Epidemiology, Clinical Characteristics, and Prognostic Factors in Critically Ill Patients with Hematolymphoid Malignancy.

OBJECTIVE: Despite advances in the field of oncology and intensive care, the outcomes of hematolymphoid malignancy (HLM) patients admitted to ICU are poor. This study was carried out to look at the demographic data, clinical features, and predictors of hospital mortality in these patients. MATERIALS AND METHODS: We prospectively studied 101 adult critically ill patients with HLM admitted to the 14-bedded mixed medical surgical ICU of a tertiary care cancer center. Out of 101 patients, end-of-life care decisions were taken in 7 patients, who were excluded from the outcome analysis. Predictors of in-hospital mortality were evaluated using univariate and multivariate analysis. RESULTS: The ICU and in-hospital mortality recorded in our study were 48.9 and 54.3%, respectively. Neutropenia at ICU admission, Simplified Acute Physiology Score III (SAPS III) score, and mechanical ventilation (MV) within 24 hours of ICU admission were associated with in-hospital mortality on univariate analysis. On multivariate logistic regression analysis, neutropenia at ICU admission (OR 4.621; 95% CI, 1.2-17.357) and MV within 24 hours of ICU admission (OR 2.728; 95% CI, 1.077-6.912) were independent predictors of in-hospital mortality. CONCLUSION: The HLM patients needing critical care have high acuity of illness, and acute respiratory failure is the commonest reason for ICU admission in these patients. In our study, the ICU survival was more than 50% and more than 45% patients were discharged alive from the hospital. We found a need for MV within 24 hours of ICU admission and presence of neutropenia at ICU admission to be independent predictors of hospital mortality in our study. HOW TO CITE THIS ARTICLE: Siddiqui SS, Prabu NR, Chaudhari HK, Narkhede AM, Sarode SV, Dhundi U, et al. Epidemiology, Clinical Characteristics, and Prognostic Factors in Critically Ill Patients with Hematolymphoid Malignancy. Indian J Crit Care Med 2021;25(1):56-61.

Is Immature Granulocyte Count a Potential Prognostic Marker for Upper Gastrointestinal Tract Bleeding? A New Road to Explore.

How to cite this article: Prabu NR, Patil VP. Is Immature Granulocyte Count a Potential Prognostic Marker for Upper Gastrointestinal Tract Bleeding? A New Road to Explore. Indian J Crit Care Med 2020;24(9):750-752.

Evaluation and Validation of Four Scoring Systems: the APACHE IV, SAPS III, MPM0 II, and ICMM in Critically Ill Cancer Patients.

BACKGROUND AND AIMS: To evaluate and validate four severity-of-illness scores, acute physiology and chronic health evaluation IV (APACHE IV), simplified acute physiology score III (SAPS III), mortality probability models II at 0 hours (MPM0 II), and ICU cancer mortality model (ICMM), in a prospective cohort of critically ill cancer patients. MATERIALS AND METHODS: Single-center, prospective observational study performed in a 14-bedded combined medical-surgical ICU of a tertiary care cancer center of India, from July 2014 to November 2015. Score performance was judged by discrimination and calibration, using the area under receiver-operating characteristics (ROC) curve and Hosmer-Lemeshow goodness-of-fit test, respectively. RESULTS: A total of 431 patients were included in the study. Intensive care unit (ICU) and hospital mortality were 37.4% and 41.1%, respectively. The area under ROC curve for APACHE IV, SAPS III, MPM0 II, and ICMM were 0.73, 0.70, 0.67, and 0.67, respectively. Calibration as calculated by Hosmer-Lemeshow analysis type C statistics for APACHE IV, SAPS III, MPM0 II, and ICMM shows good calibration with Chi-square values of 5.32, 9.285, 9.873, and 9.855 and p values of 0.723, 0.319, 0.274, and 0.275, respectively. CONCLUSION: All the four models had moderate discrimination and good calibration. However, none of the mortality prediction models could accurately discriminate between survivors and nonsurvivors in our patients. HOW TO CITE THIS ARTICLE: Siddiqui SS, Narkhede AM, Kulkarni AP, Prabu NR, Chaudhari HK, Divatia JV, et al. Evaluation and Validation of Four Scoring Systems: the APACHE IV, SAPS III, MPM0 II, and ICMM in Critically Ill Cancer Patients. Indian J Crit Care Med 2020;24(4):263-269.

Benefits of and Untoward Events during Intrahospital Transport of Pediatric Intensive Care Unit Patients.

BACKGROUND AND AIMS: The transport of critically ill patients for procedures or imaging outside the Intensive Care Unit (ICU) is potentially hazardous; hence, the transport process must be organized and efficient. The literature about benefits of and untoward events (UEs) during intrahospital transport of pediatric critically ill patient is scarce. We, therefore, audited the UEs during and benefits of intrahospital transport of critically ill pediatric patients in our ICU. SUBJECTS AND METHODS: Eighty critically ill pediatric (<18 years) cancer patients, transported from the ICU for either diagnostic or therapeutic procedure over a period of 6 months, were included in the study. The data collected included the destination (computed tomography scan, intervention radiology, magnetic resonance imaging scan, and operation theater), accompanying medical personnel, UEs, and benefits obtained during transport. RESULTS: Among eighty pediatric patients, the median age was 8 years (range 2-17 years). During the transport, four (5%) patients required endotracheal intubation, three (3.75%) patients required intercostal drain placement, and six (7.5%) patients required cardiopulmonary resuscitation. Accidental removal of central venous catheter was reported in three (3.75%) patients, drain came out in four (5%) patients, and three (3.75%) patients had accidental extubation. Transport indirectly led to a change in antibiotic therapy in 24 (30%) patients and directly helped in change of therapy in the form of interventions in 20 (25%) patients. CONCLUSION: Critically ill children can be transported safely with adequate pretransport preparations, which may help in avoiding major UEs and benefit the patient by change in the therapy.

The Changes in Pulse Pressure Variation or Stroke Volume Variation After a "Tidal Volume Challenge" Reliably Predict Fluid Responsiveness During Low Tidal Volume Ventilation.

OBJECTIVES: Stroke volume variation and pulse pressure variation do not reliably predict fluid responsiveness during low tidal volume ventilation. We hypothesized that with transient increase in tidal volume from 6 to 8 mL/kg predicted body weight, that is, "tidal volume challenge," the changes in pulse pressure variation and stroke volume variation will predict fluid responsiveness. DESIGN: Prospective, single-arm study. SETTING: Medical-surgical ICU in a university hospital. PATIENTS: Adult patients with acute circulatory failure, having continuous cardiac output monitoring, and receiving controlled low tidal volume ventilation. INTERVENTIONS: The pulse pressure variation, stroke volume variation, and cardiac index were recorded at tidal volume 6 mL/kg predicted body weight and 1 minute after the "tidal volume challenge." The tidal volume was reduced back to 6 mL/kg predicted body weight, and a fluid bolus was given to identify fluid responders (increase in cardiac index > 15%). The end-expiratory occlusion test was performed at tidal volumes 6 and 8 mL/kg predicted body weight and after reducing tidal volume back to 6 mL/kg predicted body weight. RESULTS: Thirty measurements were obtained in 20 patients. The absolute change in pulse pressure variation and stroke volume variation after increasing tidal volume from 6 to 8 mL/kg predicted body weight predicted fluid responsiveness with areas under the receiver operating characteristic curves (with 95% CIs) being 0.99 (0.98-1.00) and 0.97 (0.92-1.00), respectively. The best cutoff values of the absolute change in pulse pressure variation and stroke volume variation after increasing tidal volume from 6 to 8 mL/kg predicted body weight were 3.5% and 2.5%, respectively. The pulse pressure variation, stroke volume variation, central venous pressure, and end-expiratory occlusion test obtained during tidal volume 6 mL/kg predicted body weight did not predict fluid responsiveness. CONCLUSIONS: The changes in pulse pressure variation or stroke volume variation obtained by transiently increasing tidal volume (tidal volume challenge) are superior to pulse pressure variation and stroke volume variation in predicting fluid responsiveness during low tidal volume ventilation.

Complications and benefits of intrahospital transport of adult Intensive Care Unit patients.

BACKGROUND: The transport of critically ill patients for procedures or tests outside the Intensive Care Unit (ICU) is potentially hazardous; hence, the transport process must be organized and efficient. Plenty of data is available on pre- and inter-hospital transport of patients; the data on intrahospital transport of patients are limited. We audited the complications and benefits of intrahospital transport of critically ill patients in our tertiary care center over 6 months. MATERIALS AND METHODS: One hundred and twenty adult critically ill cancer patients transported from the ICU for either diagnostic or therapeutic procedure over 6 months were included. The data collected include the destination, the accompanying person, total time spent outside the ICU, and any adverse events and adverse change in vitals. RESULTS: Among the 120 adult patients, 5 (4.1%) required endotracheal intubation, 5 (4.1%) required intercostal drain placement, and 20 (16.7%) required cardiopulmonary resuscitation (CPR). Dislodgement of central venous catheter occurred in 2 (1.6%) patients, drain came out in 3 (2.5%) patients, orogastric tube came out in 1 (0.8%) patient, 2 (1.6%) patients self-extubated, and in one patient, tracheostomy tube was dislodged. The adverse events were more in patients who spent more than 60 min outside the ICU, particularly requirement of CPR (18 [25%] vs. 2 [4.2%], ≤60 min vs. >60 min, respectively) with P < 0.05. Transport led to change in therapy in 32 (26.7%) patients. CONCLUSION: Transport in critically ill cancer patients is more hazardous and needs adequate pretransport preparations. Transport in spite being hazardous may lead to a beneficial change in therapy in a significant number of patients.

Structure of angiotensin I-converting enzyme.

Angiotensin-converting enzyme (ACE) is a zinc- and chloride-dependent metallopeptidase that plays a vital role in the metabolism of biologically active peptides. Until recently, much of the inhibitor design and mechanism of action of this ubiquitous enzyme was based on the structures of carboxypeptidase A and thermolysin. When compared to the recently solved structures of the testis isoform of ACE (tACE) and its Drosophila homologue (AnCE), carboxypeptidase A showed little structural homology outside of the active site, while thermolysin revealed significant but less marked overall similarity. The ellipsoid-shaped structure of tACE, which has a preponderance of alpha-helices, is characterised by a core channel that has a constriction approximately 10 A from its opening where the zinc-binding active site is located. Comparison of the native protein with the inhibitor-bound form (lisinopril-tACE) does not reveal any striking differences in the conformation of the inhibitor binding site, disfavouring an open and closed configuration. However, the inhibitor complex does provide insights into the network of hydrogen-bonding and ionic interactions in the active site as well as the mechanism of ACE substrate hydrolysis. The three-dimensional structure of ACE now paves the way for the rational design of a new generation of domain-selective ACE inhibitors.

Thermostable xylanase from Thermoascus aurantiacus at ultrahigh resolution (0.89 A) at 100 K and atomic resolution (1.11 A) at 293 K refined anisotropically to small-molecule accuracy.

Thermoascus aurantiacus xylanase is a thermostable enzyme which hydrolyses xylan, a major hemicellulose component of the biosphere. The crystal structure of this F/10 family xylanase, which has a triosephosphate isomerase (TIM) barrel (beta/alpha)(8) fold, has been solved to small-molecule accuracy at atomic resolution (1.11 A) at 293 K (RTUX) and at ultrahigh resolution (0.89 A) at 100 K (CTUX) using X-ray diffraction data sets collected on a synchrotron light source, resulting in R/R(free) values of 9.94/12.36 and 9.00/10.61% (for all data), respectively. Both structures were refined with anisotropic atomic displacement parameters. The 0.89 A structure, with 177 476 observed unique reflections, was refined without any stereochemical restraints during the final stages. The salt bridge between Arg124 and Glu232, which is bidentate in RTUX, is water-mediated in CTUX, suggesting the possibility of plasticity of ion pairs in proteins, with water molecules mediating some of the alternate arrangements. Two buried waters present inside the barrel form hydrogen-bond interactions with residues in strands beta2, beta3, beta4 and beta7 and presumably contribute to structural stability. The availability of accurate structural information at two different temperatures enabled the study of the temperature-dependent deformations of the TIM-barrel fold of the xylanase. Analysis of the deviation of corresponding C(alpha) atoms between RTUX and CTUX suggests that the interior beta-strands are less susceptible to changes as a function of temperature than are the alpha-helices, which are on the outside of the barrel. betaalpha-loops, which are longer and contribute residues to the active-site region, are more flexible than alphabeta-loops. The 0.89 A structure represents one of the highest resolution structures of a protein of such size with one monomer molecule in the asymmetric unit and also represents the highest resolution TIM-barrel fold structure to date. It may provide a useful template for theoretical modelling studies of the structure and dynamics of the ubiquitous TIM-barrel fold.

Structure of UDP complex of UDP-galactose:beta-galactoside-alpha -1,3-galactosyltransferase at 1.53-A resolution reveals a conformational change in the catalytically important C terminus.

UDP-galactose:beta-galactosyl alpha-1,3-galactosyltransferase (alpha3GT) catalyzes the transfer of galactose from UDP-alpha-d-galactose into an alpha-1,3 linkage with beta-galactosyl groups in glycoconjugates. The enzyme is expressed in many mammalian species but is absent from humans, apes, and old world monkeys as a result of the mutational inactivation of the gene; in humans, a large fraction of natural antibodies are directed against its product, the alpha-galactose epitope. alpha3GT is a member of a family of metal-dependent retaining glycosyltransferases including the histo-blood group A and B synthases. A crystal structure of the catalytic domain of alpha3GT was recently reported (Gastinel, L. N., Bignon, C., Misra, A. K., Hindsgaul, O., Shaper, J. H., and Joziasse, D. H. (2001) EMBO J. 20, 638-649). However, because of the limited resolution (2.3 A) and high mobility of the atoms (as indicated by high B-factors) this structure (form I) does not provide a clear depiction of the catalytic site of the enzyme. Here we report a new, highly ordered structure for the catalytic domain of alpha3GT at 1.53-A resolution (form II). This provides a more accurate picture of the details of the catalytic site that includes a bound UDP molecule and a Mn(2+) cofactor. Significantly, in the new structure, the C-terminal segment (residues 358-368) adopts a very different, highly structured conformation and appears to form part of the active site. The properties of an Arg-365 to Lys mutant indicate that this region is important for catalysis, possibly reflecting its role in a donor substrate-induced conformational change.

Crystal structure at 1.8 A resolution and proposed amino acid sequence of a thermostable xylanase from Thermoascus aurantiacus.

Thermoascus aurantiacus xylanase is a thermostable enzyme which hydrolyses xylan, a major hemicellulose component in the biosphere. Crystals belonging to P21 space group with a=41.7 A, b=68.1 A, c=51. 4 A and beta=113.6 degrees, Z=2 were grown that could diffract to better than 1.8 A resolution. The structure was solved by molecular replacement method using the Streptomyces lividans xylanase model. The amino acid sequence was determined from the electron density map aided by multiple alignment of related xylanase sequences. The sequence thus obtained provides a correction to the sequence reported earlier based on biochemical methods. The final refined protein model at 1.8 A resolution with 301 amino acid residues and 266 water molecules has an R-factor of 16.0 % and free R of 21.1 % with good stereochemistry. The single polypeptide chain assumes (alpha/beta)8 TIM-barrel fold and belongs to F/10 family of glycoside hydrolases. The active site consists of two glutamate residues located at the C terminus end of the beta-barrel, conforming to the double displacement mechanism for the enzyme action. A disulphide bond and more than ten salt bridges have been identified. In particular, the salt bridge Arg124-Glu232 which is almost buried, bridges the beta-strands beta4 and beta7 where the catalytic glutamate residues reside, and it may play a key role in the stability and activity at elevated temperature. To our knowledge, for the first time in the F/10 family xylanases, we observe a proline residue in the middle of the alpha-helix alpha6 which may be contributing to better packing. Earlier studies show that the enzyme retains its activity even at 70 degrees C. The refined protein model has allowed a detailed comparison with the other known structures in the F/10 family of enzymes. The possible causative factors for thermostability are discussed.