Simulation and Measurement of Aerosolisation in Different Chest Drainage Systems.

The aim of the study was to assess the degree of aerosolisation in different chest drainage systems according to different air leak volumes, in a simulated environment. This novel simulation model was designed to produce an air leak by passing air through and agitating a fluorescent fluid. The air leak volume and amount of fluorescent fluid were tested in various combinations and aerosolisation was assessed at 10-minute intervals using the ultraviolet light. The following chest drainage systems were compared: (1) single-chamber chest drainage system, (2) 3-compartment wet-dry suction chest drainage system, (3) digital drainage and monitoring system. The impact of suction (-2 and -4 kPa) in generating aerosolised particles was tested as well. A total number of 187 of 10-minute interval measurements were performed. The single-chamber chest drainage system generated the largest number of aerosolised particles at different air leak volumes and drainage output. The 3-compartment wet-dry suction system and the digital drainage and monitoring system did not generate any identifiable aerosolised particles at any of the air leak or drain output volumes considered. Suction applied to the chest drainage systems did not have an effect on aerosolisation. Aerosol generation in the simulated air-leak model demonstrated the potential risk of SARS-CoV-2 spread in the clinical setting. Full personal protective equipment must be used in patients with an air leak. Single-chamber chest drainage system generates the highest rate of aerosolised particles and it should not be used as an open system in patients with an air leak.

Ten-year improved survival in patients with multi-vessel coronary disease and poor left ventricular function following surgery: A retrospective cohort study.

OBJECTIVE: Patients with multi-vessel coronary artery disease and poor left ventricular (LV) function (ejection fraction [EF] < 30%) requiring revascularization are considered 'high-risk'. Limited long-term survival data exists comparing percutaneous coronary intervention (PCI) with second-generation drug-eluting stents (DES) versus surgery for this cohort of patients. METHODS: We retrospectively reviewed our data for 321 patients with EF < 30% who underwent multi-vessel revascularization from January 2005 to December 2015 using Cox regression analyses and inverse probability treatment weighted (IPTW) methods. We stratified patients that underwent surgical revascularization into on-pump coronary artery bypass grafting (CABG) and off-pump CABG and analyzed all-cause mortality at 10 years compared to PCI. RESULTS: 214 patients underwent CABG (n [on-pump CABG] = 94; n [off-pump CABG] = 120) and 107 patients had PCI with second generation DES. PCI with DES had higher 10-year mortality compared with on-pump CABG (Hazard ratio [HR] = 1.86, 95% confidence interval [CI] = 1.46-2.42; p < 0.001) and off-pump CABG (HR = 2.32, 95% CI = 1.75-3.15; p < 0.001). This was confirmed in IPTW analyses. When adjusting for both measured and unmeasured factors using instrumental variable analyses, PCI with DES had higher 10-year mortality compared with on-pump CABG (Δ = 13.5, 95% CI = 3.2-24.5; p = 0.012) and off-pump CABG (Δ = 16.1, 95% CI = 5.9-25.8; p < 0.001). CONCLUSION: Surgical revascularization, preferably off-pump CABG, results in better long-term survival compared with PCI using second generation DES for patients with multi-vessel coronary artery disease and poor left ventricular function. Randomized controlled trials in this patient group should be undertaken.

On-pump and off-pump coronary artery bypass grafting for patients needing at least two grafts: comparative outcomes at 20 years.

OBJECTIVES: Despite evidence from several randomized controlled trials and observational studies validating short-term safety and efficacy of off-pump coronary artery bypass grafting (CABG), concerns persist regarding the impact of off-pump CABG on long-term survival and freedom from reintervention. This persistent scepticism regarding off-pump CABG prompted us to review our practice of CABG over the last 20 years with a view to comparing the impact of off-pump and on-pump CABG on short-term and long-term outcomes in a high-volume off-pump coronary surgery centre. METHODS: We retrospectively analysed prospectively collected data from the Patients Analysis and Tracking System database (Dendrite Clinical Systems, Oxford, UK) for all isolated first-time CABG procedures with at least 2 grafts performed at our institution from January 1996 to September 2017. Over the study period, 5995 off-pump CABG and 4875 on-pump CABG were performed by surgeons with exclusive off-pump and on-pump practices, respectively. Multivariable logistic regression and the Cox model were used to investigate the effect of off-pump versus on-pump procedures on short-term outcomes and long-term survival. Propensity score matching was used to compare the 2 matched groups. RESULTS: Off-pump CABG was associated with a lower risk for 30-day mortality [odds ratio (OR) 0.42, 95% confidence interval (CI) 0.32-0.55; P < 0.001], reintubation/tracheostomy (OR 0.58, 95% CI 0.47-0.72; P < 0.001) and re-exploration for bleeding (OR 0.48, 95% CI 0.37-0.62; P < 0.001). The benefit in terms of operative deaths from off-pump was significant in those with Society of Cardio-Thoracic Surgery logistic EuroSCORE >2 (interaction P = 0.04). When compared with on-pump CABG, off-pump CABG did not significantly reduce the risk of stroke (OR 0.96, 95% CI 0.88-1.12; P = 0.20) and postoperative haemofiltration (OR 0.98, 95% CI 0.86-1.20; P = 0.35). At the median follow-up of 12 years (interquartile range 6-17, max 21), off-pump CABG did not affect late survival [log rank P = 0.24; hazard ratio (HR) 0.95, 95% CI 0.89-1.02] or the need for reintervention (log rank P = 0.12; HR 1.19, 95% CI 0.95-1.48). CONCLUSIONS: This large volume, single-centre study with the longest reported follow-up confirms that off-pump CABG performed by experienced surgeons, who perform only off-pump procedures in a high-volume off-pump coronary surgery centre, is associated with lower risk of operative deaths, fewer postoperative complications and similar 20-year survival and freedom from reintervention rates compared with on-pump CABG.

Immunological responses to a 39.8kDa Plasmodium vivax tryptophan-rich antigen (PvTRAg39.8) among humans.

Tryptophan-rich protein from P. yoelii called PypAg3 had shown protection in a murine model. We describe here its P. vivax orthologue named PvTRAg39.8 which is expressed during schizont stages of the parasite. The transcription initiation site was mapped to the -41 nucleotide position from the first AUG codon and thus established the ORF of PvTRAg39.8 which codes for a 322aa long protein. The sequence of this protein is highly conserved among the P. vivax isolates. Recombinant PvTRAg39.8 was expressed in E. coli, purified to electrophoretic homogeneity, and used for immunological studies. A majority of P. vivax-exposed individuals (90%, n=50) contained antibodies against the recombinant PvTRAg39.8. There was a switching of immunoglobulin isotypes against this antigen from IgG1 to IgG4 among individuals from the acute phase of P. vivax infection to convalescence. The PBMCs of 80% of the total 20 P. vivax-exposed individuals showed proliferation when stimulated with this antigen. The cytokine pattern produced by the PBMCs of the P. vivax-exposed individuals, after stimulation with this antigen, indicated a mixed type of immune response with a distinct bias towards the Th2 anti-inflammatory profile. Because of its high natural immunogenicity, conserved nature, and the protective properties of its P. yoelii counterpart, this protein may be a potential candidate for developing the immunotherapeutic reagents.

External aortic clamping versus endoaortic balloon occlusion in minimally invasive cardiac surgery: a systematic review and meta-analysis.

OBJECTIVES: Minimally invasive cardiac valve surgery is safe, effective and increasingly popular. It is performed worldwide with the use of either external aortic clamping or endoaortic balloon occlusion. METHODS: We conducted a literature search using MEDLINE, EMBASE, Scopus and Web of Science. Primary outcomes included aortic dissection, conversion to sternotomy, mortality, stroke and cross-clamp time. Secondary outcomes included atrial fibrillation, acute kidney injury, reoperation for bleeding, cardiopulmonary bypass times, myocardial infarction, use of intra-aortic balloon pump and length of hospital stay. The random effects model was used to calculate the outcomes of both binary and continuous data. RESULTS: Thirty retrospective studies were included in the meta-analysis. The incidence of aortic dissection (pooled odds ratio = 3.88, 95% confidence interval = 1.06-14.18; P =0.04) and conversion to sternotomy (pooled odds ratio = 3.07, 95% confidence interval = 1.33-7.10; P = 0.009) was higher in the endoaortic balloon occlusion group than in the external aortic clamping group, in whom a direct comparison was possible. The remaining observational studies did not show any significant differences in either group. There was no significant difference in 30-day mortality (P = 0.37), stroke (P = 0.26), cross-clamp time (P = 0.20), atrial fibrillation (P = 0.18), acute kidney injury (P = 0.49), reoperation for bleeding (P = 0.24), cardiopulmonary bypass time (P = 0.06), myocardial infarction (P = 0.74), use of intra-aortic balloon pump (P = 0.11) or length of hospital stay (P = 0.47). CONCLUSIONS: External aortic clamping may be safer than endoaortic balloon occlusion with respect to aortic dissection and conversion to sternotomy. However, mortality, length of stay, stroke, cross-clamp time and other cardiovascular complication rates were similar between the 2 techniques.

Comparison of minimally invasive direct coronary artery bypass and drug-eluting stents for management of isolated left anterior descending artery disease: a systematic review and meta-analysis of 7,710 patients.

BACKGROUND: In the contemporary era of drug-eluting stents (DES) the issue of optimal revascularization strategy for patients with isolated disease of the left anterior descending (LAD) artery has gained more significance. We aimed to evaluate the current best evidence on the subject by performing a systematic review and meta-analysis of the studies comparing minimally invasive direct coronary artery bypass (MIDCAB) grafting with DES in patients with isolated LAD disease. METHODS: A literature search was conducted from 1966 through March 2018 using MEDLINE, EMBASE, and other scientific databases to identify relevant articles. Analyzed outcomes included all-cause mortality, myocardial infarction (MI), major adverse cardiac and cerebrovascular events (MACCE) and target vessel revascularization (TVR). The random effects model was used to calculate the outcomes of both binary and continuous data to control any heterogeneity between the studies. Heterogeneity amongst the trials was determined by means of the Cochran Q value and quantified using the I2 inconsistency test. All P values were 2-sided and a 5% level was considered significant. RESULTS: A total of 7,710 patients from 12 studies were identified. There was no significant difference in mortality rate [pooled odds ratio (OR) =0.92; 95% confidence interval (CI), 0.65 to 1.32; P=0.66], MI rate (pooled OR =1.13, 95% CI, 0.62 to 2.06; P=0.69) or MACCE (pooled OR =1.31; 95% CI, 0.58 to 2.95; P=0.52). However, TVR rate was significantly more for patients having percutaneous intervention with DES (pooled OR =0.27; 95% CI, 0.16 to 0.45; P<0.0001) compared to MIDCAB. CONCLUSIONS: MIDCAB offers superior freedom from TVR with similar mortality, MI rate, and MACCE compared to percutaneous intervention with DES for revascularization in patient with isolated proximal LAD stenosis.

Short-term clinical outcomes and long-term survival of minimally invasive direct coronary artery bypass grafting.

BACKGROUND: Minimally invasive direct coronary artery bypass (MIDCAB) grafting is regarded as an alternative to conventional coronary artery bypass grafting (CABG) through full sternotomy, particularly for patients with isolated proximal left anterior descending (LAD) artery stenosis deemed unsuitable for percutaneous coronary intervention. However, the technically demanding nature of the procedure and lack of long-term published outcomes have precluded its universal adoption. We report the comparative short-term outcomes and long-term survival of MIDCAB and conventional CABG through full sternotomy for grafting of isolated LAD. METHODS: From February 1996 to October 2017, a total of 668 patients underwent MIDCAB (n=508) and full sternotomy (n=160) CABG for isolated proximal LAD stenosis. Their data were prospectively entered into the institutional cardiac surgery database (Patients Analysis & Tracking System; Dendrite Clinical Systems, Ltd, Oxford, England, United Kingdom) and analyzed retrospectively. Information on patient deaths was obtained from the institutional database and the National General Register Office for all patients. RESULTS: The two groups were comparable with respect to preoperative demographics and risk profile. MIDCAB was associated with longer operative time (177±32 versus 141±12 min; P=0.003). The two groups did not significantly differ with regard to other complications including operative mortality. At a mean follow-up of 12.95±0.47 years, survival was also similar. CONCLUSIONS: This large single centre study with longest follow-up validates the status of MIDCAB as an effective strategy for grafting of LAD. However, it fails to show superiority of the minimally invasive approach compared to conventional CABG through full sternotomy.

Sequence diversity and natural selection at domain I of the apical membrane antigen 1 among Indian Plasmodium falciparum populations.

BACKGROUND: The Plasmodium falciparum apical membrane antigen 1 (AMA1) is a leading malaria vaccine candidate antigen. The complete AMA1 protein is comprised of three domains where domain I exhibits high sequence polymorphism and is thus named as the hyper-variable region (HVR). The present study describes the extent of genetic polymorphism and natural selection at domain I of the ama1 gene among Indian P. falciparum isolates. METHODS: The part of the ama1 gene covering domain I was PCR amplified and sequenced from 157 P. falciparum isolates collected from five different geographical regions of India. Statistical and phylogenetic analyses of the sequences were done using DnaSP ver. 4. 10. 9 and MEGA version 3.0 packages. RESULTS: A total of 57 AMA1 haplotypes were observed among 157 isolates sequenced. Forty-six of these 57 haplotypes are being reported here for the first time. The parasites collected from the high malaria transmission areas (Assam, Orissa, and Andaman and Nicobar Islands) showed more haplotypes (H) and nucleotide diversity pi as compared to low malaria transmission areas (Uttar Pradesh and Goa). The comparison of all five Indian P. falciparum subpopulations indicated moderate level of genetic differentiation and limited gene flow (Fixation index ranging from 0.048 to 0.13) between populations. The difference between rates of non-synonymous and synonymous mutations, Tajima's D and McDonald-Kreitman test statistics suggested that the diversity at domain I of the AMA1 antigen is due to positive natural selection. The minimum recombination events were also high indicating the possible role of recombination in generating AMA1 allelic diversity. CONCLUSION: The level of genetic diversity and diversifying selection were higher in Assam, Orissa, and Andaman and Nicobar Islands populations as compared to Uttar Pradesh and Goa. The amounts of gene flow among these populations were moderate. The data reported here will be valuable for the development of AMA1-based malaria vaccine.

Plasmodium vivax tryptophan-rich antigen PvTRAg33.5 contains alpha helical structure and multidomain architecture.

Tryptophan-rich proteins from several malarial parasites have been identified where they play an important role in host-parasite interaction. Structural characterization of these proteins is needed to develop them as therapeutic targets. Here, we describe a novel Plasmodium vivax tryptophan-rich protein named PvTRAg33.5. It is expressed by blood stage(s) of the parasite and its gene contains two exons. The exon 1 encodes for a 23 amino acids long putative signal peptide which is likely to be cleaved off whereas the exon 2 encodes for the mature protein of 252 amino acids. The mature protein contains B-cell epitopes which were recognized by the human immune system during P.vivax infection. The PvTRAg33.5 contains 24 (9.5%) tryptophan residues and six motifs whose patterns were similar among tryptophan-rich proteins. The modeled structure of the PvTRAg33.5 consists of a multidomain architecture which is stabilized by the presence of large number of tryptophan residues. The recombinant PvTRAg33.5 showed predominantly α helical structure and alpha helix to beta sheet transition at pH below 4.5. Protein acquires an irreversible non-native state at temperature more than 50°C at neutral pH. Its secondary and tertiary structures remain stable in the presence of 35% alcohol but these structures are destabilized at higher alcohol concentrations due to the disturbance of hydrophobic interactions between tryptophanyl residues. These structural changes in the protein might occur during its translocation to interact with other proteins at its final destination for biological function such as erythrocyte invasion.