Traumatic rhabdomyolysis: rare but morbid, potentially lethal, and inconsistently monitored.

PURPOSE: Although traumatic rhabdomyolysis (TR) is shown to be associated with acute kidney injury (AKI), there are no large prospective epidemiological studies, interventional trials, official guidelines outlining the appropriate investigation, monitoring, and treatment on this poorly understood condition. We aimed to establish the contemporary epidemiology and describe current practices for TR to power future higher quality studies. We hypothesised that investigation and monitoring occur in an ad hoc fashion. MATERIAL AND METHODS: We conducted a 1-year retrospective cohort study of all patients > 16 years of age, with an ISS > 12 and, admitted to a level 1 trauma centre. Demographics, initial vital signs, admission laboratory values, and daily creatinine kinase (CK) values were collected. The primary outcome was TR (defined by CK > 5000 IU), secondary outcomes included AKI (KDIGO criteria), mortality, multiple organ failure, length of stay, and need for renal replacement therapy (RRT). RESULTS: 586 patients met inclusion criteria and 15 patients (2.56%) developed TR. CK testing occurred in 78 (13.1%) patients with 29 (37.7%) of these having values followed until downtrending. AKI occurred in 63 (10.8%) patients within the entire study population. Among those with TR, nine (60%) patients developed AKI. Patients with TR had higher ISS (median 29 vs 18) and mortality (26.7% vs 8.9%). DISCUSSION: Whilst TR appears rare without liberal screening, it is strongly associated with AKI. Given the poor outcomes, standardised monitoring, and liberal testing of CK could be justified in trauma patients with higher injury severity. This epidemiological data can help to define study populations and power future multicentre prospective studies on this infrequent yet morbid condition.

How to do laparoscopic repair of perforated anterior duodenal ulcers: a 'three arches' falciform patch technique simplifies the approach.

Laparoscopic repair of perforated duodenal ulcers has proven superior results to open procedures though uptake has been poor. We describe the 'three arches' technique as a means of reducing technical difficulty and improving operative efficiency. Our case series of patients undergoing this technique for perforated peptic ulcer disease demonstrates comparable results to other methods of repair.

A Hybrid Architecture (CO-CONNECT) to Facilitate Rapid Discovery and Access to Data Across the United Kingdom in Response to the COVID-19 Pandemic: Development Study.

BACKGROUND: COVID-19 data have been generated across the United Kingdom as a by-product of clinical care and public health provision, as well as numerous bespoke and repurposed research endeavors. Analysis of these data has underpinned the United Kingdom's response to the pandemic, and informed public health policies and clinical guidelines. However, these data are held by different organizations, and this fragmented landscape has presented challenges for public health agencies and researchers as they struggle to find relevant data to access and interrogate the data they need to inform the pandemic response at pace. OBJECTIVE: We aimed to transform UK COVID-19 diagnostic data sets to be findable, accessible, interoperable, and reusable (FAIR). METHODS: A federated infrastructure model (COVID - Curated and Open Analysis and Research Platform [CO-CONNECT]) was rapidly built to enable the automated and reproducible mapping of health data partners' pseudonymized data to the Observational Medical Outcomes Partnership Common Data Model without the need for any data to leave the data controllers' secure environments, and to support federated cohort discovery queries and meta-analysis. RESULTS: A total of 56 data sets from 19 organizations are being connected to the federated network. The data include research cohorts and COVID-19 data collected through routine health care provision linked to longitudinal health care records and demographics. The infrastructure is live, supporting aggregate-level querying of data across the United Kingdom. CONCLUSIONS: CO-CONNECT was developed by a multidisciplinary team. It enables rapid COVID-19 data discovery and instantaneous meta-analysis across data sources, and it is researching streamlined data extraction for use in a Trusted Research Environment for research and public health analysis. CO-CONNECT has the potential to make UK health data more interconnected and better able to answer national-level research questions while maintaining patient confidentiality and local governance procedures.

Life-threatening gastrointestinal haemorrhage requiring surgical resection caused by SARS-CoV-2 induced ANCA associated vasculitis: A case report.

Introduction and importance: SARS-CoV-2 infection has been linked to the de novo diagnosis of various autoimmune conditions as well as flares in pre-existing disease. With such high prevalence of SARS-CoV-2 in the community, it is important to consider rare manifestations of autoimmune conditions when patients present with severe symptoms. Multi-specialty care is required to ensure optimal outcomes and prompt diagnosis. Case presentation: A 28-year-old male presented to our tertiary referral centre with progressive debilitating polyarthritis, a purpuric rash on both flanks and aphthous ulcers 6 weeks after infection with SARS-CoV-2. On the second day of admission, he developed severe gastrointestinal haemorrhage requiring multiple blood transfusions. Attempted angioembolisation failed to identify a site of active haemorrhage. On failing trial of conservative management, the decision was made to perform an exploratory laparotomy. The small bowel was found to have an extensive vasculitis requiring resection to control haemorrhage. Autoimmune serology revealed c-ANCA positivity with anti-PR3 antibodies. Clinical discussion: Patients presenting with acute vasculitic pathologies related to SARS-CoV-2 have the potential to rapidly progress to severe life-threatening gastrointestinal haemorrhage. Prompt surgical management is appropriate in selected cases. Conclusion: In the current era of COVID-19, the differential diagnosis of SARS-CoV-2 induced ANCA vasculitis must be considered for such cases with gastrointestinal haemorrhage. Compilation of similar cases and further studies are required to determine an optimal management pathway for these patients.

Acute kidney injury development in polytrauma and the safety of early repeated contrast studies: A retrospective cohort study.

BACKGROUND: The role of repeat intravenous contrast doses beyond initial contrast imaging in the development of acute kidney injury (AKI) for multiple injury patients admitted to the intensive care unit (ICU) is not fully understood. We hypothesized that additional contrast doses are potentially modifiable risk factors for worse outcomes. METHODS: An 8-year retrospective study of our institutional prospective postinjury multiple organ failure database was performed. Adult ICU admissions that survived >72 hours with Injury Severity Score (ISS) of >15 were included. Patients were grouped based on number of repeat contrast studies received after initial imaging. Initial vital signs, resuscitation data, and laboratory parameters were collected. Primary outcome was AKI (Kidney Disease: Improving Global Outcomes criteria), and secondary outcomes included contrast-induced acute kidney injury (CI-AKI; >25% or >44 µmol/L increase in creatinine within 72 hours of contrast administration), multiple organ failure, length of stay, and mortality. RESULTS: Six-hundred sixty-three multiple injury patients (age, 45.3 years [SD, 9.1 years]; males, 75%; ISS, 25 (interquartile range, 20-34); mortality, 5.4%) met the inclusion criteria. The incidence of AKI was 13.4%, and CI-AKI was 14.5%. Multivariate analysis revealed that receiving additional contrast doses within the first 72 hours was not associated with AKI (odds ratio, 1.33; confidence interval, 0.80-2.21; p = 0.273). Risk factors for AKI included higher ISS ( p < 0.0007), older age ( p = 0.0109), higher heart rate ( p = 0.0327), lower systolic blood pressure ( p = 0.0007), and deranged baseline blood results including base deficit ( p = 0.0042), creatinine ( p < 0.0001), lactate ( p < 0.0001), and hemoglobin ( p = 0.0085). Acute kidney injury was associated with worse outcomes (ICU length of stay: 8 vs. 3 days, p < 0.0001; mortality: 16% vs. 3.8%, p < 0.0001; MOF: 42% vs. 6.6%, p < 0.0001). CONCLUSION: There is a limited role of repeat contrast administration in AKI development in ICU-admitted multiple injury patients. The clinical significance of CI-AKI is likely overestimated, and it should not compromise essential secondary imaging from the ICU. Further prospective studies are needed to verify our results. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Portal vein stenting in the management of duodenal varices due to malignant obstruction: A case report and literature review.

INTRODUCTION AND IMPORTANCE: Ectopic varices of the small bowel are a rare complication of portal hypertension. There are various aetiologies that can cause portal vein hypertension such as portal vein obstruction. Each of these pathologies has their own management strategies. Currently, there is a paucity of literature demonstrating the best management for patients with malignant portal vein obstruction leading to these varices. CASE PRESENTATION: This report presents a case of a 66-year-old female who presented with recurrent per-rectal bleeding. Computed tomography angiography diagnosed duodenal varices in the context of malignant obstruction of the portal vein. Due to being a poor operative candidate, she underwent trans-hepatic portal vein stenting leading to resolution of her symptoms. CLINICAL DISCUSSION: To date, the management of portal vein obstruction due to various aetiologies has only been reported in case reports with no significant large-scale studies providing recommendations on the most appropriate treatment. This case demonstrates the role of palliative stenting for patients with portal hypertension due to malignant portal vein obstruction. CONCLUSION: Duodenal varices are a rare complication of portal vein obstruction. This article contributes to the literature by demonstrating that patients with complications associated with portal vein obstruction can benefit from stenting. For those with malignant obstruction, palliative stenting serves as an important therapeutic option.

Estimating antimicrobial usage based on sales to beef and dairy farms from UK veterinary practices.

BACKGROUND: Accurate estimation of antimicrobial use (AMU) is important in assessing reduction of agricultural AMU. This cross-sectional study aimed to evaluate several approaches for estimating AMU at the herd level and to report on AMU for beef and dairy farms in Scotland. METHODS: Pharmaceutical sales data for 75 cattle herds (2011-2015) were screened for antimicrobial products and aggregated by herd and year. Several denominators for usage estimates were calculated and compared for their suitability at the herd level. RESULTS: The median total mass of active ingredient sold per kg of bovine livestock was 9.5 mg/kg for beef herds and 14.3 mg/kg for dairy herds. The 'highest priority critically important' antimicrobials (HPCIA) were by total mass of active ingredient, 10.6% of all sales; by total defined daily dose veterinary (DDDVet), 29.8% and by DCDvet, 20.0%. These are the first estimates of AMU for beef cattle in the UK, and for cattle of any kind in Scotland. Estimates of herd-level usage based on population correction unit (PCU) were sensitive to low values for PCU for specific herd-years due to their demographic composition. CONCLUSION: Pharmaceutical sales data can provide useful estimates of AMU, but estimating usage per PCU is not appropriate for comparing groups of cattle with different demographic compositions or for setting herd-level targets. Total mass of active ingredient per kilogram of livestock is more stable and hence suitable than PCU-based methods for assessing AMU at the herd level.

Primary cervical screening with high risk human papillomavirus testing: observational study.

OBJECTIVE: To provide the first report on the main outcomes from the prevalence and incidence rounds of a large pilot of routine primary high risk human papillomavirus (hrHPV) testing in England, compared with contemporaneous primary liquid based cytology screening. DESIGN: Observational study. SETTING: The English Cervical Screening Programme. PARTICIPANTS: 578 547 women undergoing cervical screening in primary care between May 2013 and December 2014, with follow-up until May 2017; 183 970 (32%) were screened with hrHPV testing. INTERVENTIONS: Routine cervical screening with hrHPV testing with liquid based cytology triage and two early recalls for women who were hrHPV positive and cytology negative, following the national screening age and interval recommendations. MAIN OUTCOME MEASURES: Frequency of referral for a colposcopy; adherence to early recall; and relative detection of cervical intraepithelial neoplasia grade 2 or worse from hrHPV testing compared with liquid based cytology in two consecutive screening rounds. RESULTS: Baseline hrHPV testing and early recall required approximately 80% more colposcopies, (adjusted odds ratio 1.77, 95% confidence interval 1.73 to 1.82), but detected substantially more cervical intraepithelial neoplasia than liquid based cytology (1.49 for cervical intraepithelial neoplasia grade 2 or worse, 1.43 to 1.55; 1.44 for cervical intraepithelial neoplasia grade 3 or worse, 1.36 to 1.51) and for cervical cancer (1.27, 0.99 to 1.63). Attendance at early recall and colposcopy referral were 80% and 95%, respectively. At the incidence screen, the 33 506 women screened with hrHPV testing had substantially less cervical intraepithelial neoplasia grade 3 or worse than the 77 017 women screened with liquid based cytology (0.14, 0.09 to 0.23). CONCLUSIONS: In England, routine primary hrHPV screening increased the detection of cervical intraepithelial neoplasia grade 3 or worse and cervical cancer by approximately 40% and 30%, respectively, compared with liquid based cytology. The very low incidence of cervical intraepithelial neoplasia grade 3 or worse after three years supports extending the screening interval.

Analysis of decreases in systemic arterial pressure and heart rate in response to the hydrogen sulfide donor sodium sulfide.

The actions of hydrogen sulfide (H2S) on the heart and vasculature have been extensively reported. However, the mechanisms underlying the effects of H2S are unclear in the anesthetized rat. The objective of the present study was to investigate the effect of H2S on the electrocardiogram and examine the relationship between H2S-induced changes in heart rate (HR), mean arterial pressure (MAP), and respiratory function. Intravenous administration of the H2S donor Na2S in the anesthetized Sprague-Dawley rat decreased MAP and HR and produced changes in respiratory function. The administration of Na2S significantly increased the RR interval at some doses but had no effect on PR or corrected QT(n)-B intervals. In experiments where respiration was maintained with a mechanical ventilator, we observed that Na2S-induced decreases in MAP and HR were independent of respiration. In experiments where respiration was maintained by mechanical ventilation and HR was maintained by cardiac pacing, Na2S-induced changes in MAP were not significantly altered, whereas changes in HR were abolished. Coadministration of glybenclamide significantly increased MAP and HR responses at some doses, but methylene blue, diltiazem, and ivabradine had no significant effect compared with control. The decreases in MAP and HR in response to Na2S could be dissociated and were independent of changes in respiratory function, ATP-sensitive K+ channels, methylene blue-sensitive mechanism involving L-type voltage-sensitive Ca2+ channels, or hyperpolarization-activated cyclic nucleotide-gated channels. Cardiovascular responses observed in spontaneously hypertensive rats were more robust than those in Sprague-Dawley rats.NEW & NOTEWORTHY H2S is a gasotransmitter capable of producing a decrease in mean arterial pressure and heart rate. The hypotensive and bradycardic effects of H2S can be dissociated, as shown with cardiac pacing experiments. Responses were not blocked by diltiazem, ivabradine, methylene blue, or glybenclamide.

Rationale for nebivolol/valsartan combination for hypertension: review of preclinical and clinical data.

: To treat hypertension, combining two or more antihypertensive drugs from different classes is often necessary. ß-Blockers and renin-angiotensin-aldosterone system inhibitors, when combined, have been deemed 'less effective' based on partially overlapping mechanisms of action and limited evidence. Recently, the single-pill combination (SPC) of nebivolol (Neb) 5 mg - a vasodilatory ß1-selective antagonist/ß3 agonist - and valsartan 80 mg, an angiotensin II receptor blocker, was US Food and Drug Administration-approved for hypertension. Pharmacological profiles of Neb and valsartan, alone and combined, are well characterized. In addition, a large 8-week randomized trial in stages I-II hypertensive patients (N = 4161) demonstrated greater blood pressure-reducing efficacy for Neb/valsartan SPCs than component monotherapies with comparable tolerability. In a biomarkers substudy (N = 805), Neb/valsartan SPCs prevented valsartan-induced increases in plasma renin, and a greater reduction in plasma aldosterone was observed with the highest SPC dose vs. valsartan 320 mg/day. This review summarizes preclinical and clinical evidence supporting Neb/valsartan as an efficacious and well tolerated combination treatment for hypertension.

Efficacy of nebivolol-valsartan single-pill combination in obese and nonobese patients with hypertension.

Antihypertensive efficacy of single-pill combinations (SPCs) consisting of a ß1 -selective adrenergic blocker with vasodilatory properties via ß3 -agonism (nebivolol) and an angiotensin II receptor blocker (valsartan) was demonstrated in an 8-week phase 3 trial (NCT01508026). In this post hoc analysis, seated blood pressure, heart rate, 24-hour ambulatory blood pressure monitoring, plasma aldosterone, estimated glomerular filtration rate, and safety measures were assessed in obese (body mass index >32 kg/m2 ; n=1823) and nonobese (body mass index <27 kg/m2 ; n=847) adults with hypertension (stage I or II) treated with nebivolol-valsartan SPCs, nebivolol or valsartan monotherapy, or placebo. At week 8, reductions from baseline in blood pressure and ambulatory blood pressure monitoring were greater with SPCs and most nebivolol and valsartan monotherapy doses vs placebo regardless of obesity status. Aldosterone declined with all active treatments and estimated glomerular filtration rate remained steady. The nebivolol-valsartan 5/80 mg/d SPC was efficacious regardless of degree of obesity.

A mathematical algorithm for quantification of CT image noise.

Quantification of computed tomography (CT) noise helps in determination of radiation dosage requirements for adequate image quality. Clinical methods used include calculation of the standard deviation (SD) of a selected region of interest (ROI). In industry, wavelet decomposition has been used for image compression while removing high-frequency noise. We evaluated a cohort of 74 consecutive patients referred for coronary artery calcium scoring and quantitated noise within a 16×16 ROI in the ascending aorta using the traditional SD method and also using a two-dimensional dyadic wavelet decomposition method. Clinically, noise has been shown to be proportional to patient weight and also body mass index (BMI), which is a derived value from height and weight. Noise for both methods was plotted against patient parameters of height, weight, waist circumference and calculated BMI. A regression line was calculated and coefficient of determination (CoD) calculated for each. The CoD was better for height, weight, and waist circumference using the wavelet method as compared to the traditional SD method. The wavelet method of quantification of image noise may be an improved method as compared to the SD method. This method could help further refine an imaging system's determination of radiation dosage requirements to obtain a satisfactory quality image.

Methodological evaluation of the noninvasive estimation of central systolic blood pressure in nontreated patients: the Bogalusa Heart Study.

OBJECTIVES: This study sought to compare the estimation of central systolic blood pressure (cSBP) obtained by two different noninvasive devices, in addition to its comparisons with measured peripheral systolic blood pressure (pSBP), in a biracial (Black/White) community-based cohort. PARTICIPANTS AND METHODS: Estimations of cSBP by applanation tonometry were obtained in 586 participants of the Bogalusa Heart Study (mean age: 43.5 years; 69% White, 54% women) using two different commonly used instruments: Omron HEM-9000AI and SphygmoCor CPV. pSBP was measured using a standard auscultatory technique. RESULTS: The estimation of cSBP by the Omron device was higher than that of the SphygmoCor device (124.2±17.1 vs. 111.4±15.2 mmHg, P<0.001). Moreover, cSBP by Omron was significantly higher than peripheral blood pressure (124.2±17.1 vs. 119.4±15.6 mmHg, P<0.001), whereas cSBP by SphygmoCor was significantly lower than pSBP (111.4±15.2 vs. 119.4±15.6 mmHg, P<0.001). Similar results were observed in race-specific and sex-specific analyses. CONCLUSION: These findings support the hypothesis that notable differences exist in the estimation of cSBP provided by the instruments utilized in this study. Further standardization studies are required to establish the most appropriate noninvasive estimation of cSBP before this parameter may be considered in the assessment, prediction, and prevention of cardio-metabolic risk and overt cardiovascular disease in clinical practice.

Nebivolol has a beneficial effect in monocrotaline-induced pulmonary hypertension.

Pulmonary hypertension is a rare disorder that, without treatment, is progressive and fatal within 3-4 years. Current treatment involves a diverse group of drugs that target the pulmonary vascular bed. In addition, strategies that increase nitric oxide (NO) formation have a beneficial effect in rodents and patients. Nebivolol, a selective ß1 adrenergic receptor-blocking agent reported to increase NO production and stimulate ß3 receptors, has vasodilator properties suggesting that it may be beneficial in the treatment of pulmonary hypertension. The present study was undertaken to determine whether nebivolol has a beneficial effect in monocrotaline-induced (60 mg/kg) pulmonary hypertension in the rat. These results show that nebivolol treatment (10 mg/kg, once or twice daily) attenuates pulmonary hypertension, reduces right ventricular hypertrophy, and improves pulmonary artery remodeling in monocrotaline-induced pulmonary hypertension. This study demonstrates the presence of ß3 adrenergic receptor immunoreactivity in pulmonary arteries and airways and that nebivolol has pulmonary vasodilator activity. Studies with ß3 receptor agonists (mirabegron, BRL 37344) and antagonists suggest that ß3 receptor-mediated decreases in systemic arterial pressure occur independent of NO release. Our results suggest that nebivolol, a selective vasodilating ß1 receptor antagonist that stimulates ß3 adrenergic receptors and induces vasodilation by increasing NO production, may be beneficial in treating pulmonary hypertensive disorders.

Fixed-dose combination therapy of nebivolol and valsartan for the treatment of hypertension.

Recent large clinical trials have refuted earlier suggestions from the Joint National Committee 8 committee that less aggressive targets for blood pressure control were all that could be justified in most hypertensive patients. It now does appear that in fact "lower is better," with blood pressure targets < 120/80 mm Hg appropriate for many hypertensive patients. Two drug combinations are often indicated as initial therapy if a 20/10 mm Hg or greater blood pressure reduction is necessary to reach target. Combinations consisting of ß-blockers and renin-angiotensin-aldosterone system inhibitors have previously been deemed "less effective," based on partially overlapping mechanisms of action and limited clinical trial evidence. Nebivolol is a vasodilating ß1-selective blocker and ß3- adrenoceptor agonist; ß3-adrenoceptor activation increases nitric oxide concentrations and thus explains the vasodilatory effect. A recent 8-week randomized trial (N=4,161) in individuals with stage 1-2 hypertension demonstrated that single-pill fixed dose combinations (FDC) of nebivolol and valsartan, an angiotensin II subtype 1 receptor blocker, were more effective in reducing blood pressure than the corresponding monotherapies, with comparable tolerability. In addition, an ABPM-biomarkers substudy from that trial (n=805) demonstrated that the FDC prevented a valsartan-induced increase in plasma renin activity, and that the nebivolol/valsartan 20/320 mg/day dose reduced plasma aldosterone concentration significantly more than valsartan 320 mg/day. This article will describe the properties of nebivolol that make it unique and separate it from other ß-blockers, and will further support the pharmacological advantages of this particular combination.

Prehypertension: Defining the Transitional Phenotype.

More than a simple "transitional stage" defined by covenanted cut points of systolic pressure from 120 to 139 mm of mercury (mm Hg) or a diastolic pressure from 80 to 89 mm Hg, prehypertension should be referred to as a categorical term that defines a specific phenotype in the progression from the "absence of disease" to clinically overt disease. While the currently utilized definition of prehypertension stresses the use of blood pressure cut points to establish the diagnosis, it is of relevance to direct our attention to the structural and functional hemodynamic alterations that occur in response to the two cardinal abnormalities in the development of prehypertension and hypertension: autonomic dysfunction and arterial remodeling. Our current review addresses these aspects of the pathophysiology or prehypertension on its progression to hypertension and suggests a new approach to its classification.

Correlations of plasma renin activity and aldosterone concentration with ambulatory blood pressure responses to nebivolol and valsartan, alone and in combination, in hypertension.

After demonstration of the antihypertensive efficacy of the combination of the beta-blocker nebivolol and the angiotensin receptor blocker valsartan in an 8-week, randomized, placebo-controlled trial (N = 4161), we now report the effects of this treatment on the renin-angiotensin-aldosterone system in a substudy (n = 805). Plasma renin activity increased with valsartan (54%-73%) and decreased with nebivolol (51%-65%) and the combination treatment (17%-39%). Plasma aldosterone decreased with individual treatments (valsartan, 11%-22%; nebivolol, 20%-26%), with the largest reduction (35%) observed with maximum combination dose (20 mg nebivolol/320 mg valsartan). Baseline ln(plasma renin activity) correlated with the 8-week reductions in 24-hour systolic and diastolic BP following treatments with the combination (all doses combined, P = .003 and P < .001) and nebivolol (both, P < .001), but not with valsartan. Baseline ln(aldosterone) correlated with 24-hour systolic and diastolic BP reductions following combination treatment only (P < .001 and P = .005). The implications of the renin-angiotensin-aldosterone system effects of this beta blocker-angiotensin receptor blocker combination should be explored further.