative assessment and neonatal interventions.

Perioperative applications of near-infrared spectroscopy (NIRS) to monitor regional tissue oxygenation and perfusion in cardiac and noncardiac surgery are of increasing interest in neonatal care. Complex neonatal surgery can impair adequate oxygen delivery and tissue oxygen consumption and increase the risk of neurodevelopmental delay. Coupled with conventional techniques, NIRS monitoring may enable targeted hemodynamic management of the circulation in both cardiac and noncardiac surgical procedures. In this narrative review, we discuss the application of perioperative NIRS in specific neonatal interventions, including surgical intervention for congenital heart defects, definitive closure of the patent ductus arteriosus, neurological and gastrointestinal disorders, and use of extracorporeal membrane oxygenation. We identified areas for future research within disease-specific indications and offer a roadmap to aid in developing evidence-based targeted diagnostic and management strategies in neonates. IMPACT: There is growing recognition that perioperative NIRS monitoring, used in conjunction with conventional monitoring, may provide critical hemodynamic information that either complements clinical impressions or delivers novel physiologic insight into the neonatal circulatory and perfusion pathways.

Dyskalemias in patients with acute kidney injury presenting to the emergency department are common and independent predictors of adverse outcome.

BACKGROUND: No data concerning the prevalence and risk factors of dyskalemia in acute kidney injury (AKI) exist. We investigated (a) prevalence rates, (b) risk factors and (c) outcome of hypo- and hyperkalemia in emergency patients. METHODS: In this cross-sectional analysis, all patients admitted to the emergency department of a large public hospital in Switzerland between January 1st 2017 and December 31st 2018 with measurements of creatinine and potassium were included. Baseline characteristics, medication and laboratory data were extracted. Chart reviews were performed to identify patients with a diagnosis of chronic kidney disease (CKD) and to extract their baseline creatinine. For all other patients, the ADQI backformula was used in order to calculate baseline creatinine. AKI was graduated using creatinine criteria of the acute kidney injury network. Binary logistic regression analysis was used to identify risk factors for appearance of hyperkalemia and outcome. RESULTS: AKI was found in 8% of patients. Hyperkalemia was present in 13% and hypokalemia in 11% of patients with AKI. AKI stage, potassium-sparing diuretics, ACE inhibitors and underlying CKD were the strongest risk factors for hyperkalemia. Hyperkalemia as well as profound hypokalemia were independently associated with prolonged length of stay and in-hospital mortality. The study is limited by its dependency on chart review data in order to identify patients with chronic kidney disease and by limitations of the ADQI backformula to calculate baseline creatinine. CONCLUSIONS: Dyskalemias are common in emergency patients with AKI and are independent risk factors for adverse outcomes. Potassium-sparing diuretics, ACE-inhibitors, AKIN stage and CKD are predictors of hyperkalemia in AKI.

Dysnatremias in emergency patients with acute kidney injury: A cross-sectional analysis.

PURPOSE: We aimed to investigate the prevalence, risk factors and outcome of hypo- and hypernatremia in emergency patients with acute kidney injury (AKI). METHODS: In this cross-sectional analysis all emergency patients between January 1st 2017 and December 31st 2018 with measurements of creatinine and sodium were included. Baseline characteristics, medication and laboratory data were gathered. Chart reviews were performed to identify patients with a diagnosis of chronic kidney disease (CKD) and to extract baseline creatinine. For all other patients the ADQI backformula was used to calculate baseline creatinine. AKI was graduated using creatinine criteria of the acute kidney injury network. Binary logistic regression analysis was used to identify risk factors for appearance of dysnatremias and outcome. RESULTS: AKI was found in 8% of patients. 392 patients (23.16%) had hyponatremia, 24 (1.4%) had hypernatremia. Use of potassium sparing diuretics, a medical cause for emergency referral, use of thiazide diuretics and AKI stage were the strongest risk factors for hyponatremia. Loop diuretics, a medical cause for emergency referral and AKI stage were risk factors for hypernatremia. In patients with all classes of hyponatremia, length of hospital stay was significantly longer compared to patients with a normal serum sodium. In the binary logistic regression analysis with death as outcome, hyponatremia as well as severe hypernatremia were independent risk factors for mortality. CONCLUSIONS: Dysnatremias are common in emergency patients with AKI. Diuretic medication is a major risk factor for hypo- and hypernatremia. Both hyponatremia and severe hypernatremia were independent risk factors for adverse outcome.

Allograft rejection is associated with development of functional IgE specific for donor MHC antigens.

BACKGROUND: Donor-specific antibodies of the IgG isotype are measured routinely for diagnostic purposes in renal transplant recipients and are associated with antibody-mediated rejection and long-term graft loss. OBJECTIVE: This study aimed to investigate whether MHC-specific antibodies of the IgE isotype are induced during allograft rejection. METHODS: Anti-MHC/HLA IgE levels were measured in sera of mice grafted with skin or heart transplants from various donor strains and in sera of kidney transplant patients with high levels of HLA IgG. Mediator release was triggered in vitro by stimulating basophils that were coated with murine or human IgE-positive serum, respectively, with specific recombinant MHC/HLA antigens. Kidney tissue samples obtained from organ donors were analyzed by using flow cytometry for cells expressing the high-affinity receptor for IgE (FcεRI). RESULTS: Donor MHC class I- and MHC class II-specific IgE was found on acute rejection of skin and heart grafts in several murine strain combinations, as well as during chronic antibody-mediated heart graft rejection. Anti-HLA IgE, including donor HLA class I and II specificities, was identified in a group of sensitized transplant recipients. Murine and human anti-MHC/HLA IgE triggered mediator release in coated basophils on stimulation with specific MHC/HLA antigens. HLA-specific IgE was not linked to atopy, and allergen-specific IgE present in allergic patients did not cross-react with HLA antigens. FcεRI+ cells were found in the human renal cortex and medulla and provide targets for HLA-specific IgE. CONCLUSION: These results demonstrate that MHC/HLA-specific IgE develops during an alloresponse and is functional in mediating effector mechanisms.

Allograft and patient survival after sequential HSCT and kidney transplantation from the same donor-A multicenter analysis.

Tolerance induction through simultaneous hematopoietic stem cell and renal transplantation has shown promising results, but it is hampered by the toxicity of preconditioning therapies and graft-versus-host disease (GVHD). Moreover, renal function has never been compared to conventionally transplanted patients, thus, whether donor-specific tolerance results in improved outcomes remains unanswered. We collected follow-up data of published cases of renal transplantations after hematopoietic stem cell transplantation from the same donor and compared patient and transplant kidney survival as well as function with caliper-matched living-donor renal transplantations from the Austrian dialysis and transplant registry. Overall, 22 tolerant and 20 control patients were included (median observation period 10 years [range 11 months to 26 years]). In the tolerant group, no renal allograft loss was reported, whereas 3 were lost in the control group. Median creatinine levels were 85 µmol/l (interquartile range [IQR] 72-99) in the tolerant cohort and 118 µmol/l (IQR 99-143) in the control group. Mixed linear-model showed around 29% lower average creatinine levels throughout follow-up in the tolerant group (P < .01). Our data clearly show stable renal graft function without long-term immunosuppression for many years, suggesting permanent donor-specific tolerance. Thus sequential transplantation might be an alternative approach for future studies targeting tolerance induction in renal allograft recipients.

Application of NPE in the assessment of a patent ductus arteriosus.

In many preterm infants, the ductus arteriosus remains patent beyond the first few days of life. This prolonged patency is associated with numerous adverse outcomes, but the extent to which these adverse outcomes are attributable to the hemodynamic consequences of ductal patency, if at all, has not been established. Different treatment strategies have failed to improve short-term outcomes, with a paucity of data on the correct diagnostic and pathophysiological assessment of the patent ductus arteriosus (PDA) in association with long-term outcomes. Echocardiography is the selected method of choice for detecting a PDA, assessing the impact on the preterm circulation and monitoring treatment response. PDA in a preterm infant can result in pulmonary overcirculation and systemic hypoperfusion, Therefore, echocardiographic assessment should include evaluation of PDA characteristics, indices of pulmonary overcirculation with left heart loading conditions, and indices of systemic hypoperfusion. In this review, we provide an evidence-based overview of the current and emerging ultrasound measurements available to identify and monitor a PDA in the preterm infant. We offer indications and limitations for using Neonatologist Performed Echocardiography to optimize the management of a neonate with a PDA.