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..

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.

ABCA12 homozygous mutation in harlequin ichthyosis: Survival without systemic retinoids.

Harlequin ichthyosis (HI) is associated with high mortality. Early systemic retinoids are widely used, although their use remains debatable. We reported two neonates with homozygous mutations in ABCA12 consistent with harlequin ichthyosis who survived to discharge home with intensive care and without use of systemic retinoids.

Comparison of Prognostic Models in Acute Liver Failure: Decision is to be Dynamic.

BACKGROUND AND AIMS: Acute liver failure (ALF) is a rare disease entity with a high mortality. Management is dependent on accurate prognostication. MATERIALS AND METHODS: One hundred consecutive patients presenting with ALF were prospectively evaluated. The King's college criteria (KCC), ALF early dynamic model (ALFED), sequential organ failure assessment (SOFA) score, and acute physiology and health evaluation II (APACHE II) scores were compared to predict mortality. RESULTS: There were significant differences in means of all the scores between survivors and nonsurvivors. The SOFA 48 hours had the highest area under receiver operating characteristic curve (AUC) (0.857) closely followed by the ALFED score (0.844). The optimal cutoff for the SOFA score at 48 hours to predict subsequent survival outcome is ≥10 and for the ALFED score is ≥5. Sequential organ failure assessment 48 hours had a good sensitivity of 87%, and the ALFED score showed a good specificity of 84%. The decision curve analysis showed that between a threshold probability of 0.13 and 0.6, use of the SOFA score provided the maximum net benefit and at threshold probabilities of >0.6, the use of ALFED score provided the maximum clinical benefit. CONCLUSION: Dynamic scoring results in better prognostication in ALF. The SOFA 48 hours and ALFED score have good prognostication value in nonacetaminophen-induced liver failure. HOW TO CITE THIS ARTICLE: Saluja V, Sharma A, Pasupuleti SSR, Mitra LG, Kumar G, Agarwal PM. Comparison of Prognostic Models in Acute Liver Failure: Decision is to be Dynamic. Indian J Crit Care Med 2019;23(12):574-581.

Surgical Interventions in Infants Born Preterm with Congenital Heart Defects: An Analysis of the Kids' Inpatient Database.

OBJECTIVE: To evaluate short-term outcomes in infants born preterm with congenital heart defects (CHDs) and the factors associated with surgery, survival, and length of hospitalization in this population. STUDY DESIGN: We analyzed data from infants born preterm (gestational age <37 weeks) enrolled in the multicenter Kids' Inpatient Database of the Healthcare Cost and Utilization Project who were admitted to the hospital within 30 days after birth. Infants with atrial septal defects were excluded. RESULTS: Of 1 429 762 enrolled infants born preterm, 27 434 (2.0%) with CHDs were included. Overall survival to discharge was 90.5%; 74.0% among infants with critical CHDs and 45.7% among infants with hypoplastic left heart syndrome. Cardiac surgeries were performed in 12.2% of all infants born preterm. Rates of surgical intervention for infants with critical CHDs were lower for very low birth weight (≤1.5 kg) vs larger infants >1.5 kg (27% vs 44%), and only 6.3% of infants born with very low birth weight underwent surgeries in Risk-adjustment for Congenital Heart Surgery categories 4 or greater. Greater birth weight, left-sided lesions, care at children's hospitals, and absence of trisomies were associated with a greater likelihood of surgery. Birth weight <2 kg, nonwhite race, trisomy syndromes, prematurity-related morbidities, and Risk-adjustment for Congenital Heart Surgery category 4 or greater were independent predictors of mortality. Birth weight <2 kg, Risk-adjustment for Congenital Heart Surgery category, morbidities, and sidedness of lesion predicted length of stay. CONCLUSIONS: The high survival rates of infants born preterm with CHDs suggests that a cautiously optimistic approach to surgery may be warranted in all but the most immature infants with the greatest-risk conditions.

CNS delivery of targeted protein degraders.

Heterobifunctional small molecule degraders are a subset of targeted protein degraders (TPDs), consisting of two ligands joined by a linker to induce proteasomal degradation of a target protein. As compared to traditional small molecules these compounds generally demonstrate inflated physicochemical properties, which may require innovative formulation strategies to enable their delivery and exert pharmacodynamic effect. The blood brain barrier (BBB) serves an essential function in human physiology, but its presence requires advanced approaches for treating central nervous system (CNS) diseases. By integrating emerging modalities like TPDs with conventional concepts of drug delivery, novel strategies to overcome the BBB can be developed. Amongst the available routes, lipid and polymer-based long-acting delivery seems to be the most amenable to TPDs, due to their ability to encapsulate lipophilic cargo and potential to be functionalized for targeted delivery. Another key consideration will be understanding E3 ligase expression in the different regions of the brain. Discovery of new brain or CNS disease specific E3 ligases could help overcome some of the barriers currently associated with CNS delivery of TPDs. This review discusses the current strategies that exist to overcome and improve therapeutic delivery of TPDs to the CNS.

Prestorage gamma irradiation induces oxidative injury to red cells.

BACKGROUND: Gamma irradiation of blood results in the formation free radicals, which interact with lipids and proteins in the membranes of red blood cells. We have investigated oxidative injury to gamma-irradiated red cells by measuring markers of oxidative injury and its correlation with red cell membrane damage. METHODS: Thirty red cell blood units were irradiated at 25 Gy using Gamma Irradiator (Nordion, Canada) and stored at 4°C for 28 days. Markers of oxidative injury such as MDA levels, methemoglobin formation and osmotic fragility and markers of membrane damage including supernatant Hb, supernatant K(+), and LDH were studied. RESULTS: There was a progressive and statistically significant increase in markers of oxidative injury such as MDA (3.76 v/s 5.01), and methemoglobin formation (1.87 v/s 3.58) in irradiated red cells compared to control non-irradiated cells. Exposure to gamma irradiation caused significant increase in markers of hemolysis such as supernatant Hb (0.087 v/s 0.363), K(+) (35.1 v/s 51.2) and LDH (366.9 v/s 587.4) over the storage period of 28 days. CONCLUSION: Gamma irradiation increases lipid peroxidation and oxidative injury to the red cells.

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.

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.

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.

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.

Quantification of feto-maternal hemorrhage: selection of techniques for a resource-poor setting.

BACKGROUND: Though RhD sensitization in RhD-negative mothers is now almost eradicated in the developed world, it continues to be a major health problem in developing nations like India. Inadequate immunoprophylaxis is the main reason. Adequate dose calculation of anti-D Ig is possible through estimation of correct feto-maternal hemorrhage (FMH) volume. In this regard, different methods have been used. METHODS: We evaluated three quantitative techniques of estimating FMH: the Kleihauer-Betke test (KBT) and two flow cytometry (FC) techniques, i.e., the indirect immunofluorescence technique (IIFT) and direct immunofluorescence technique (DIFT). Stock solutions of both RhD-positive and D-negative cells were made, and 7 serial dilutions of RhD-positive cord cells in D-negative adult cells were prepared. RESULT: Both KBT and FC approximated the expected concentration of fetal RhD-positive cells in all mixtures tested. In both methods, an underestimation of fetal RhD-positive cells was observed when their expected concentration was ≥0.75%. CONCLUSION: Though FC is the most sensitive of all techniques, very few laboratories in developing nations can afford such a costly device, so it will be prudent for them to use KBT as the gold standard due to its rapidity, simplicity and affordability.

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.

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.

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.

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.

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.

Seroprevalence of Toxoplasma gondii antibodies in North Indian blood donors: implications for transfusion transmissible toxoplasmosis.

INTRODUCTION: Transfusion transmitted Toxoplasma gondii (T. gondii) can result in significant clinical consequences in immunocompromised and multiply transfused patients, pregnant women and fetus etc. Anti-T. gondii seroprevalence, specifically IgM antibodies reflect the risk of transfusion transmission. METHODS: Four hundred and ninety-three blood donors in a tertiary care hospital in North India were screened for IgG and IgM anti-T. gondii antibodies by enzyme linked immunosorbent assay (ELISA). RESULTS: The prevalence of IgG and IgM anti-T. gondii antibodies was 51.8% and 5% respectively. The prevalence was higher in females (M=51.6%, F=89.2%) and in replacement donors (replacement donors=63.2%, voluntary donors=33.5%). CONCLUSION: The donor population constitutes a significant risk of transfusion transmitted toxoplasmosis. Effective strategies are required to prevent transfusion transmitted toxoplasmosis.

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.