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Right Ventricular Dysfunction and Its Association With Mortality in Coronavirus Disease 2019 Acute Respiratory Distress Syndrome.
No full textOBJECTIVES
To assess whether right ventricular dilation or systolic impairment is associated with mortality and/or disease severity in invasively ventilated patients with coronavirus disease 2019 acute respiratory distress syndrome.
DESIGN
Retrospective cohort study.
SETTING
Single-center U.K. ICU.
PATIENTS
Patients with coronavirus disease 2019 acute respiratory distress syndrome undergoing invasive mechanical ventilation that received a transthoracic echocardiogram between March and December 2020.
INTERVENTION
None.
MEASUREMENTS AND MAIN RESULTS
Right ventricular dilation was defined as right ventricular:left ventricular end-diastolic area greater than 0.6, right ventricular systolic impairment as fractional area change less than 35%, or tricuspid annular plane systolic excursion less than 17 mm. One hundred seventy-two patients were included, 59 years old (interquartile range, 49-67), with mostly moderate acute respiratory distress syndrome (n = 101; 59%). Ninety-day mortality was 41% (n = 70): 49% in patients with right ventricular dilation, 53% in right ventricular systolic impairment, and 72% in right ventricular dilation with systolic impairment. The right ventricular dilation with systolic impairment phenotype was independently associated with mortality (odds ratio, 3.11 [95% CI, 1.15-7.60]), but either disease state alone was not. Right ventricular fractional area change correlated with PaO2:FIO2 ratio, PaCO2, chest radiograph opacification, and dynamic compliance, whereas right ventricular:left ventricle end-diastolic area correlated negatively with urine output.
CONCLUSIONS
Right ventricular systolic impairment correlated with pulmonary pathophysiology, whereas right ventricular dilation correlated with renal dysfunction. Right ventricular dilation with systolic impairment was the only right ventricular phenotype that was independently associated with mortality
NFnetFu: A novel workflow for microbiome data fusion.
No full textMicrobiome data analysis and its interpretation into meaningful biological insights remain very challenging for numerous reasons, perhaps most prominently, due to the need to account for multiple factors, including collinearity, sparsity (excessive zeros) and effect size, that the complex experimental workflow and subsequent downstream data analysis require. Moreover, a meaningful microbiome data analysis necessitates the development of interpretable models that incorporate inferences across available data as well as background biomedical knowledge. We developed a multimodal framework that considers sparsity (excessive zeros), lower effect size, intrinsically microbial correlations, i.e., collinearity, as well as background biomedical knowledge in the form of a cluster-infused enriched network architecture. Finally, our framework also provides a candidate taxa/Operational Taxonomic Unit (OTU) that can be targeted for future validation experiments. We have developed a tool, the term NFnetFU (Neuro Fuzzy network Fusion), that encompasses our framework and have made it freely available at https://github.com/VartikaBisht6197/NFnetFu
Rectus sheath catheter analgesia versus standard care following major abdominal surgery: An observational study of 911 patients.
No full textBACKGROUND
It is unknown whether rectus sheath catheter (RSC) continuous infusion of local anaesthetic is superior to standard post-operative opiate analgesia following major abdominal surgery. Previous audit in our Trust had suggested RSC was very effective and reduced opiate analgesia use. We aimed to see if this was maintained as the technique became more widespread comparing clinical outcomes and post-operative opiate analgesia requirements between patients who had RSCs and those that did not following major abdominal surgery over a 32-month period.
METHODS
A retrospective observational study investigated patients who had major abdominal surgery at a single centre in the UK between January 2018 and August 2020. Placement of RSCs was at the discretion of the surgical team according to their own personal choice. All patients having the procedure in both an elective and non-elective setting have been included in this study, including patients requiring higher level care after emergency surgery. Clinical outcomes and post-operative opiate analgesia requirements (oral and intravenous) were analysed using multivariate logistic regression models adjusting for American Association of Anesthesiologists (ASA) grade and type of surgery (emergency vs elective and open vs laparoscopic).
RESULTS
There were 911 patients; 276/911 (30.3%) RSC and 635/911 (69.7%) non-RSC. Median age was 64 (52-74) years; 51.6% were male. In the adjusted models, RSC was associated with a reduced likelihood of serious complications (OR 0.49 (95% CI 0.33, 0.72); p < 0.001) and lower length of stay in ICU (OR 0.95 (95% CI 0.91, 0.99); p = 0.029). RSC was not associated with reduced post-operative opiate analgesia use. There were 3/276 (1.1%) adverse events following RSC placement during the period of data collection.
CONCLUSIONS
Clinical outcomes may be superior for patients following major abdominal surgery when RSCs are placed for post-operative analgesia but uncertainty remains. This paper highlights the difficulty with retrospective non-selected data in answering this question. High quality prospective randomised data are required to determine the effects on clinical outcomes and post-operative opiate analgesia requirements
Prognostic value of coronary risk factors, exercise capacity and single photon emission computed tomography in liver transplantation candidates: A 5-year follow-up study.
No full textBACKGROUND
Although consensus-based guidelines support noninvasive stress testing prior to orthotopic liver transplantation (OLT), the optimal screening strategy for assessment of coronary artery disease in patients with end-stage liver disease (ESLD) is unclear. This study sought to determine the relative predictive value of coronary risk factors, functional capacity, and single photon emission computed tomography (SPECT) on major adverse cardiovascular events and all-cause mortality in liver transplantation candidates.
METHODS
Prior to listing for transplantation, 404 consecutive ESLD patients were referred to a University hospital for cardiovascular (CV) risk stratification. All subjects met at least one of the following criteria: inability to perform > 4 METs by history (62%), insulin-treated diabetes mellitus (53%), serum creatinine > 1.72 mg/dL (8%), history of MI, PCI or CABG (5%), stable angina (3%), cerebrovascular disease (1%), peripheral vascular disease (1%). Subjects underwent Technetium-99m SPECT with multislice coronary artery calcium scoring (CACS) using exercise treadmill or standard adenosine stress in those unable to achieve 85% maximal heart rate (Siemens Symbia T16). Abnormal perfusion was defined as a summed stress score (SSS) ≥ 4.
RESULTS
Of the 404 patients, 158 (age 59 ± 9 years; male 68%) subsequently underwent transplantation and were included in the primary analysis. Of those, 50 (32%) died after a mean duration follow-up of 5.4 years (maximal 10.9 years). Most deaths (78%) were attributed to noncardiovascular causes (malignancy, sepsis, renal failure). Of the 32 subjects with abnormal perfusion (20%), nine (6%) had a high-risk perfusion abnormality defined as a total perfusion defect size (PDS) ≥ 15% and/or an ischemic PDS ≥ 10%. Kaplan-Meier survival curves demonstrated abnormal perfusion was associated with increased CV mortality (generalized Wilcoxon, P = 0.014) but not all-cause death. Subjects with both abnormal perfusion and an inability to exercise > 4 METs had the lowest survival from all-cause death (P = 0.038). Abnormal perfusion was a strong independent predictor of CV death (adjusted HR 4.2; 95% CI 1.4 to 12.3; P = 0.019) and MACE (adjusted HR 7.7; 95% CI 1.4 to 42.4; P = 0.018) in a multivariate Cox regression model that included age, sex, diabetes, smoking and the ability to exercise > 4 METs. There was no association between CACS and the extent of perfusion abnormality, nor with outcomes.
CONCLUSIONS
Most deaths following OLT are noncardiovascular. Nonetheless, abnormal perfusion is prevalent in this high-risk population and a stronger predictor of cardiovascular morbidity and mortality than functional status. A combined assessment of functional status and myocardial perfusion identifies those at highest risk of all-cause death. (Exercise Capacity and Single Photon Emission Computed Tomography in Liver Transplantation Candidates [ExSPECT]; ClinicalTrials.gov Identifier: NCT03864497)
Vitamin A deficiency: experience from a tertiary referral UK hospital; not just a low- and middle-income country issue.
No full textOBJECTIVE
Vitamin A (VA) deficiency, more common in low- and middle-income countries (LMIC) secondary to malnutrition, is associated with increased morbidity and mortality. The prevalence and impact of VA deficiency in high-income countries (HIC) where chronic conditions may predispose is less well understood.
DESIGN
Interpretation of serum retinol may be affected by inflammation, so C-reactive protein (CRP) levels were sought. Binary logistic regression and generalised estimating equations were performed to review the relationship between CRP and VA.
SETTING
We examined the scale of low and deficient VA status in our tertiary University Teaching Hospital (HIC).
PARTICIPANTS
Patients undergoing serum retinol concentrations 2012-2016 were identified from laboratory records, and records examined.
RESULTS
Totally, 628 assays were requested, with eighty-two patients VA low (0·7-0·99 Umol/l) or deficient (<0·7 Umol/l). Sixteen patients were symptomatic (fifteen deficient), predominantly visual. Only one symptomatic patient's VA deficiency was secondary to poor intake. Other symptomatic patients had chronic illnesses resulting in malabsorption. The incidence of a low VA level increases significantly with a raised CRP.
CONCLUSION
The majority of patients tested either were replete or likely to have abnormal VA levels due to concomitant inflammation. A minority of patients had signs and symptoms of VA deficiency and was a cause of significant morbidity, but aetiology differs from LMIC, overwhelmingly malabsorption, most commonly secondary to surgery or hepatobiliary disease. A correlation between inflammation and low VA levels exists, which raises the possibility that requesting a VA level in an asymptomatic patient with active inflammation may be of questionable benefit
Mortality from esophagectomy for esophageal cancer across low, middle, and high-income countries: An international cohort study.
No full textBACKGROUND
No evidence currently exists characterising global outcomes following major cancer surgery, including esophageal cancer. Therefore, this study aimed to characterise impact of high income countries (HIC) versus low and middle income countries (LMIC) on the outcomes following esophagectomy for esophageal cancer.
METHOD
This international multi-center prospective study across 137 hospitals in 41 countries included patients who underwent an esophagectomy for esophageal cancer, with 90-day follow-up. The main explanatory variable was country income, defined according to the World Bank Data classification. The primary outcome was 90-day postoperative mortality, and secondary outcomes were composite leaks (anastomotic leak or conduit necrosis) and major complications (Clavien-Dindo Grade III - V). Multivariable generalized estimating equation models were used to produce adjusted odds ratios (ORs) and 95% confidence intervals (CI).
RESULTS
Between April 2018 to December 2018, 2247 patients were included. Patients from HIC were more significantly older, with higher ASA grade, and more advanced tumors. Patients from LMIC had almost three-fold increase in 90-day mortality, compared to HIC (9.4% vs 3.7%, p < 0.001). On adjusted analysis, LMIC were independently associated with higher 90-day mortality (OR: 2.31, CI: 1.17-4.55, p = 0.015). However, LMIC were not independently associated with higher rates of anastomotic leaks (OR: 1.06, CI: 0.57-1.99, p = 0.9) or major complications (OR: 0.85, CI: 0.54-1.32, p = 0.5), compared to HIC.
CONCLUSION
Resections in LMIC were independently associated with higher 90-day postoperative mortality, likely reflecting a failure to rescue of these patients following esophagectomy, despite similar composite anastomotic leaks and major complication rates to HIC. These findings warrant further research, to identify potential issues and solutions to improve global outcomes following esophagectomy for cancer
Raman spectroscopy accurately differentiates mucosal healing from non-healing and biochemical changes following biological therapy in inflammatory bowel disease.
No full textBACKGROUND
Mucosal healing (MH) is a key treatment target in the management of inflammatory bowel disease (IBD) and is defined in endoscopic terms by the newly published PICaSSO score. Raman Spectroscopy (RS) is based on the scattering of inelastic light giving spectra that are highly specific for individual molecules. We aimed to establish spectral changes before and after treatment and whether Raman Spectroscopy is able to accurately differentiate between inflammation and MH.
METHODS
Biopsies were taken for ex vivo RS analysis alongside biopsies for histological analysis from IBD patients undergoing optical diagnosis endoscopic assessment. We compared pre- vs. post-biological treatment in IBD patients and healthy controls and active vs. MH in UC and CD. For spectral analysis, we used supervised self-organising maps for separation and classification.
RESULTS
A total of 23 patients (14 IBD, 9 HC) were recruited for comparison of pre- vs. post-biologic treatment and 74 IBD patients were included for the assessment of MH in IBD, giving 9700 Raman Spectra. Spectral differences were seen between pre- and post-treatment which were observed comparing MH vs. active inflammation. Reductions in intensity at 1003cm-1 and 1252cm-1 when a reduction in inflammation was seen post-treatment and when MH was present. MH was associated with an increase in intensity at 1304cm-1. The trained neural network differentiated MH from active inflammation with a sensitivity, specificity, PPV, NPV and accuracy in UC of 96.29% (sd 0.94), 95.03% (sd 1.52), 94.89% (sd 1.59), 96.33 (sd 0.97) and 95.65 (sd 0.99) and 96.19% (sd 1.46), 88% (sd 4.20), 86.60% (sd 5.39), 96.55% (sd 1.32) and 91.6% (sd 2.75) in CD respectively.
CONCLUSION
We demonstrated RS can demonstrate biochemical changes following treatment of IBD and accurately differentiates MH from active inflammation in IBD and might be a future tool to personalise therapeutic management in IBD
Monteggia Variant with Salter-Harris Fracture of the Radial Head: Case Report and Litergature Review.
No full textIntroduction
The Monteggia fracture is a fracture to the proximal third of ulna associated with a radial head dislocation. Although this is well described and classified in adults, it is uncommon in children. Identifying growth plate trauma and subsequent surgical management are of critical importance. This report identifies a unique variant of Monteggia fracture with a Salter-Harris Type I injury of the radial head instead of a dislocation, and how it was successfully stabilised with a closed reduction.
Case Rport
We present a case of a nine 9 year-old female admitted to our unit with a deformed upper extremity following a fall from height. This was a closed and isolated injury without neurovascular compromise. Radiographs revealed a displaced fracture to the proximal ulna shaft. Unlike a true Monteggia, the radial fracture went through the proximal physis with anterior divergence of the distal fragment. The radiocapitellar joint remained congruent. The ulna fracture was stabilized with open reduction and plate osteosynthesis whilst the radial injury underwent closed reduction and intramedullary pinning with excellent outcomes and maintenance of full range of motion.
Conclusion
This case highlights a new variant and successful outcome following a closed reduction intramedullary fixation technique in this emergent pattern of injury. We highlight the need for a classification of these fractures in children
Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine.
No full textExtension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T cell response to the spike protein. NAb levels were higher after the extended dosing interval (6-14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4 T cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol
Cessation of ambulation results in a dramatic loss of trabecular bone density in boys with Duchenne muscular dystrophy (DMD).
No full textGlucocorticoids are currently used to improve muscle strength and prolong ambulation in boys with DMD although the effect on bone health is still unclear. The aim of this study was to compare bone strength in healthy children and boys with DMD and investigate the interaction between diminished muscle function, loss of ambulation and high dose oral steroids, over a two year time frame. Fifty children were studied, 14 healthy boys (HB), 13 boys with DMD who remained ambulant (DMD-RA) and 23 boys with DMD who lost ambulation (DMD-LA). All boys with DMD had taken oral glucocorticoids. Peripheral quantitative computed tomography was used to measure bone geometry, density, strength and muscle mass of the non-dominant tibia and radius. Measurements were made at baseline, 12 and 24 months at the distal metaphysis and mid diaphysis sites. Differences between the three groups were evaluated using ANOVA and a repeated measures model. There were no significant differences in age between the groups: mean age was 9.4, 8.7 and 8.8 years for HB, DMD-RA and DMD-LA, respectively. There was no significant difference in steroid exposure between the DMD groups. However, boys who lost ambulation had significantly lower muscle function at baseline (North Star Ambulatory Assessment DMD-RA 23.6 vs. DMD-LA 18.8; p < 0.05). At baseline, healthy boys had significantly greater trabecular bone density at the distal radius /ulna (23%/27%) and distal tibia/fibula (30%/46%) than boys with DMD (p < 0.05). They also had significantly larger diaphyseal tibiae/fibulae (74%/36%) and radii/ulnae (49%/31%) with thicker corticies and consequently greater bone strength. In contrast, boys with DMD had greater cortical density (4%). Over time, there were small significant differences in the rate of change of both muscle and bone parameters between healthy boys and boys with DMD. For both ambulant and non-ambulant boys with DMD the greatest changes in cortical bone were evident at the tibia. After two years boys with DMD had on average, 63% less bone strength than healthy boys. However, the most strikingly significant difference was in trabecular bone density for boys who became non-ambulant. By 2 years non-ambulant DMD boys had 53% less trabecular bone density at distal tibia than their healthy age matched peers compared with boys who remained ambulant who had 27% less trabecular bone density. In conclusion, bone and muscle strength is reduced for all boys with DMD even while they remain ambulant. However, tibia trabecular bone density loss is significantly accelerated in DMD boys who lose independent ambulation compared to DMD boys who remain ambulant despite equivalent levels of corticosteroid exposure