Are Buffy-coat Pooled Platelet Concentrates an Effective Alternative to Apheresis Platelet Concentrates? An In vitro Analysis at a Tertiary Care Center in Northern India.

Background: There is a need for platelet products to have the best quality. Apheresis platelet concentrates (PCs) obtained from single-donors PCs (SD-PCs) are considered best but have issues such as feasibility and cost. Buffy-coat pooled PCs (BCP-PCs) are considered an alternative to SD-PCs. This study compares BCP-PCs and SD-PCs for in vitro quality parameters and their changes during storage. Materials and Methods: Fifteen units of BCP-PCs and 15 units of SD-PCs were prepared. In this study, a pool of five buffy coats was prepared. Fifteen units of BCP-PCs were analyzed on day 1 and day 5 of storage, while 15 SD-PCs were analyzed on day 1 while ten units on day 5. The parameters analyzed were volume, hematological parameters, pH, swirling, and sterility. Results: The mean platelets count of SD-PCs was found to be significantly higher as compared to BCP-PCs. White blood cells (WBCs) contamination was significantly lower in BCP-PCs as compared to SD-PCs. The mean pH and mean platelet volume of SD-PCs were significantly lower than BCP-PCs. During storage, the mean platelets count of BCP-PCs was decreased significantly while that of SD-PCs nonsignificantly. The mean WBCs count and pH decreased in both BCP-PCs and SD-PCs significantly. All units in both types of PCs were sterile. Conclusion: Platelet yield was significantly better in SD-PCs, while mean WBCs contamination was significantly lower in BCP-PCs. BCP-PCs may be preferred in place of SD-PCs in case of nonavailability of apheresis, difficulty in finding a willing donor, or when the cost is of consideration.

Does Severity of Brain Injury on Magnetic Resonance Imaging Predict Short-Term Outcome in Neonates Who Received Therapeutic Hypothermia?

OBJECTIVE: The National Institute of Child Health and Human Development (NICHD) magnetic resonance imaging (MRI) pattern of brain injury is a known biomarker of childhood outcome following therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE). However, usefulness of this classification has not been evaluated to predict short-term outcomes. The study aimed to test the hypothesis that infants with NICHD MRI pattern of severe hypoxic-ischemic brain injury will be sicker with more severe asphyxia-induced multiorgan dysfunction resulting in prolonged length of stay (LOS) following therapeutic hypothermia. We also evaluated the role of other risk factors which may prolong LOS. STUDY DESIGN: We retrospectively reviewed the medical records of 71 consecutively cooled neonates to examine the ability of MRI patterns of brain injury to predict the LOS. A neuroradiologist masked to outcomes classified the patterns of brain injury on MRI as per NICHD. Pattern 2A (basal ganglia thalamic, internal capsule, or watershed infarction), 2B (2A with cerebral lesions), and 3 (hemispheric devastation) of brain injury was deemed "severe injury." RESULTS: Out of 71 infants, 59 surviving infants had both MRI and LOS data. LOS was higher for infants who had Apgar's score of ≤5 at 10 minutes, severe HIE, seizures, coagulopathy, or needed vasopressors or inhaled nitric oxide, or had persistent feeding difficulty, or remained intubated following cooling. However, median LOS did not differ between the infants with and without MRI pattern of severe injury (15 days, interquartile range [IQR]: 9-28 vs. 12 days, IQR: 10-20; p = 0.4294). On multivariate linear regression analysis, only persistent feeding difficulty (ß coefficient = 11, p = 0.001; or LOS = 11 days longer if had feeding difficulty) and ventilator days (ß coefficient 1.7, p < 0.001; or LOS increased 1.7 times for each day of ventilator support) but not the severity of brain injury predicted LOS. CONCLUSION: Unlike neurodevelopmental outcome, LOS is not related to severity of brain injury as defined by the NICHD. KEY POINTS: · The NICHD pattern of brain injury on MRI predicts neurodevelopmental outcome following hypothermia treatment for neonatal HIE.. · LOS did not differ between the infants with and without MRI patterns of severe injury.. · The severity of brain injury as defined by the NICHD was not predictive of the LOS following therapeutic hypothermia..

Trends in small molecule drug properties: A developability molecule assessment perspective.

Developability molecule assessment is a key interfacial capability across the biopharmaceutical industry, screening and staging molecules discovered by medicinal chemists for successful chemistry manufacturing controls (CMC) development and launch. The breadth of responsibility and expertise such teams possess puts them in a unique position to understand the impact of the physicochemical properties of a drug during its initial discovery and subsequent development. However, most of the publications describing trends in physicochemical properties are written from a medicinal chemistry perspective with the aim to identify molecules with better ADMET profiles that are either lead-like or drug-like, failing to describe the impact these properties have on CMC development. To systematically uncover knowledge obtained from recent trends in physicochemical properties and the corresponding impact on CMC development, a comprehensive analysis was conducted on molecules in the drug repurposing hub dataset. The only physicochemical property that seems to have been preserved in FDA-approved oral molecules over the decades (1900-2020) is a constant H-bond donor count, highlighting the importance this property has on cell permeability and lattice energy. Pharmaceutical attrition analysis suggests that partition-distribution coefficient, H-bond acceptors, polar surface area and the fraction of sp3 carbons are properties that are associated with compound attrition. Looking at pharmaceutical attrition asynchronously with the temporal analysis of FDA-approved oral molecules highlights the opposing trends, risks and diminishing effects some of these physiochemical properties (cLogP, cLogD and Fsp3) have on describing compound attrition during the past decade. Trellising the dataset by target class suggests that certain formulation and drug delivery strategies can be anticipated or put into place based on target class of a molecule. For example, molecules binding to nuclear hormone receptors are amenable to lipid-based drug delivery systems with proven commercial success. Although the poor solubility of kinase inhibitors is a combination of hydrophobicity (due to aromaticity) required to bind to its target and high lattice energy (melting point), they are a challenging target class to formulate. The influence of drug targets on physicochemical properties and the temporal nature of these properties is highlighted when comparing molecules in the drug repurposing dataset to those developed at Amgen. An improved understanding of the impact of molecular properties on performance attributes can accelerate decisions and facilitate risk assessments during candidate selection and development.

Postdischarge Adverse Events Among Neonates Admitted to the Neonatal Intensive Care Unit.

OBJECTIVES: We aimed to determine the rate of postdischarge adverse events (AEs), classify the types of postdischarge AEs, and identify risk factors for postdischarge AEs among neonates admitted to the neonatal intensive care unit (NICU). STUDY DESIGN: This was a prospective cohort study of neonates admitted to the NICU from February 2017 through June 2019. We enrolled 170 neonates from a level 4 NICU who were being discharged home and whose parents can speak English and could be contacted after discharge. The main outcome of the study was postdischarge AEs based on structured telephone interviews, health record review, and adjudication by 2 blinded, trained physicians using a previously established methodology. RESULTS: Fourteen percent of 170 neonates admitted to the NICU experienced postdischarge AEs, with 48% being either preventable or ameliorable. Adverse drug events and procedural complications comprised most of the AEs (48%), but most of the preventable and ameliorable AEs were due to management, therapeutic, or diagnostic errors. Seventy-nine percent of neonates who suffered an AE experienced either a readmission to the hospital or an emergency department visit. Neonates admitted to a level 4 NICU from another NICU (level 1, 2, or 3) (adjusted odds ratio, 3.62; 95% confidence interval, 1.27-12.60; P = 0.01) and those 28 to 36 weeks (adjusted odds ratio, 11.38; 95% confidence interval, 1.67-127.98; P = 0.01) had a significantly higher risk of AEs at discharge. CONCLUSIONS: Neonates discharged from a level 4 NICU were at high risk for experiencing postdischarge AEs. The identification of AE types and risk factors can be used to guide efforts to develop interventions to improve neonatal patient safety during the postdischarge period.

Echocardiographic measures of ventricular-vascular interactions in congenital diaphragmatic hernia.

OBJECTIVE: To evaluate the utility of echocardiographic measures of ventricular-vascular interactions in predicting death or ECMO in congenital diaphragmatic hernia (CDH). DESIGN: In this single center retrospective study, early (<48 hour age) Doppler ECHOs of neonates (≥34 weeks gestation) with CDH (n = 58) were reviewed. ECHO measures of the relationship of right ventricular (RV) contractility and pulmonary hypertension (PH) were selected: Ratios of 1. pulmonary artery acceleration time to pulmonary ejection time (PAAT/PET) 2. tricuspid annular plane systolic excursion, a measure of regional RV function, to PAAT (TAPSE/PAAT) 3. patent ductus arteriosus (PDA) flow velocity time integral (VTI) from right to left (PDA/RLVTI) 4. PDA flow duration from right to left (PDA/RL) and 5. TAPSE to RV systolic pressure (TAPSE/RVSP). Statistical analyses included t-test and chi-square test and receiver operating characteristic curves were generated. RESULTS: Our cohort (n = 58) comprised 34 (59%) males and predominantly (81%) left sided CDH. Of these, 34 (58.6%) infants died or received ECMO and 24 (41.4%) survived without ECMO. RVSP and PDA/RL VTI were higher, and RV TAPSE, PAAT/PET, TAPSE/PAAT and TAPSE/RVSP ratios were all significantly lower in the death/ECMO group. PDA/RLVTI ratio had the highest area under the curve (0.76); values ≥ 0.6 had high specificity [88% (95% C.I. 62-98%)] and positive predictive value [88% (95% C.I. 65-96%)] for adverse outcomes. CONCLUSION(S): Novel early ECHO parameters which combine RV function and PH severity were found to be feasible and prognostic in CDH. A detailed non-invasive assessment of ventricular-vascular interactions is important for risk-stratification in this population.

Venovenous versus venoarterial extracorporeal membrane oxygenation among infants with hypoxic-ischemic encephalopathy: is there a difference in outcome?

OBJECTIVE: Our hypothesis was that among infants with hypoxic-ischemic encephalopathy (HIE), venoarterial (VA), compared to venovenous (VV), extracorporeal membrane oxygenation (ECMO) is associated with an increased risk of mortality or intracranial hemorrhage (ICH). DESIGN/METHODS: Retrospective cohort analysis of infants in the Children's Hospitals Neonatal Database from 2010 to 2016 with moderate or severe HIE, gestational age ≥36 weeks, and ECMO initiation <7 days of age. The primary outcome was mortality or ICH. RESULTS: Severe HIE was more common in the VA ECMO group (n = 57), compared to the VV ECMO group (n = 53) (47.4% vs. 26.4%, P = 0.02). VA ECMO was associated with a significantly higher risk of death or ICH [57.9% vs. 34.0%, aOR 2.39 (1.08-5.28)] and mortality [31.6% vs. 11.3%, aOR 3.06 (1.08-8.68)], after adjusting for HIE severity. CONCLUSIONS: In HIE, VA ECMO was associated with a higher incidence of mortality or ICH. VV ECMO may be beneficial in this population.

Comparison of 5% human albumin and normal saline for fluid resuscitation in sepsis induced hypotension among patients with cirrhosis (FRISC study): a randomized controlled trial.

AIMS: Sepsis and septic shock are common causes of hospitalization and mortality in patients with cirrhosis. There is no data on the choice of fluid and resuscitation protocols in sepsis-induced hypotension in cirrhosis. METHODS: In this open-label trial conducted at a single center, we enrolled 308 cirrhotics with sepsis-induced hypotension and randomized them to receive either 5% albumin or normal saline. The primary endpoint was a reversal of hypotension [mean arterial pressure, MAP, ≥ 65 mmHg] at 3 h. Secondary endpoints included serial effects on heart rate, arterial lactate and urine output. RESULTS: 154 patients each received 5% albumin (males, 79.8%, mean MAP 52.9 ± 7.0 mm Hg) or 0.9% saline (85.1%, 53.4 ± 6.3 mm Hg) with comparable baseline parameters and liver disease severity. Reversal of hypotension was higher in patients receiving 5% albumin than saline at the end of one hour [25.3% and 11.7%, p = 0.03, Odds ratio (95% CI)-1.9 (1.08-3.42)] and at the end of three hours [11.7% and 3.2%, p = 0.008, 3.9 (1.42-10.9)]. Sustained reduction in heart rate and hyperlactatemia (p < 0.001) was better in the albumin group. At one week, the proportion of patients surviving was higher in the albumin group than those receiving saline (43.5% vs 38.3%, p = 0.03). Female gender and SOFA ≥ 11 were predictors of non-response to fluid. CONCLUSIONS: 5% human albumin is safe and beneficial in reversing sepsis-induced hypotension compared to normal saline in patients with cirrhosis improving clinically assessable parameters of systemic hemodynamics, tissue perfusion and in-hospital short-term survival of cirrhosis patients with sepsis.

Latent fingerprint development by using silver nanoparticles and silver nitrate-A comparative study.

The beginning of latent fingerprint development on porous surface was first achieved by silver nitrate (AgNO3 ) method. But the significantly increasing cost has caused forensic experts to look for an alternative means. Silver nitrate (AgNO3 ) is the main component in the synthesis of metal nanoparticles, namely silver nanoparticles (AgNPs). Owing to its unique property to adhere with fingerprint residue, AgNPs have attracted a great attention in the domain of nano-forensic fingerprinting. This study mainly focuses on the use of lower concentration of silver nitrate through new AgNP development method. The AgNPs were synthesized by wet chemical method with different molar concentrations (0.1, 0.01, and 0.001 M) of silver nitrate, characterized by ultraviolet visible spectrophotometer and high-resolution transmission electron microscope (HR-TEM). The average diameter of AgNPs calculated by HR-TEM was 10.66 ± 1.22 nm at 0.1 M, 12.50 ± 2.64 nm at 0.01 M, and 14.44 ± 2.68 nm at 0.001 M, respectively. A comparative analysis was also carried out to see the quality and stability of fingerprints produced on paper or porous substrate by using AgNO3 and AgNPs, respectively. During the study, AgNPs were able to develop distinct ridge details and were found to be stable for more than a month. Comparatively, when AgNO3 was used as the developing agent for the latent fingerprints, only faint ridge patterns were observed which further showed degradation of fingerprint stability within about 20 days. Overall, the current AgNP method showed good visibility and stability by using lower concentration of silver nitrate which can be used in place of conventional AgNO3 method.

Outcomes of infants with hypoxic ischemic encephalopathy and persistent pulmonary hypertension of the newborn: results from three NICHD studies.

OBJECTIVE: To determine the association of persistent pulmonary hypertension of the newborn (PPHN) with death or disability among infants with moderate or severe hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia. METHODS: We compared infants with and without PPHN enrolled in the hypothermia arm from three randomized controlled trials (RCTs): Induced Hypothermia trial, "usual care" arm of Optimizing Cooling trial, and Late Hypothermia trial. Primary outcome was death or disability at 18-22 months adjusted for severity of HIE, center, and RCT. RESULTS: Among 280 infants, 67 (24%) were diagnosed with PPHN. Among infants with and without PPHN, death or disability was 47% vs. 29% (adjusted OR: 1.65, 0.86-3.14) and death was 26% vs. 12% (adjusted OR: 2.04, 0.92-4.53), respectively. CONCLUSIONS: PPHN in infants with moderate or severe HIE was not associated with a statistically significant increase in primary outcome. These results should be interpreted with caution given the limited sample size.

Clearance prediction for Amgen molecules against Extended Clearance Classification System (ECCS) and future directions.

Early prediction of elimination pathways for new chemical entities can have a profound impact on drug discovery programs. The recently proposed Extended Clearance Classification System (ECCS) is a step in the right direction, providing a framework to help identify the major elimination pathway of a drug. A list of 42 Amgen small molecules was evaluated against the ECCS framework to assess its performance in retrospectively predicting their major elimination pathway. Here, we present a critical analysis of the chemical space defined by the ECCS framework with the aim of identifying its applicability and constraints. This evaluation highlights the critical need for periodic review and revision of ECCS, given that target constraints are moving molecules away from the traditional 'drug-like' physicochemical space.

Structural characterization and developability assessment of sustained release hydrogels for rapid implementation during preclinical studies.

Sustained-release formulations are important tools to convert efficacious molecules into therapeutic products. Hydrogels enable the rapid assessment of sustained-release strategies, which are important during preclinical development where drug quantities are limited and fast turnaround times are the norm. Most research in hydrogel-based drug delivery has focused around synthesizing new materials and polymers, with limited focus on structural characterization, technology developability and implementation. Two commercially available thermosensitive hydrogel systems, comprised of block copolymers of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PLGA) and poly(lactide-co-caprolactone)-b-poly(ethyleneglycol)-b-poly(lactide-co-caprolactone) (PLCL), were evaluated during this study. The two block copolymers described in the study were successfully formulated to form hydrogels which delayed the release of lysozyme (> 20 days) in vitro. Characterization of formulation attributes of the hydrogels like Tsol-gel temperature, complex viscosity and injection force showed that these systems are amenable to rapid implementation in preclinical studies. Understanding the structure of the gel network is critical to determine the factors controlling the release of therapeutics out of these gels. The structures were characterized via the gel mesh sizes, which were estimated using two orthogonal techniques: small angle X-ray scattering (SAXS) and rheology. The mesh sizes of these hydrogels were larger than the hydrodynamic radius (size) of lysozyme (drug), indicating that release through these gels is expected to be diffusive at all time scales rather than sub-diffusive. In vitro drug release experiments confirm that diffusion is the dominating mechanism for lysozyme release; with no contribution from degradation, erosion, relaxation, swelling of the polymer network or drug-polymer interactions. PLGA hydrogel was found to have a much higher complex viscosity than PLCL hydrogel, which correlates with the slower diffusivity and release of lysozyme seen from the PLGA hydrogel as compared to PLCL hydrogel. This is due to the increased frictional drag experienced by the lysozyme molecule in the PLGA hydrogel network, as described by the hydrodynamic theory.

Bringing Health Care Closer to People - A Review of Various Telemedicine Models under the National Health Mission in India.

Telemedicine is an alliance between technology and medicine. It is a prevalent practice in developed countries; it has been widely used in developing countries to address the issues of access to medical care. India has been experimenting with telemedicine since long to address the issues of access and availability of specialist care and in recent years, with the rapid advancement of information technology, telemedicine has become a popular concept across the country. In this article, we have reviewed the various aspects of different government-funded telemedicine models functional in 12 states across India. We have also attempted to explore the levels of care delivery and services at facilities provided through telemedicine and challenges being faced in the implementation of the models. As a way forward, the health-care community needs to realize the full potential of telemedicine facility and utilize it to their benefit. Telemedicine will work best when it is one component of a well-functioning health system and not as an isolated gap-filling application.

Prevalence and predictors of adverse reactions in plateletpheresis donors with the perspective of donor safety in a tertiary care hospital of Northern India.

BACKGROUND: Plateletpheresis procedures are generally safe and associated with low adverse reactions. Although donor reactions and injuries are self-limited events, they may discourage donors from future platelet donations. AIM: The purpose of this study was to determine the prevalence and predictors of adverse donor reactions in plateletpheresis donors, which could serve as targets for interventions to reduce reactions. MATERIALS AND METHODS: The study included 106 platelet donors over a period of 2 years. The demographic, biometric, and clinical parameters were noted. The data were analyzed for predictors of adverse donor reactions. STATISTICAL ANALYSIS USED: The data were analyzed using independent sample t-test to correlate donor variables such as gender. To correlate other variables such as age, weight, and whole blood processed, Chi-square test was used. RESULTS: A total of 106 plateletpheresis donations were performed and 13.2% of vasovagal reactions were observed. The significant predictive factors for reactions were young female donors with low body weight in which more than 2.5 L volume of whole blood was processed and more than 250 ml of acid, citrate, and dextrose-A was infused and with single venous access procedures. CONCLUSIONS: The results of this study are encouraging and helpful in identifying donors at risk for developing adverse reactions during plateletpheresis so that proper and close observation during and after donation as well as timely intervention can prevent most of the unpleasant events of plateletpheresis donors.

Role of Nanomaterials for Forensic Investigation and Latent Fingerprinting-A Review.

The imminent nanotechnology and progressive instrumentations together have vast applications in the field of forensic science. Few prominent examples are gold nanoparticles for improvising the efficiency of polymerase chain reaction and atomic force microscopy for examining ink and bloodstains. Characteristics like distinct ridge details of fingerprints could be obtained by applying different nanoparticles such as silver, zinc oxide, silicon dioxide, aluminum oxide, gold (with silver physical developer), europium, fluorescent carbon, and amphiphilic silica on a range of object surfaces, and among all, gold is most commonly used. Fingerprint is considered noteworthy evidence in any crime scene, and nano-based techniques hold immense future potential in fingerprint investigations. Therefore, this paper focuses on the applications of nanoparticles in developing and detecting the latent fingerprints.

Thromboelastography-Guided Blood Component Use in Patients With Cirrhosis With Nonvariceal Bleeding: A Randomized Controlled Trial.

Thromboelastography (TEG) provides a more comprehensive global coagulation assessment than routine tests (international normalized ratio [INR] and platelet [PLT] count), and its use may avoid unnecessary blood component transfusion in patients with advanced cirrhosis and significant coagulopathy who have nonvariceal upper gastrointestinal (GI) bleeding. A total of 96 patients with significant coagulopathy (defined in this study as INR >1.8 and/or PLT count < 50 × 109 /L) and nonvariceal upper GI bleed (diagnosed after doing upper gastrointestinal endoscopy, which showed ongoing bleed from a nonvariceal source) were randomly allocated to TEG-guided transfusion strategy (TEG group; n = 49) or standard-of-care (SOC) group (n = 47). In the TEG group, only 26.5% patients were transfused with all three blood components (fresh frozen plasma [FFP], PLTs, and cryoprecipitate) versus 87.2% in the SOC group (P < 0.001). Although 7 (14.3%) patients in the TEG group received no blood component transfusion, there were no such patients in the SOC group (P = 0.012). Also, there was a significantly lower use of blood components (FFP, PLTs, and cryoprecipitate) in the TEG group compared with the SOC group. Failure to control bleed, failure to prevent rebleeds, and mortality between the two groups were similar. Conclusion: In patients with advanced cirrhosis with coagulopathy and nonvariceal upper GI bleeding, TEG-guided transfusion strategy leads to a significantly lower use of blood components compared with SOC (transfusion guided by INR and PLT count), without an increase in failure to control bleed, failure to prevent rebleed, and mortality.

Three-Dimensional-Printed Model-Assisted Management of Craniovertebral Junction Abnormalities: An Institutional Experience with Literature Review.

STUDY DESIGN: Prospective study. PURPOSE: To evaluate the utility and limitations of using three-dimensional (3D)-printed models for the management of craniovertebral (CV) junction abnormalities. OVERVIEW OF LITERATURE: In comparison to other bony and vascular anomalies, CV junction abnormalities are difficult to treat. For cases of irreducible atlantoaxial dislocation (AAD), posterior reduction and stabilization have replaced anterior decompression as the standard management protocol. The use of 3D models, such as those described herein, can provide surgeons with in-depth knowledge of the vertebral artery course and bony anomalies associated with CV junction abnormalities. METHODS: Clinical and radiological features of 18 patients with CV junction abnormalities were analyzed between March 2017 and February 2019 at Sawai Man Singh Medical College, Jaipur, India. Dynamic computed tomography (CT) of the CV junction and CT angiographies of the neck with respect to the vertebral artery course at the C1-C2 joints were obtained and studied. Customized 3D models of the CV junction were then made based on the CT data, and rehearsal of the surgical procedure was performed using the 3D model one day prior to performing the actual procedure. RESULTS: Seventeen patients had congenital-type AAD, whereas one patient had posttraumatic AAD. Improvements in neck pain and myelopathy were seen in all patients at the follow-up, as analyzed using the Visual Analog Scale and the Japanese Orthopedic Association Scale score, respectively. There were no cases of malpositioning of screws or any direct vertebral artery injury, although in one patient, the distal flow in the dominant vertebral artery was cut off as it got compressed between the bony arch and the screw head. CONCLUSIONS: Compared to computer-generated images, 3D-printed models are a more practical approach for dealing with complex CV junction abnormalities. They provide surgeons with deep insights into the complex bony anomalies as well as variations in the vertebral artery courses, thereby improving surgical outcomes.

Treatment with carvedilol improves survival of patients with acute-on-chronic liver failure: a randomized controlled trial.

BACKGROUND AND AIMS: In addition to the portal pressure reducing effect, non-selective beta blockers (NSBBs) have possible immunomodulatory and effect in reducing bacterial translocation. Recently, it has been shown that patients who are already on NSBBs should be continued on them (if feasible), if acute-on-chronic liver failure (ACLF) develops. It, however, remains unknown if patients with ACLF and no or small esophageal varices at presentation will benefit from the use of NSBBs. We studied the efficacy and safety of carvedilol in patients with ACLF in reducing mortality, variceal bleeding and non-bleeding complications. METHODS: 136 patients with ACLF (with no or small esophageal varices and HVPG ≥ 12 mmHg) were randomized to either carvedilol (n = 66) or placebo arms (n = 70). RESULTS: Within 28 days, 7 (10.6%) of 66 patients in the carvedilol group and 17 (24.3%) of 70 in the placebo group died (p= 0.044). Fewer patients in the carvedilol compared to placebo group developed acute kidney injury (AKI) (13.6% vs 35.7%, p = 0.003 and spontaneous bacterial peritonitis (SBP) (6.1% vs 21.4%, p= 0.013). Significantly, more patients in the placebo group had increase in APASL ACLF Research Consortium-ACLF grade (22.9% vs 6.1%, p= 0.007). There was no significant difference in the 90-day transplant-free survival rate and development of AKI, SBP, non-SBP infections (including pneumonia) and variceal bleed within 90 days, between the two groups. CONCLUSIONS: In ACLF patients with either no or small esophageal varices and HVPG ≥ 12 mmHg, carvedilol leads to improved survival and fewer AKI and SBP events up to 28 days. CLINICALTRIALS. GOV IDENTIFIER NUMBER: NCT02583698.

Echocardiographic prediction of severe pulmonary hypertension in neonates undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy.

OBJECTIVE: Among neonates undergoing whole body cooling for hypoxic-ischemic encephalopathy (HIE), to compare ventricular function in the presence and absence of pulmonary hypertension (PPHN) needing inhaled nitric oxide (iNO)/ECMO. DESIGN: This retrospective study included infants with HIE who underwent cooling. ECHO (<24 h age) measures, RV fractional area change (FAC), RV Tricuspid annular plane systolic excursion (TAPSE), myocardial performance indices (MPI), and the RV systolic to diastolic duration (S/D) ratio were evaluated. RESULTS: The iNO/ECMO group (n = 26) had lower TAPSE and RV FAC and higher RV MPI and S/D, compared with controls (n = 39). Area under the curve was highest for RV S/D, with fair sensitivity (95% CI) [76.9 (56.3-91%)] and negative predictive value [78.6 (63.3-88.6%)] for subsequent iNO/ECMO at cutoff >1.45. CONCLUSIONS: Infants with HIE undergoing cooling who progressed to iNO/ECMO for PPHN had RV dysfunction on early ECHO; S/D had the best predictive performance. RV S/D may be a useful early marker of PPHN in HIE.

Hydrops Fetalis and Persistent Pulmonary Hypertension in a Neonate with Anti-E Alloimmunization.

Anti-E alloimmunization is the third most common cause of neonatal hemolytic disease, typically causing mild to moderate hemolytic anemia. We report an unusual case of severe hydrops fetalis and persistent pulmonary hypertension (PPHN) in a neonate with anti-E alloimmunization. Our case emphasizes the importance of close surveillance for development of severe fetal hemolytic anemia and possible need for antenatal intervention. These neonates may also need vigilant monitoring for PPHN.