DNA N-glycosylases Ogg1 and EndoIII as components of base excision repair in Plasmodium falciparum organelles.

The integrity of genomes of the two crucial organelles of the malaria parasite - an apicoplast and mitochondrion in each cell - must be maintained by DNA repair mediated by proteins targeted to these compartments. We explored the localisation and function of Plasmodium falciparum base excision repair (BER) DNA N-glycosylase homologs PfEndoIII and PfOgg1. These N-glycosylases would putatively recognise DNA lesions prior to the action of apurinic/apyrimidinic (AP)-endonucleases. Both Ape1 and Apn1 endonucleases have earlier been shown to function solely in the parasite mitochondrion. Immunofluorescence localisation showed that PfEndoIII was exclusively mitochondrial. PfOgg1 was not seen clearly in mitochondria when expressed as a PfOgg1leader-GFP fusion, although chromatin immunoprecipitation assays showed that it could interact with both mitochondrial and apicoplast DNA. Recombinant PfEndoIII functioned as a DNA N-glycosylase as well as an AP-lyase on thymine glycol (Tg) lesions. We further studied the importance of Ogg1 in the malaria life cycle using reverse genetic approaches in Plasmodium berghei. Targeted disruption of PbOgg1 resulted in loss of 8-oxo-G specific DNA glycosylase/lyase activity. PbOgg1 knockout did not affect blood, mosquito or liver stage development but caused reduced blood stage infection after inoculation of sporozoites in mice. A significant reduction in erythrocyte infectivity by PbOgg1 knockout hepatic merozoites was also observed, thus showing that PbOgg1 ensures smooth transition from liver to blood stage infection. Our results strengthen the view that the Plasmodium mitochondrial genome is an important site for DNA repair by the BER pathway.

Early radiological outcomes of a fully porous bridging collar in lower-limb endoprosthetic reconstructions: a case-matched retrospective series to assess osseointegration.

BACKGROUND: Limb-salvage surgery involving the utilization of endoprosthetic replacements is commonly employed following segmental bone resection for primary and secondary bone tumors. This study aimed to evaluate whether a fully porous bridging collar promotes early osseous integration in endoprosthetic replacements. METHODS: We undertook a retrospective review of all lower-limb endoprostheses utilizing a fully porous endosteal bridging collar design. We matched this cohort with a conventional extra-osteal non-porous fully hydroxyapatite-coated grooved collar cohort according to surgical indication, implant type, resection length, age, and follow-up time. At 6, 12, and 24 months post-implantation, radiographs were assessed for the number of cortices with or without osseointegration on orthogonal radiographs. Each radiograph was scored on a scale of -4 to + 4 for the number of cortices bridging the ongrowth between the bone and the collar of the prosthesis. Implant survival was estimated using the Kaplan-Meier method, and the mean number of osseointegrated cortices at each time point between the collar designs was compared using a paired t-test. RESULTS: Ninety patients were retrospectively identified and analyzed. After exclusion, 40 patients with porous bridging collars matched with 40 patients with conventional extra-osteal non-porous collars were included in the study (n = 80). The mean age was 63.4 years (range 16-91 years); there were 37 males and 43 females. The groups showed no difference in implant survival (P = 0.54). The mean number of cortices with radiographic ongrowth for the porous bridging collar and non-porous collar groups was 2.1 and 0.3, respectively, at 6-month (P < 0.0001), 2.4 and 0.5, respectively, at 12-month (P = 0.044), and 3.2 and -0.2, respectively, at 24-month (P = 0.18) radiological follow-up. CONCLUSION: These findings indicate that fully porous bridging collars increased the number of cortices, with evidence of bone ongrowth between 6 and 24 months post-implantation. By contrast, extra-osteal collars exhibited reduced evidence of ongrowth between 6 and 24 months post-implantation. In the medium term, the use of a fully porous bridging collar may translate to a reduced incidence of aseptic loosening.

Identification of novel inhibitors targeting TIRAP interactions with BTK and PKCδ in inflammation through an in silico approach.

Advanced computational tools focusing on protein-protein interaction (PPI) based drug development is a powerful platform to accelerate the therapeutic development of small lead molecules and repurposed drugs. Toll/interleukin-1 receptor (TIR) domain-containing adapter protein (TIRAP) and its interactions with other proteins in macrophages signalling are crucial components of severe or persistent inflammation. TIRAP activation through Bruton's tyrosine kinase (BTK) and Protein Kinase C delta (PKCδ) is essential for downstream inflammatory signalling. We created homology-based structural models of BTK and PKCδ in MODELLER 9.24. TIRAP interactions with BTK and PKCδ in its non-phosphorylated and phosphorylated states were determined by multiple docking tools including HADDOCK 2.4, pyDockWEB and ClusPro 2.0. Food and Drug Administration (FDA)-approved drugs were virtually screened through Discovery Studio LibDock and Autodock Vina tools to target the common TIR domain residues of TIRAP, which interact with both BTK and PKC at the identified interfacial sites of the complexes. Four FDA-approved drugs were identified and found to have stable interactions over a range of 100 ns MD simulation timescales. These drugs block the interactions of both kinases with TIRAP in silico. Hence, these drugs have the potential to dampen downstream inflammatory signalling and inflammation-mediated disease.

Clinical Impact of the Early Use of Monoclonal Antibody LY-CoV555 (Bamlanivimab) on Mortality and Hospitalization Among Elderly Nursing Home Patients: A Multicenter Retrospective Study.

Importance Coronavirus disease 2019 (COVID-19) outbreaks are frequent occurrences in nursing homes and long-term care facilities (LTCFs), resulting in subsequent hospitalization and death. Rationale Virus-neutralizing monoclonal antibodies demonstrate a significant decrease in both viral load and hospital transfer rate among patients with mild-to-moderate COVID-19 infection. Objective To assess the clinical outcomes of COVID-19 patients with mild-to-moderate symptoms in LTCFs who received LY-CoV555 as compared to those who did not receive this treatment. Design Retrospective case-control study and logistic regression analysis. Setting LTCFs in New York. Participants Two-hundred forty-six (246) LTCF patients diagnosed with mild-to-moderate COVID-19 infection with positive COVID-19 polymerase chain reaction (PCR) from November 15, 2020, to January 31, 2021. Methods Two-hundred forty-six (246) COVID-19 patients were identified from electronic medical records, out of which 160 cases were exposed to LY-CoV555 treatment (700 mg single dose, intravenous infusion). Eighty-six (86) patients were unexposed controls who did not receive monoclonal antibodies, LY-CoV555. Outcome We assessed the odds of death and hospitalization of exposed cases as compared to unexposed controls. Using logistic regression analysis, we also assessed the risk factors associated with these outcomes in the entire sample population. Results The mean age of the entire sample was 82.4 years. Fifty-two percent (52%) of patients (n = 129) were female and 48% (n = 117) were male. The mean ages of the exposed group and the unexposed group were 81 years and 84 years, respectively. At the end of the study, 92% (148/160) of the exposed group were alive or not transferred to the hospital as compared to 79% (68/86) patients of the unexposed group (OR 3.23, 95% CI: (1.48, 7.31), p-value = 0.0032). Three percent (3%; 5/160) of patients died in the exposed group compared to 10% (9/86) of patients who died in the unexposed group (OR = 0.25, 95% CI: (0.1, 0.85), p-value = 0.0257). Four point thirty-seven percent (4.37%; 7/160) of patients in the exposed group and 10.46% (9/86) of patients in the unexposed group were transferred to the hospital (OR = 0.35, 95% CI: (0.15, 1.08), p-value = 0.0793). Conclusion Early treatment with monoclonal antibody LY-CoV555 is associated with decreased mortality among high-risk patients with mild-to-moderate COVID-19 infection in LTCFs. Although not statistically significant, there was a trend towards a lower risk of hospitalization in patients treated with LY-CoV555.

The importance of low-dose CT screening to identify emphysema in asymptomatic participants with and without a prior diagnosis of COPD.

PURPOSE: Chronic Obstructive Pulmonary Disease (COPD) includes chronic bronchitis, small airways disease, and emphysema. Diagnosis of COPD requires spirometric evidence and may be normal even when small airways disease or emphysema is present. Emphysema increases the risk of exacerbations, and is associated with all-cause mortality and increased risk of lung cancer. We evaluated the prevalence of emphysema in participants with and without a prior history of COPD. METHODS: We reviewed a prospective cohort of 52,726 subjects who underwent baseline low dose CT screening for lung cancer from 2003 to 2016 in the International Early Lung Cancer Action Program. RESULTS: Of 52,726 participants, 23.8%(12,542) had CT evidence of emphysema. Of these 12,542 participants with emphysema, 76.5%(9595/12,542) had no prior COPD diagnosis even though 23.6% (2258/9595) had moderate or severe emphysema. Among 12,542 participants, significant predictors of no prior COPD diagnosis were: male (OR = 1.47, p < 0.0001), younger age (ORage10 = 0.72, p < 0.0001), lower pack-years of smoking (OR10pack-years = 0.90, p < 0.0001), completed college or higher (OR = 1.54, p < 0.0001), no family history of lung cancer (OR = 1.12, p = 0.04), no self-reported cardiac disease (OR = 0.76, p = 0.0003) or hypertension (OR = 0.74, p < 0.0001). The severity of emphysema was significantly lower among the 9595 participants with no prior COPD diagnosis, the OR for moderate emphysema was ORmoderate = 0.58(p = 0.0007) and for severe emphysema, it was ORsevere = 0.23(p < 0.0001). CONCLUSION: Emphysema was identified in 23.8% participants undergoing LDCT and was unsuspected in 76.5%. LDCT provides an opportunity to identify emphysema, and recommend smoking cessation.

Computational exploration and anti-mycobacterial activity of potential inhibitors of Mycobacterium tuberculosis acetyl coenzyme A carboxylase as anti-tubercular agents.

Acetyl Coenzyme A Carboxylase (AccD6) is a homodimeric protein which is involved in the carboxylation of acetyl coenzyme A to produce malonyl coenzyme A, which plays an important role in the biosynthesis of fatty acid chain. However, studies suggest that AccD6 in combination with AccA3 produces malonyl co-A. Certain herbicides are known to inhibit plant ACC. Among these herbicides, haloxyfop was found to inhibit AccD6 at IC50 of 21.1 ± 1 µM. In this study, we have performed molecular docking of the Maybridge database consisting of ~55,000 compounds in the active site of the protein with haloxyfop as a reference molecule, followed by molecular dynamics study and biological activity determination of prioritized compounds. Out of the nine compounds selected for biological evaluation, three compounds - CD07230, HTS08529 and KM08871 - were found to exhibit anti-mycobacterial activity.

A flexible silicone patch for treatment of hemorrhoids after birth: a pilot study of HEMOCIN® Patch.

PURPOSE: To test a non-pharmacological silicone patch for treatment of symptomatic hemorrhoids with focus on usability, safety, and self-reported short-term effect. METHODS: Puerperal women in a Danish maternity ward were cluster randomized to treatment with the HEMOCIN® patch (intervention) or no systematic treatment (control group). On inclusion and after 2 weeks, they completed a questionnaire regarding history and hemorrhoid symptoms scored from 0 to 10. Women in the intervention group also reported on the usability of the patch and any side effects. RESULTS: We included 31 women in the intervention group and 33 in the control group. Twenty-eight (90.3%) women in the intervention group and 27 (81.8%) women in the control group responded to follow-up. Except from a difference in the severity of swelling at inclusion, there were no differences between the two groups for any symptoms, neither at inclusion, nor at follow-up, or in the change of symptoms during the two weeks (p > 0.05). Twenty-three women (85.2%) in the control group used medical treatment vs. one woman in the intervention group. The patch was used on an average of 9.3 days, 15.5 h/day and for 7.1 h before changing the patch. No severe side effects were reported. CONCLUSION: This pilot study finds that the HEMOCIN® patch is a safe and feasible treatment option for hemorrhoids. However, we did not detect any significant effect on hemorrhoid symptoms. The patch could be an option for people who seek non-pharmacological treatment for symptomatic hemorrhoids or need long-term treatment without steroid side effects.

Mathematical model for plant-insect interaction with dynamic response to PAD4-BIK1 interaction and effect of BIK1 inhibition.

Plant-insect interaction system is a widely studied model of the ecosystem. Numerical understanding of this counter system has developed from initial analogy based approach with a predator-prey model to its recent mathematical interpretation including plant immunity concept. In current work, we propose an extension to this model, including molecular interactions behind the plant defense system and its effect on ecological behaviour. Inspired from biomolecular interaction given by Louis and Shah in 2014, we propose here a mathematical model to depict molecular dependence and control of plant insect interaction system. Insect infestation mediated Botrytis Induced Kinase-1 (BIK1) induction resulted in inhibition of Phyto Alexin Deficient-4 (PAD4) protein. Lowered PAD4 triggers the plant defense mechanism, leading to degraded plant immune potential and thereby reducing the plant quality. We mathematically adapt these interactions to show their influence on plant-insect interaction system and hypothesize the significance of BIK1 inhibition leading to the improved plant quality. We implemented the plethora of computational modeling and all atom MD simulations to explain the Plant-Insect-PAD4-BIK1 interaction network and identify potential molecular mechanisms of plant improvement by BIK1 inhibition.

Synthesis, biological evaluation and molecular dynamic simulations of novel Benzofuran-tetrazole derivatives as potential agents against Alzheimer's disease.

A series of novel Benzofuran-tetrazole derivatives were successfully synthesised by integrating multicomponent Ugi-azide reaction with the molecular hybridization approach. Interestingly, a number of synthesized derivatives (5c, 5d, 5i, 5l, 5q and 5s) exhibited significant reduction of aggregation of "human" amyloid beta peptide, expressing on transgenic Caenorhabditis elegans (C. elegans) strain CL4176. Further, in silico docking results have evidenced the exquisite interaction of active compounds with the help of TcAChE-E2020 complex. These findings underscore the potential of these hybrids as lead molecules against Alzheimers's disease.

A TLR4-derived non-cytotoxic, self-assembling peptide functions as a vaccine adjuvant in mice.

Vaccination is devised/formulated to stimulate specific and prolonged immune responses for long-term protection against infection or disease. A vaccine component, namely adjuvant, enhances antigen recognition by the host immune system and thereby stimulates its cellular and adaptive responses. Especially synthetic Toll-like receptor (TLR) agonists having self-assembling properties are considered as good candidates for adjuvant development. Here, a human TLR4-derived 20-residue peptide (TR-433), present in the dimerization interface of the TLR4-myeloid differentiation protein-2 (MD2) complex, displayed self-assembly and adopted a nanostructure. Both in vitro studies and in vivo experiments in mice indicated that TR-433 is nontoxic. TR-433 induced pro-inflammatory responses in THP-1 monocytes and HEK293T cells that were transiently transfected with TLR4/CD14/MD2 and also in BALB/c mice. In light of the self-assembly and pro-inflammatory properties of TR-433, we immunized with a mixture of TR-433 and either ovalbumin or filarial antigen trehalose-6-phosphate phosphatase (TPP). A significant amount of IgG titers was produced, suggesting adjuvanting capability of TR-433 that was comparable with that of Freund's complete adjuvant (FCA) and appreciably higher than that of alum. We found that TR-433 preferentially activates type 1 helper T cell (Th1) response rather than type 2 helper T cell (Th2) response. To our knowledge, this is the first report on the identification of a short TLR4-derived peptide that possesses both self-assembling and pro-inflammatory properties and has significant efficacy as an adjuvant, capable of activating cellular responses in mice. These results indicate that TR-433 possesses significant potential for development as a new adjuvant in therapeutic application.

Synthesis and study of benzofuran-pyran analogs as BMP-2 targeted osteogenic agents.

Twenty-four novel benzofuran-pyran derivatives were synthesized and evaluated for their anti-osteoporotic activity in primary cultures of rat calvarial osteoblasts in vitro. Among all the compounds screened for the alkaline phosphatase activity, three compounds 4e, 4j and 4k showed potent activity at picomolar concentrations in osteoblast differentiating stimulation. Additionally, these compounds were found effective in mineralization, assessed by alizarin red-S staining assay. Compounds were again validated through a series of other in vitro experiments. Moreover, molecular dynamics simulations demonstrated that both benzofuran and pyran moieties are requisite to fit into the active site of BMP-2 receptor, a key target of the osteogenic agents. The obtained results strongly convey that compound 4e is a potential bone anabolic agent among synthesized series, which can be further explored as a drug lead for treating osteoporosis.

In Situ Study to Confirm the Anticaries Potential of a Sodium Monofluorophosphate Dentifrice Containing Calcium Sodium Phosphosilicate.

OBJECTIVES: A randomized, investigator-blind, five-treatment, crossover, non-inferiority study was conducted to investigate the effect of the addition of calcium sodium phosphosilicate (CSPS), an agent known to relieve dentin hypersensitivity, to a sodium monofluorophosphate (SMFP)-containing dentifrice on the enamel remineralization potential of fluoride (F), as assessed by percentage surface microhardness recovery (%SMHR) and enamel fluoride uptake (EFU) using a standard in situ caries model. METHODS: Seventy-seven subjects wearing bilateral mandibular partial dentures holding partially demineralized bovine enamel specimens 24 hours/day brushed their teeth with their assigned randomized dentifrice containing either 1500 or 0 ppm F with 5% CSPS or 1500, 500, or 0 ppm F with 0% CSPS twice daily for 21 days. The success criterion was to observe a difference in % SMHR between dentifrices containing 1500 ppm F of six units or less in the upper bound of the two-sided 95% confidence interval (CI). RESULTS: Following 21 days of treatment, the upper bound CI of the %SMHR difference between the dentifrices containing 1500 ppm F was 1.66, thus within the non-inferiority limit. No statistically significant differences for %SMHR (p = 0.2601) and EFU (p = 0.2984) were noted between these two dentifrices. CONCLUSIONS: The present in situ caries study provides evidence demonstrating that the addition of the calcium-containing compound CSPS to a 1500 ppm F dentifrice does not interfere with the ability of fluoride to remineralize surface-softened enamel; i.e., CSPS neither impairs nor improves the potential cariostatic value of SMFP dentifrice.

Discovery of novel inhibitors for Leishmania nucleoside diphosphatase kinase (NDK) based on its structural and functional characterization.

Nucleoside diphosphate kinases (NDKs) are ubiquitous enzymes that catalyze the transfer of the γ-phosphate moiety from an NTP donor to an NDP acceptor, crucial for maintaining the cellular level of nucleoside triphosphates (NTPs). The inability of trypanosomatids to synthesize purines de novo and their dependence on the salvage pathway makes NDK an attractive target to develop drugs for the diseases they cause. Here we report the discovery of novel inhibitors for Leishmania NDK based on the structural and functional characterization of purified recombinant NDK from Leishmania amazonensis. Recombinant LaNDK possesses auto-phosphorylation, phosphotransferase and kinase activities with Histidine 117 playing an essential role. LaNDK crystals were grown by hanging drop vapour diffusion method in a solution containing 18% PEG-MME 500, 100 mM Bis-Tris propane pH 6.0 and 50 mM MgCl2. It belongs to the hexagonal space group P6322 with unit cell parameters a = b = 115.18, c = 62.18 Å and α = ß = 90°, γ = 120°. The structure solved by molecular replacement methods was refined to crystallographic R-factor and Rfree values of 22.54 and 26.52%, respectively. Molecular docking and dynamics simulation-based virtual screening identified putative binding compounds. Protein inhibition studies of selected hits identified five inhibitors effective at micromolar concentrations. One of the compounds showed ~45% inhibition of Leishmania promastigotes proliferation. Analysis of inhibitor-NDK complexes reveals the mode of their binding, facilitating design of new compounds for optimization of activities as drugs against leishmaniasis.

Association of core needle biopsy tract resection with local recurrence in extremity soft tissue sarcoma.

OBJECTIVE: Due to minimal tissue violation in percutaneous core needle biopsy (CNB), in contrast to open biopsy, the risk of tumor seeding and subsequent local recurrence (LR) along the biopsy tract remains unclear in extremity soft tissue sarcoma (STS). This study sought to examine the association of CNB tract resection on LR in a large STS institutional database. MATERIALS AND METHODS: After a retrospective review of the 116 patients who underwent CNB prior to surgery for previously untreated non-metastatic extremity STS, 36 patients who did not have CNB tracts resected (CNB-NR) were matched with 36 who had CNB tracts resected (CNB-R) for the factors that are known to affect LR. RESULTS: Two patients (6%) developed LR in the CNB-R group, whereas three patients (8%) developed LR in the CNB-NR group (P = 0.643). On Kaplan-Meier analysis, there was no significant difference in LR-free survival between the two groups (94.3% ± 3.9 for the CNB-R group vs. 93.8% ± 4.3 for the CNB-NR group, P = 0.747). CONCLUSION: Our data suggest any influence of a CNB tract resection on LR, within the limitations of this study, is likely to be of minor clinical importance in extremity STS. Although it would be prudent to resect the CNB tract in most cases, not resecting the CNB tract is a feasible option if identification or removal of the CNB tract proves difficult.

Additional synthesis on thiophene-containing trisubstituted methanes (TRSMs) as inhibitors of M. tuberculosis and 3D-QSAR studies.

We earlier reported thiophene-containing trisubstituted methanes (TRSMs) as novel cores carrying anti-tubercular activity, and identified S006-830 as the phenotypic lead with potent bactericidal activity against single- and multi-drug resistant clinical isolates of Mycobacterium tuberculosis (M. tb). In this work, we carried out additional synthesis of several TRSMs. The reaction scheme essentially followed the Grignard reaction and Friedel-Crafts alkylation, followed by insertion of a dialkylaminoethyl chain. We also performed microbiological evaluations including in vitro screening against the virulent strain M. tb H37Rv, cytotoxicity assessment in the Vero C-1008 cell line, and 3D-QSAR studies with comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). CoMFA and CoMSIA models yielded good statistical results in terms of q2 and r2 values, suggesting the validity of the models. It was concluded that a para-substituted benzene ring with bulkier electron-donating groups and aminoalkyl chains are required for higher inhibitory capacity against M. tuberculosis. We believe that these insights will rationally guide the design of newer, optimal, TRSMs.

Cross reactive molecules of human lymphatic filaria Brugia malayi inhibit Leishmania donovani infection in hamsters.

Coinfections are common in natural populations and the outcome of their interactions depends on the immune responses of the host elicited by the parasites. Earlier we showed that immunization with BmAFII (Sephadex G-200 eluted) fraction of human lymphatic filaria Brugia malayi inhibited progression of Leishmania donovani infection in golden hamsters. In the present study we identified cross reactive molecules of B. malayi, and investigated their effect on L. donovani infection and associated immune responses in the host. The sequence alignment and sharing of linear T- and B-cell epitopes in protein molecules of B. malayi and L. donovani counterparts were studied in silico. Hamsters were immunized with robustly cross reactive SDS-PAGE resolved fractions F6 (54.2-67.8kDa) and F9 (41.3-45.0kDa) of B. malayi and subsequently inoculated with amastigotes of L. donovani intracardially. F6 inhibited (∼72%) L. donovani infection and upregulated Th1 cytokine expression, lymphoproliferation, IgG2, IgG2/3 levels and NO production, and downregulated Th2 cytokine expression. Sequences in HSP60 and EF-2 of F6 and L. donovani counterparts were conserved and B- and T-cell epitopes in the proteins shared antigenic regions. In conclusion, leishmania-cross reactive molecules of filarial parasite considerably inhibited leishmanial infection via Th1-mediated immune responses and NO production. Common B- and T-cell epitope regions in HSP60 and EF-2 of the parasites might have contributed to the inhibitory effect on the L. donovani infection. Thus, leishmania-cross reactive filarial parasite molecules may help in designing prophylactic(s) against L. donovani.

Intra-operative cell salvage in cardiac surgery may increase platelet transfusion requirements: a cohort study.

BACKGROUND AND OBJECTIVES: The cell saver (CS) has been widely utilized in cardiac surgery to reduce red blood cell (RBC) transfusion. We aim at examining its effect on the rate of allogeneic transfusion, morbidity and mortality in our population. MATERIALS AND METHODS: Retrospective review of all patients operated at the Sultan Qaboos University Hospital between 2008 and 2013 was performed. Patients' demographics, comorbidities and surgical details were retrieved. Study end-points included blood transfusion, infection, renal failure and mortality. Baseline characteristics of both groups were compared and differences were adjusted for in the multivariable logistic regression. RESULTS: A total of 673 patients were included (CS = 395, non-CS = 278). Baseline characteristics were similar except for systemic hypertension, congestive heart failure and use of cardiopulmonary bypass. The CS group had higher transfusion rates of platelets (CS 36% vs. non-CS 18%; P < 0·001) and plasma (CS 31% vs. non-CS 19%; P < 0·001). After adjusting for baseline differences, CS use increased the odds of receiving platelet transfusion (odds ratio (OR) 3·2; P < 0·001) but not of plasma transfusion (OR 1·6; P = 0·087). There was no difference in the rate of RBC transfusion (CS 45% vs. non-CS 40%; P = 0·212), renal failure (CS 11% vs. non-CS 6%; P = 0·139), infection (CS 16% vs. non-CS 13%; P = 0·434) and mortality (CS 5% vs. non-CS 2%; P = 0·146). CONCLUSION: The CS use increases platelet requirements and has no impact on the rate of RBC transfusion in our population. These findings warrant caution with generalized use and require larger studies to confirm its results.