Mid-term outcomes for Endoscopic versus Open Vein Harvest: a case control study

<p>Abstract</p> <p>Background</p> <p>Saphenous vein remains the most common conduit for coronary artery bypass grafting with increasing uptake of minimally invasive harvesting techniques. While Endoscopic Vein Harvest (EVH) has been demonstrated to improve early morbidity compared to Open Vein Harvest (OVH), recent literature suggests that this may be at the expense of graft patency at one year and survival at three years.</p> <p>Methods</p> <p>We undertook a retrospective single-centre, single-surgeon, case-control study of EVH (n = 89) and OVH (n = 182). The primary endpoint was death with secondary endpoints including acute coronary syndrome, revascularisation or other major adverse cardiac events. Freedom from angina, wound complications and self-rated health status were also assessed. Where repeat angiography had been performed, this was reviewed.</p> <p>Results</p> <p>Both groups were well matched demographically and for peri-operative characteristics. All cause mortality was 2/89 (2%) and 11/182 (6%) in the EVH and OVH groups respectively. This was shown by Cox Log-Rank analysis to be non-significant (p = 0.65), even if adjusting for inpatient mortality (p = 0.74). There was no difference in the rates of freedom from angina (p = 1.00), re-admission (p = 0.78) or need for further anti-anginals (p = 1.00). There was a significant reduction in the incidence of leg wound infections and complications in the endoscopic group (EVH: 7%; OVH: 28%; p = 0.0008) and the skew of high patient self-rated health scores in the EVH group (61% compared to 52% in the open group) approached statistical significance (p = 0.06).</p> <p>Conclusions</p> <p>While aware of the limitations of this small retrospective study, we are heartened by the preliminary results and consider our data to be justification for continuing to provide patients the opportunity to have minimally invasive conduit harvest in our centre. More robust evidence is still required to elucidate the implications of endoscopic techniques on conduit patency and patient outcome, but until the results of a large, prospective and randomised trial are available, we believe we can confidently offer our patients the option and benefits of EVH.</p

ABCC Multidrug Transporters in Childhood Neuroblastoma: Clinical and Biological Effects Independent of Cytotoxic Drug Efflux

Background Although the prognostic value of the ATP-binding cassette, subfamily C (ABCC) transporters in childhood neuroblastoma is usually attributed to their role in cytotoxic drug efflux, certain observations have suggested that these multidrug transporters might contribute to the malignant phenotype independent of cytotoxic drug efflux. Methods A v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (MYCN)-driven transgenic mouse neuroblastoma model was crossed with an Abcc1-deficient mouse strain (658 hMYCN1/−, 205 hMYCN+/1 mice) or, alternatively, treated with the ABCC1 inhibitor, Reversan (n = 20). ABCC genes were suppressed using short interfering RNA or overexpressed by stable transfection in neuroblastoma cell lines BE(2)-C, SH-EP, and SH-SY5Y, which were then assessed for wound closure ability, clonogenic capacity, morphological differentiation, and cell growth. Real-time quantitative polymerase chain reaction was used to examine the clinical significance of ABCC family gene expression in a large prospectively accrued cohort of patients (n = 209) with primary neuroblastomas. Kaplan-Meier survival analysis and Cox regression were used to test for associations with event-free and overall survival. Except where noted, all statistical tests were two-sided. Results Inhibition of ABCC1 statistically significantly inhibited neuroblastoma development in hMYCN transgenic mice (mean age for palpable tumor: treated mice, 47.2 days; control mice, 41.9 days; hazard ratio [HR] = 9.3, 95% confidence interval [CI] = 2.65 to 32; P < .001). Suppression of ABCC1 in vitro inhibited wound closure (P < .001) and clonogenicity (P = .006); suppression of ABCC4 enhanced morphological differentiation (P < .001) and inhibited cell growth (P < .001). Analysis of 209 neuroblastoma patient tumors revealed that, in contrast with ABCC1 and ABCC4, low rather than high ABCC3 expression was associated with reduced event-free survival (HR of recurrence or death = 2.4, 95% CI = 1.4 to 4.2; P = .001), with 23 of 53 patients with low ABCC3 expression experiencing recurrence or death compared with 31 of 155 patients with high ABCC3. Moreover, overexpression of ABCC3 in vitro inhibited neuroblastoma cell migration (P < .001) and clonogenicity (P = .03). The combined expression of ABCC1, ABCC3, and ABCC4 was associated with patients having an adverse event, such that of the 12 patients with the "poor prognosis” expression pattern, 10 experienced recurrence or death (HR of recurrence or death = 12.3, 95% CI = 6 to 27; P < .001). Conclusion ABCC transporters can affect neuroblastoma biology independently of their role in chemotherapeutic drug efflux, enhancing their potential as targets for therapeutic interventio

Is Sustained Virological Response a Marker of Treatment Efficacy in Patients with Chronic Hepatitis C Viral Infection with No Response or Relapse to Previous Antiviral Intervention?

Background: Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs.  Methods: We created a decision tree model based on a Cochrane systematic review on interferon retreatment for patients who did not respond to initial therapy or who relapsed following SVR. Extrapolating data to 20 years, we modelled the outcome from three scenarios: (1) observed medium-term (5 year) annual mortality rates continue to the long term (20 years); (2) long-term annual mortality in retreatment responders falls to that of the general population while retreatment non-responders continue at the medium-term mortality; (3) long-term annual mortality in retreatment non-responders is the same as control group non-responders (i.e., the increased treatment-related medium mortality “wears off”).  Results: The mean differences in life expectancy over 20 years with interferon versus control in the first, second, and third scenarios were -0.34 years (95% confidence interval (CI) -0.71 to 0.03), -0.23 years (95% CI -0.69 to 0.24), and -0.01 (95% CI -0.3 to 0.27), respectively. The life expectancy was always lower in the interferon group than in the control group in scenario 1. In scenario 3, the interferon group had a longer life expectancy than the control group only when more than 7% in the interferon group achieved SVR.  Conclusions: SVR may be a good prognostic marker but does not seem to be a valid surrogate marker for assessing HCV treatment efficacy of interferon retreatment. The SVR threshold at which retreatment increases life expectancy may be different for different drugs depending upon the adverse event profile and treatment efficacy. This has to be determined for each drug by RCTs and appropriate modelling before SVR can be accepted as a surrogate marker

Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial

Importance: The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive. Objective: To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. Design, Setting, and Participants: The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. Interventions: The immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). Main Outcomes and Measures: The primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, -1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority &gt;99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility &gt;95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. Results: Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (O

The reflares and outburst evolution in the accreting millisecond pulsar SAX J1808.4-3658: A disk truncated near co-rotation?

© 2016. The American Astronomical Society. All rights reserved. The accreting millisecond X-ray pulsar SAX J1808.43658 shows peculiar low luminosity states known as "reflares" after the end of the main outburst. During this phase the X-ray luminosity of the source varies by up to three orders of magnitude in less than 12 days. The lowest X-ray luminosity observed reaches a value of ~1032 erg s-1, only a factor of a few brighter than its typical quiescent level. We investigate the 2008 and 2005 reflaring state of SAX J1808.43658 to determine whether there is any evidence for a change in the accretion flow with respect to the main outburst. We perform a multiwavelength photometric and spectral study of the 2005 and 2008 reflares with data collected during an observational campaign covering the near-infrared, optical, ultra-violet and X-ray band. We find that the NIR/optical/UV emission, expected to come from the outer accretion disk, shows variations in luminosity over an order of magnitude. The corresponding X-ray luminosity variations are instead much deeper, spanning about 23 orders of magnitude. The X-ray spectral state observed during the reflares does not change substantially with X-ray luminosity, indicating a rather stable configuration of the accretion flow. We investigate the most likely configuration of the innermost regions of the accretion flow and we infer an accretion disk truncated at or near the co-rotation radius. We interpret these findings as due to either a strong outflow (due to a propeller effect) or a trapped disk (with limited/no outflow) in the inner regions of the accretion flow

Methodology of calculation of construction and hydrodynamic parameters of a foam layer apparatus for mass-transfer processes

Промислова реалізація методу стабілізації газорідинного шару дозволяє значно розширити галузь застосування пінних апаратів і відкриває нові можливості інтенсифікації технологічних процесів з одночасним створенням маловідходних технологій. У статті встановлені основні параметри, що впливають на гідродинаміку пінних апаратів, розглянуті основні конструкції та режими роботи пінних апаратів. Виявлено зв'язок гідродинамічних параметрів. Розглянуто гідродинамічні закономірності пінного шару. Вказані фактори, що впливають на процес масообміну, як в газовій, так і в рідкій фазах. Проведений аналіз ряду досліджень показав, що перспективним напрямком інтенсифікації процесу масообміну є розробка апаратів з трифазним псевдозрідженим шаром зрошуваної насадки складних форм із сітчастих матеріалів. Отже, необхідне проведення спеціальних досліджень гідродинамічних режимів роботи апарату з сітчастою насадкою і визначенням параметрів, що впливають на швидкість переходу насадки з одного режиму в інший.Industrial implementation of the stabilization method of the gas-liquid layer can significantly expand the field of use of foaming apparatus and opens up new opportunities for intensifying technological processes with the simultaneous creation of low-waste technologies. The article establishes the basic parameters influencing the hydrodynamics of foam apparatus, considers the basic constructions and operating modes of foam apparatus. The connection of hydrodynamic parameters is revealed. The hydrodynamic laws of the foam layer are considered. The indicated factors affecting the process of mass transfer, both in the gas and in the liquid phases. The conducted analysis of a number of studies showed that the perspective direction of intensification of the mass transfer process is the development of apparatuses with a three-phase fluidized bed of an irrigated nozzle of complex forms with mesh materials

Germline mismatch repair (MMR) gene analyses from English NHS regional molecular genomics laboratories 1996–2020: development of a national resource of patient-level genomics laboratory records

Objective To describe national patterns of National Health Service (NHS) analysis of mismatch repair (MMR) genes in England using individual-level data submitted to the National Disease Registration Service (NDRS) by the NHS regional molecular genetics laboratories. Design Laboratories submitted individual-level patient data to NDRS against a prescribed data model, including (1) patient identifiers, (2) test episode data, (3) per-gene results and (4) detected sequence variants. Individualised per-laboratory algorithms were designed and applied in NDRS to extract and map the data to the common data model. Laboratory-level MMR activity audit data from the Clinical Molecular Genetics Society/Association of Clinical Genomic Science were used to assess early years’ missing data. Results Individual-level data from patients undergoing NHS MMR germline genetic testing were submitted from all 13 English laboratories performing MMR analyses, comprising in total 16 722 patients (9649 full-gene, 7073 targeted), with the earliest submission from 2000. The NDRS dataset is estimated to comprise >60% of NHS MMR analyses performed since inception of NHS MMR analysis, with complete national data for full-gene analyses for 2016 onwards. Out of 9649 full-gene tests, 2724 had an abnormal result, approximately 70% of which were (likely) pathogenic. Data linkage to the National Cancer Registry demonstrated colorectal cancer was the most frequent cancer type in which full-gene analysis was performed. Conclusion The NDRS MMR dataset is a unique national pan-laboratory amalgamation of individual-level clinical and genomic patient data with pseudonymised identifiers enabling linkage to other national datasets. This growing resource will enable longitudinal research and can form the basis of a live national genomic disease registry. Data availability statement Data are available upon reasonable request. Data may be obtained from a third party and are not publicly available. All data relevant to the study are included in the article or uploaded as supplementary information. All summary data relevant to the study are included in the article or uploaded as online supplementary information. Individual level data detailed in this study are held within NHS Digital with access available on application