Outcomes for Children With Vascular Ring Repair Using a Simple Surgical Approach.

INTRODUCTION: Vascular Rings (VRs) are congenital malformations of the aortic arch that can compress the trachea and esophagus producing symptoms. Approximately, 5%-10% of patients experience persistent symptoms postrepair and 9% require reintervention. There are various approaches to repair-simple ligation and division of the ring or more complex procedures. Our objective was to describe outcomes for VR repair using a "simple" surgical approach. METHODS: We identified patients who underwent VR repair from 2012 to 2022 at our institution. Clinical and surgical data, demographics, intraoperative, and postoperative outcomes were extracted from their electronic medical records. Outcomes were analyzed and regression analysis was used to identify risk factors for residual symptoms after repair. RESULTS: Ninety three patients with VR repair were included. Prevalence of symptoms were reduced following surgery (80% preoperative versus 13% postoperative, P 0.03). Tracheomalacia also decreased from 16% to 7% postrepair. No deaths were reported in our cohort and 2% of our patients required reintervention. Multivariable regression analysis showed that preoperative tracheomalacia was associated with having persistent symptoms after VR repair (odds ratio 6.2, 95% CI 1.02-37.6). CONCLUSIONS: Our institutional experience using a simple surgical approach showed a significant decrease in symptoms, a very low reintervention rate and no mortality. Preoperative tracheomalacia can be a risk factor for persistent symptoms postrepair. We believe a simple surgical approach for children with complete VR repair can be effective in relieving symptoms.

Right ventricular dysfunction in patients with COVID-19 pneumonitis whose lungs are mechanically ventilated: a multicentre prospective cohort study.

Cardiovascular complications due to COVID-19, such as right ventricular dysfunction, are common. The combination of acute respiratory distress syndrome, invasive mechanical ventilation, thromboembolic disease and direct myocardial injury creates conditions where right ventricular dysfunction is likely to occur. We undertook a prospective, multicentre cohort study in 10 Scottish intensive care units of patients with COVID-19 pneumonitis whose lungs were mechanically ventilated. Right ventricular dysfunction was defined as the presence of severe right ventricular dilation and interventricular septal flattening. To explore the role of myocardial injury, high-sensitivity troponin and N-terminal pro B-type natriuretic peptide plasma levels were measured in all patients. We recruited 121 patients and 118 (98%) underwent imaging. It was possible to determine the primary outcome in 112 (91%). Severe right ventricular dilation was present in 31 (28%), with interventricular septal flattening present in nine (8%). Right ventricular dysfunction (the combination of these two parameters) was present in seven (6%, 95%CI 3-13%). Thirty-day mortality was 86% in those with right ventricular dysfunction as compared with 45% in those without (p = 0.051). Patients with right ventricular dysfunction were more likely to have: pulmonary thromboembolism (p < 0.001); higher plateau airway pressure (p = 0.048); lower dynamic compliance (p = 0.031); higher plasma N-terminal pro B-type natriuretic peptide levels (p = 0.006); and raised plasma troponin levels (p = 0.048). Our results demonstrate a prevalence of right ventricular dysfunction of 6%, which was associated with increased mortality (86%). Associations were also observed between right ventricular dysfunction and aetiological domains of: acute respiratory distress syndrome; ventilation; thromboembolic disease; and direct myocardial injury, implying a complex multifactorial pathophysiology.

Is there a relationship between the presence of the binary toxin genes in Clostridium difficile strains and the severity of C. difficile infection (CDI)?

Some strains of Clostridium difficile produce a binary toxin, in addition to the main C. difficile virulence factors (toxins A and B). There have been conflicting reports regarding the role of binary toxin and its relationship to the severity of C. difficile infection (CDI). Samples, isolates and clinical data were collected as part of a prospective multicentre diagnostic study. Clostridium difficile isolates (n = 1259) were tested by polymerase chain reaction (PCR) assay to detect binary toxin genes cdtA and cdtB. The PCR binary toxin gene results were compared with clinical severity and outcome data, including 30-day all-cause mortality. The 1259 isolates corresponded to 1083 different patients (October 2010 to September 2011). The prevalence of binary toxin positive strains was significantly higher in faecal samples with detectable toxin A/B than in those without toxin but that were positive by cytotoxigenic culture (26.3% vs. 10.3%, p < 0.001). The presence of binary toxin correlated moderately with markers of CDI severity (white cell count, serum albumin concentration and serum creatinine concentration). However, the risk ratio for all-cause mortality was 1.68 for binary toxin positive patients and patients were significantly less likely to survive if they had CDI caused by a binary toxin gene positive strain, even after adjusting for age (p < 0.001). The presence of binary toxin genes does not predict the clinical severity of CDI, but it is significantly associated with the risk of all-cause mortality.

Biochars Reduce Mine Land Soil Bioavailable Metals.

Biochar has been proposed as an amendment to remediate mine land soils; however, it could be advantageous and novel if feedstocks local to mine land sites were used for biochar production. Two different feedstocks (pine beetle-killed lodgepole pine [] and tamarisk [ spp.]), within close proximity to mine land-affected soils, were used to create biochars to determine if they have the potential to reduce metal bioavailability. Four different mine land soils, contaminated with various amounts of Cd, Cu, Pb, and Zn, received increasing amounts of biochar (0, 5, 10, and 15% by wt). Soil pH and metal bioavailability were determined, and the European Community Bureau of Reference (BCR) sequential extraction procedure was used to identify pools responsible for potential shifts in bioavailability. Increasing biochar application rates caused increases in soil pH (initial, 3.97; final, 7.49) and 55 to 100% (i.e., no longer detectable) decreases in metal bioavailability. The BCR procedure supported the association of Cd with carbonates, Cu and Zn with oxyhydroxides and carbonates, and Pb with oxyhydroxides; these phases were likely responsible for the reduction in heavy metal bioavailability. This study proved that both of these feedstocks local to abandoned mining operations could be used to create biochars and reduce heavy metal bioavailability in mine land soils.

Usefulness of High-Quality Core Genome Single-Nucleotide Variant Analysis for Subtyping the Highly Clonal and the Most Prevalent Salmonella enterica Serovar Heidelberg Clone in the Context of Outbreak Investigations.

Salmonella enterica serovar Heidelberg is the second most frequently occurring serovar in Quebec and the third-most prevalent in Canada. Given that conventional pulsed-field gel electrophoresis (PFGE) subtyping for common Salmonella serovars, such as S. Heidelberg, yields identical subtypes for the majority of isolates recovered, public health laboratories are desperate for new subtyping tools to resolve highly clonal S. Heidelberg strains involved in outbreak events. As PFGE was unable to discriminate isolates from three epidemiologically distinct outbreaks in Quebec, this study was conducted to evaluate whole-genome sequencing (WGS) and phylogenetic analysis as an alternative to conventional subtyping tools. Genomes of 46 isolates from 3 Quebec outbreaks (2012, 2013, and 2014) supported by strong epidemiological evidence were sequenced and analyzed using a high-quality core genome single-nucleotide variant (hqSNV) bioinformatics approach (SNV phylogenomics [SNVphyl] pipeline). Outbreaks were indistinguishable by conventional PFGE subtyping, exhibiting the same PFGE pattern (SHEXAI.0001/SHEBNI.0001). Phylogenetic analysis based on hqSNVs extracted from WGS separated the outbreak isolates into three distinct groups, 100% concordant with the epidemiological data. The minimum and maximum number of hqSNVs between isolates from the same outbreak was 0 and 4, respectively, while >59 hqSNVs were measured between 2 previously indistinguishable outbreaks having the same PFGE and phage type, thus corroborating their distinction as separate unrelated outbreaks. This study demonstrates that despite the previously reported high clonality of this serovar, the WGS-based hqSNV approach is a superior typing method, capable of resolving events that were previously indistinguishable using classic subtyping tools.

Comparison of the Vidas C. difficile GDH Automated Enzyme-Linked Fluorescence Immunoassay (ELFA) with Another Commercial Enzyme Immunoassay (EIA) (Quik Chek-60), Two Selective Media, and a PCR Assay for gluD for Detection of Clostridium difficile in Fecal Samples.

Prevention and management of Clostridium difficile infection (CDI) can be improved by rapid and reliable diagnostics. The Vidas C. difficile glutamate dehydrogenase assay had performance comparable to that of the Quik Chek-60 assay (overall agreement, 95%) and a sensitivity of >93%; thus, it is suitable as the first test in two-stage algorithms for a CDI diagnosis.

Variation among Bm86 sequences in Rhipicephalus (Boophilus) microplus ticks collected from cattle across Thailand.

Anti-tick vaccines based on recombinant homologues Bm86 and Bm95 have become a more cost-effective and sustainable alternative to chemical pesticides commonly used to control the cattle tick, Rhipicephalus (Boophilus) microplus. However, Bm86 polymorphism among geographically separate ticks is reportedly associated with reduced effectiveness of these vaccines. The purpose of this study was to investigate the variation of Bm86 among cattle ticks collected from Northern, Northeastern, Central and Southern areas across Thailand. Bm86 cDNA and deduced amino acid sequences representing 29 female tick midgut samples were 95.6-97.0 and 91.5-93.5 % identical to the nucleotide and amino acid reference sequences, respectively, of the Australian Yeerongpilly vaccine strain. Multiple sequence analyses of these Bm86 variants indicated geographical relationships and polymorphism among Thai cattle ticks. Two larger groups of cattle tick strains were discernable based on this phylogenetic analysis of Bm86, a Thai group and a Latin American group. Thai female and male cattle ticks (50 pairs) were also subjected to detailed morphological characterization to confirm their identity. The majority of female ticks had morphological features consistent with those described for R. (B.) microplus, whereas, curiously, the majority of male ticks were more consistent with the recently re-instated R. (B.) australis. A number of these ticks had features consistent with both species. Further investigations are warranted to test the efficacies of rBm86-based vaccines to homologous and heterologous challenge infestations with Thai tick strains and for in-depth study of the phylogeny of Thai cattle ticks.

Natural variation in light sensitivity of Arabidopsis.

Because plants depend on light for growth, their development and physiology must suit the particular light environment. Plants native to different environments show heritable, apparently adaptive, changes in their response to light. As a first step in unraveling the genetic and molecular basis of these naturally occurring differences, we have characterized intraspecific variation in a light-dependent developmental process-seedling emergence. We examined 141 Arabidopsis thaliana accessions for their response to four light conditions, two hormone conditions and darkness. There was significant variation in all conditions, confirming that Arabidopsis is a rich source of natural genetic diversity. Hierarchical clustering revealed that some accessions had response patterns similar to known photoreceptor mutants, suggesting changes in specific signaling pathways. We found that the unusual far-red response of the Lm-2 accession is due to a single amino-acid change in the phytochrome A (PHYA) protein. This change stabilizes the light-labile PHYA protein in light and causes a 100-fold shift in the threshold for far-red light sensitivity. Purified recombinant Lm-2 PHYA also shows subtle photochemical differences and has a reduced capacity for autophosphorylation. These biochemical changes contrast with previously characterized natural alleles in loci controlling plant development, which result in altered gene expression or loss of gene function.

An evaluation of the effects of a service change from epidurals to rectus sheath catheters on postoperative pain.

Epidurals are frequently used as part of multi-modal perioperative analgesia. They are widely accepted as providing excellent pain relief but are associated with side-effects, have a significant failure rate and can limit a patient's mobility. We report on our use of rectus sheath catheters (RSCs), in conjunction with intravenous opiate via patient controlled analgesia (PCA), as a means of providing analgesia post-laparotomy for gynaecological oncological patients. Our experience is that this offers an alternative method of providing equivalent analgesia, avoiding the risks associated with epidural use and possibly has a role in reducing length of patient stay, although this requires further investigation.

Microvascular arterial disease of the brain and the heart: a shared pathogenesis.

Microvascular arterial disease in the heart manifest as coronary microvascular dysfunction. This condition causes microvascular angina and is associated increased morbidity and mortality. Microvascular arterial disease in the brain is referred to as cerebrovascular small vessel disease. This is responsible for 45% of dementias and 25% of ischaemic strokes. The heart and brain share similar vascular anatomy and common pathogenic risk factors are associated with the development of both coronary microvascular dysfunction and cerebrovascular small vessel disease. Microvascular disease in the heart and brain also appear to share common multisystem pathophysiological mechanisms. Further studies on diagnostic approaches, epidemiology and development of disease-modifying therapy seem warranted.

Hybrid Norwood for Hypoplastic Left Heart Syndrome With Rare Aortic Arch Anatomy.

We describe the hybrid Norwood as first-stage palliation for a patient with hypoplastic left heart syndrome, right aortic arch, right descending aorta, bilateral ductus arteriosus, and left innominate artery arising from the left ductus.

Standards for clinical trials for treating TB.

BACKGROUND: The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.METHODS: A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.RESULTS: Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.CONCLUSION: These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.

Vein graft failure: current clinical practice and potential for gene therapeutics.

Autologous saphenous vein is commonly used as a conduit to bypass atherosclerotic lesions in coronary and femoral arteries. Despite the wide use of arterial conduits, which are less susceptible to complications and failure, as alternative conduits, the saphenous vein will continue to be used in coronary artery bypass grafting until acceptable alternative approaches are evaluated. Hence, preservation of vein graft patency is essential for the long-term success. Gene therapy is attractive in this setting as an ex-vivo technology to genetically manipulate the conduit before grafting. The use of safe and efficient vectors for delivery is a necessity as well as a strategy to improve patency in the long term. Here, we review the current clinical practice, the pathogenesis of bypass graft failure and adenovirus-mediated gene therapy strategies designed to improve late vein graft failure by modulation of smooth muscle cells in the vein wall.

Irish Defence Forces combat medical technician training: experience of a novel university medical school-based programme.

AIMS: This study explores the opinions and experiences of Irish Defences Forces' (IDF) graduates from University College Dublin's Diploma in Military Medicine Care (DMMC). It aims to identify which aspects of medical education are relevant for the development of military graduates in the role of Combat Medical Technician (CMT) in future. METHODS: A validated Clinical Learning Environment Score tool was adapted and incorporated into an online survey. This was sent electronically to 71 graduates. Responses were anonymous. RESULTS: 38 (54%) graduates responded. Student feedback was positive regarding teaching and clinical placements in the DMMC. In total 16 (42%) students reported use of their new skills in their daily work. Of the 9 (24%) deployed overseas, all used their new skills. Emergency and occupational health skills were used more frequently, while advanced skills were used rarely. CONCLUSION: An increased emphasis on frequently used skills should be considered. Links to healthcare services would be of benefit to graduates in skills maintenance. Key advanced skills, such as intravenous cannulation and advanced airway management are rarely used but mechanisms to maintain them will improve the relevance of the programme to the CMT role. A change in how the IDF acknowledges qualifications may support more graduates in advancing and maintaining their career in the military medical workforce.

Left ventricular dysfunction and intra-ventricular dyssynchrony in idiopathic pulmonary arterial hypertension.

BACKGROUND: Left ventricular (LV) filling pressures are normal in idiopathic pulmonary arterial hypertension (IPAH). However, direct and indirect interactions between the RV and LV can affect LV performance. We explored LV strain and LV intra-ventricular dyssynchrony in IPAH using feature tracking CMR (CMR-FT). METHODS: Seventy IPAH patients and 40 healthy volunteers were included. Patients underwent CMR and right heart catheterisation. The 4-chamber cine was used to calculate LV longitudinal strain (EllLV). LV circumferential (EccLV) and radial strain (ErrLV) were derived from a short axis cine. LV longitudinal, circumferential and radial intra-ventricular dyssynchrony indices were calculated. RESULTS: There were no differences between the IPAH and healthy volunteer group in LV ejection fraction (66.1% vs 64.2% p = 0.6672). EccLV (-29.1 vs -32.1 p = 0.0323) and EllLV (-16.6 vs -23.7 p < 0.0001) were lower in IPAH. In patients with more severe disease, there was greater impairment of ErrLV compared to mild disease (50.9 vs 87.5 P < 0.0001). LV synchrony was impaired in all directions in IPAH. ErrLV was associated with RV ejection fraction (r = 0.66), RV end-systolic volume index (r = -0.59), pulmonary vascular resistance (PVR)(r = 0.51) and stroke volume index (SVI)(r = 0.44). In a multivariate model with age, SVI and PVR, ErrLV (HR 0.970 p = 002) and radial dyssynchrony (HR 3.759 p < 0.0001) independently predicted survival. CONCLUSION: In IPAH, LV is dyssynchronous with impaired function. Measures of LV strain and intraventricular synchrony were associated with known markers of disease severity. These LV variables which are likely to be related to ventricular interaction, may add incremental value to known prognostic variables in IPAH.

Prevention and early treatment of the long-term physical effects of COVID-19 in adults: design of a randomised controlled trial of resistance exercise-CISCO-21.

BACKGROUND: Coronavirus disease-19 (COVID-19) infection causes persistent health problems such as breathlessness, chest pain and fatigue, and therapies for the prevention and early treatment of post-COVID-19 syndromes are needed. Accordingly, we are investigating the effect of a resistance exercise intervention on exercise capacity and health status following COVID-19 infection. METHODS: A two-arm randomised, controlled clinical trial including 220 adults with a diagnosis of COVID-19 in the preceding 6 months. Participants will be classified according to clinical presentation: Group A, not hospitalised due to COVID but persisting symptoms for at least 4 weeks leading to medical review; Group B, discharged after an admission for COVID and with persistent symptoms for at least 4 weeks; or Group C, convalescing in hospital after an admission for COVID. Participants will be randomised to usual care or usual care plus a personalised and pragmatic resistance exercise intervention for 12 weeks. The primary outcome is the incremental shuttle walks test (ISWT) 3 months after randomisation with secondary outcomes including spirometry, grip strength, short performance physical battery (SPPB), frailty status, contacts with healthcare professionals, hospitalisation and questionnaires assessing health-related quality of life, physical activity, fatigue and dyspnoea. DISCUSSION: Ethical approval has been granted by the National Health Service (NHS) West of Scotland Research Ethics Committee (REC) (reference: GN20CA537) and recruitment is ongoing. Trial findings will be disseminated through patient and public forums, scientific conferences and journals. TRIAL REGISTRATION: ClinicialTrials.gov NCT04900961 . Prospectively registered on 25 May 2021.

Stressed hearts in children with obesity and diabetes: a cause for concern?

Obesity in young people is an emerging public health problem, particularly because of its association with type 2 diabetes. Since obesity and diabetes contribute to the development of cardiovascular disease in adults, the question arises as to whether or not these conditions may be associated with cardiovascular abnormalities in children and adolescents. In this issue of Diabetologia, Shah et al. report the results of a cross-sectional study of heart structure and function in 612 adolescents and young adults (aged 10-24 years) subdivided into three groups: (1) those with obesity and type 2 diabetes; (2) those with type 2 diabetes but without obesity; and (3) lean healthy controls. Their results revealed that left ventricular mass (indexed to body surface area) was greater in the obese individuals than in lean controls. Left ventricular systolic function was more dynamic in obese participants and obese participants with type 2 diabetes compared with lean controls, whereas systolic function was comparable in obese patients with or without type 2 diabetes. Furthermore, compared with the healthy lean control participants, diastolic function was impaired in the obese group and further impaired in the obese individuals with diabetes. These results, and those of a few other similar studies, lend support to the notion that obesity and diabetes in children cause subtle abnormalities in cardiovascular structure and function. The present commentary discusses potential mechanisms and possible clinical ramifications for such findings.

B-type natriuretic peptide predicts long-term survival after major non-cardiac surgery.

BACKGROUND: The prediction of long-term survival after surgery is complex. Natriuretic peptides can predict short-term postoperative cardiac morbidity and mortality. This study aims to determine the long-term prognostic significance of preoperative B-type natriuretic peptide (BNP) concentration after major non-cardiac surgery. METHODS: We conducted a prospective single-centre observational cohort study in a West of Scotland teaching hospital. Three hundred and forty-five patients undergoing major non-cardiac surgery were included. The primary endpoint was long-term all-cause mortality. RESULTS: Overall survival was 67.8% (234/345), with 27 postoperative deaths (within 42 days) and 84 deaths at subsequent follow-up (median follow-up 953 days). A BNP concentration of >87.5 pg ml(-1) best predicted mortality, and the mean survival of patients with an elevated BNP (>87.5 pg ml(-1)) was 731.9 (95% CI 613.6-850.2) days compared with 1284.6 days [(95% CI 1219.3-1350.0), P<0.001] in patients with a BNP<87.5 pg ml(-1). BNP was an independent predictor of survival. CONCLUSIONS: BNP is an independent predictor of long-term survival after major non-cardiac surgery. A simple preoperative blood test can provide predictive information on future risk of death, and potentially has a role in preoperative risk assessment.

Ritonavir-induced acute kidney injury: kidney biopsy findings and review of literature.

Ritonavir therapy is not generally considered nephrotoxic. We report a case of acute kidney injury secondary to ritonavir, with kidney biopsy demonstrating extensive acute tubular injury. This is the first report of a kidney biopsy and pathology in acute kidney injury associated with ritonavir. A review of published medical literature on the topic is also presented.

Validation of the Hamilton Program for Schizophrenia Voices Questionnaire: Associations with emotional distress and wellbeing, and invariance across diagnosis and sex.

BACKGROUND: Voice-hearing is a transdiagnostic experience with evident negative effects on patients. Good quality measurement is needed to further elucidate the nature, impact and treatment of voice-hearing experiences across patient groups. The Hamilton Program for Schizophrenia Voices Questionnaire (HPSVQ) is a brief self-report measure which requires further psychometric evaluation. METHODS: Using data from a transdiagnostic sample of 401 adult UK patients, the fit of a conceptual HPSVQ measurement model, proposing a separation between physical and emotional voice-hearing characteristics, was tested. A structural model was examined to test associations between voice-hearing, general emotional distress (depression, anxiety, stress) and wellbeing. The invariance of model parameters was examined across diagnosis and sex. RESULTS: The final measurement model comprised two factors named 'voice severity' and 'voice-related distress'. The former comprised mainly physical voice characteristics and the latter mainly distress and other negative impacts. Structural model results supported voice-related distress as mediating the associations between voice severity and emotional distress and wellbeing. Model parameters were invariant across psychosis versus non-psychosis diagnosis and partially invariant across sex. Females experienced more severe and distressing voices and a more direct association between voice severity and general anxiety was evident. CONCLUSIONS: The HPSVQ is a useful self-report measure of voice-hearing with some scope for further exploration and refinement. Voice-related distress appears a key mechanism by which voice severity predicts general distress and wellbeing. Whilst our data broadly support interventions targeting voice-related distress for all patients, females may benefit especially from interventions targeting voice severity and strategies for responding.