Multi-center implementation of rapid whole genome sequencing provides additional evidence of its utility in the pediatric inpatient setting.

Objective: Multi-center implementation of rapid whole genome sequencing with assessment of the clinical utility of rapid whole genome sequencing (rWGS), including positive, negative and uncertain results, in admitted infants with a suspected genetic disease. Study design: rWGS tests were ordered at eight hospitals between November 2017 and April 2020. Investigators completed a survey of demographic data, Human Phenotype Ontology (HPO) terms, test results and impacts of results on clinical care. Results: A total of 188 patients, on general hospital floors and intensive care unit (ICU) settings, underwent rWGS testing. Racial and ethnic characteristics of the tested infants were broadly representative of births in the country at large. 35% of infants received a diagnostic result in a median of 6 days. The most common HPO terms for tested infants indicated an abnormality of the nervous system, followed by the cardiovascular system, the digestive system, the respiratory system and the head and neck. Providers indicated a major change in clinical management because of rWGS for 32% of infants tested overall and 70% of those with a diagnostic result. Also, 7% of infants with a negative rWGS result and 23% with a variant of unknown significance (VUS) had a major change in management due to testing. Conclusions: Our study demonstrates that the implementation of rWGS is feasible across diverse institutions, and provides additional evidence to support the clinical utility of rWGS in a demographically representative sample of admitted infants and includes assessment of the clinical impact of uncertain rWGS results in addition to both positive and negative results.

Year in Review 2022: Noteworthy Literature in Cardiac Anesthesiology.

Last year researchers made substantial progress in work relevant to the practice of cardiac anesthesiology. We reviewed 389 articles published in 2022 focused on topics related to clinical practice to identify 16 that will impact the current and future practice of cardiac anesthesiology. We identified 4 broad themes including risk prediction, postoperative outcomes, clinical practice, and technological advances. These articles are representative of the best work in our field in 2022.

The feasibility of using manual segmentation in a multifeature computer-aided diagnosis system for classification of skin lesions: a retrospective comparative study.

OBJECTIVES: To investigate the feasibility of manual segmentation by users of different backgrounds in a previously developed multifeature computer-aided diagnosis (CADx) system to classify melanocytic and non-melanocytic skin lesions based on conventional digital photographic images. METHODS: In total, 347 conventional photographs of melanocytic and non-melanocytic skin lesions were retrospectively reviewed, and manually segmented by two groups of physicians, dermatologists and general practitioners, as well as by an automated segmentation software program, JSEG. The performance of CADx based on inputs from these two groups of physicians and that of the JSEG program was compared using feature agreement analysis. RESULTS: The estimated area under the receiver operating characteristic curve for classification of benign or malignant skin lesions based were comparable on individual segmentation by the gold standard (0.893, 95% CI 0.856 to 0.930), dermatologists (0.886, 95% CI 0.863 to 0.908), general practitioners (0.883, 95% CI 0.864 to 0.903) and JSEG (0.856, 95% CI 0.812 to 0.899). The agreement in the malignancy probability scores among the physicians was excellent (intraclass correlation coefficient: 0.91). By selecting an optimal cut-off value of malignancy probability score, the sensitivity and specificity were 80.07% and 81.47% for dermatologists and 79.90% and 80.20% for general practitioners. CONCLUSIONS: This study suggests that manual segmentation by general practitioners is feasible in the described CADx system for classifying benign and malignant skin lesions.

Comparison of Surgisis, AlloDerm, and Vicryl Woven Mesh grafts for abdominal wall defect repair in an animal model.

BACKGROUND: Surgisis and AlloDerm, two biosynthetic materials, have been previously used with success in abdominal wall repairs in the setting of contaminated fields. Historically, Vicryl Woven Mesh, a synthetic material, has also been used in such settings as a temporary bridge for abdominal wall reconstruction. This study compares Surgisis and AlloDerm with Vicryl Woven Mesh with respect to tensile strength, collagen remodeling, and neovascularization using a rat hernia model. METHODS: A prospective randomized trial of 54 Sprague-Dawley rats were assigned to the Surgisis, AlloDerm, or Vicryl Woven Mesh group with baseline, 30-day, and 60-day end points. A 1.5-cm x 5.0-cm defect was created in the right abdominis rectus muscle and repaired with an underlay bridge graft using the different treatment materials. Tensile strength was measured using an Instron tensiometer. Histologic specimens were evaluated for neovascularization, collagen deposition, and collagen organization at the 30- and 60-day time points. RESULTS: Surgisis had significantly greater tensile strength compared to Vicryl Woven Mesh at the baseline time point (0.142 vs. 0.091 MPa, p < 0.05). There were no differences between groups tensile strength at 30 or 60 days postoperatively. The Vicryl Woven Mesh and AlloDerm groups showed increases in tensile strength at 30 days postoperatively versus baseline (p < 0.05). Vicryl Woven Mesh, Surgisis, and AlloDerm all showed increases in tensile strength at 60 days postoperatively compared to 30 days postoperatively and at baseline (p < 0.05). Surgisis and AlloDerm had significantly greater (p < 0.05) amounts of collagen deposition and organization at 30 and 60 days compared to Vicryl Woven Mesh. There was no significant difference between AlloDerm and Surgisis with respect to collagen deposition and organization. Surgisis and AlloDerm showed a significantly greater amount (p < 0.05) of neovascularization than Vicryl Woven Mesh at both time points. In addition, Surgisis had a significantly greater amount (p < 0.05) of neovascularization than AlloDerm at both 30 and 60 days. CONCLUSION: Surgisis has increased baseline tensile strength compared to Vicryl Woven Mesh. Tensile strength in Vicryl Woven Mesh is equal to biosynthetic grafts after tissue incorporation. Biosynthetic grafts showed superior collagen deposition and organization. Surgisis mesh showed increased neovascularization over both AlloDerm and Vicryl Woven Mesh.

Permacol (porcine dermal collagen) and Alloderm (acellular cadaveric dermis) as a vascular patch repair for common carotid arteriotomy in a rabbit model.

Occult injuries to arteries are common in trauma and evolution of their repair has been observed throughout military conflicts. Currently, autogenous vein and polytetrafluoroethylene (PTFE) are used as patch agents for arterial trauma. However, suitable vein is often lacking in multitrauma patients, and PTFE is prone to infection in the contaminated combat wound. The purpose of this study is to evaluate Permacol, porcine dermal collagen, and Alloderm, acellular cadaveric dermis, as suitable alternatives to PTFE with the potential benefit of being used in contaminated wounds. A New Zealand White rabbit common carotid arteriotomy model was used to compare Permacol (n = 12), Alloderm (n = 11), and PTFE (n = 13) for patch repair. Thrombin generation was examined using an enzyme-linked immunosorbent assay for thrombin-antithrombin complex. Histological samples were taken to analyze vessel lumen area, vessel diameter, intimal thickness, and medial thickness. Pathological examinations were made to compare rates of intimal hyperplasia, aneurysm, patency, and thrombus formation. The Permacol group showed equivalent rates of thrombus, aneurysm, and patency compared with PTFE. Increased lumen area was seen in the Permacol group, 0.344 mm2 (p = 0.02) compared with the PTFE group, 0.204 mm2. Permacol also had decreased incidence of intimal hyperplasia compared with PTFE, 50.0% versus 92% (p < 0.05). Alloderm had increased rates of aneurysm formation, 63.6% (p = 0.004) compared with PTFE, 0.0%, and Permacol groups, 8.3%. Alloderm also had increased intimal thickness through the patch, 0.076 mm (p = 0.18), compared with PTFE, 0.026 mm, and Permacol groups, 0.024 mm. Vessel diameter through the patch showed the Alloderm group, 1.87 mm (p = 0.004), was significantly larger than both the Permacol, 1.41 mm, and PTFE groups, 1.28 mm. Furthermore, Alloderm showed leukocyte migration around the patch. Enzyme-linked immunosorbent assay for thrombin-antithrombin complex was only elevated for PTFE in the 7-day postoperative measurement but was not statistically different from the other groups. Permacol has characteristics to be an effective alternative for PTFE for patch arteriotomy repair in our rabbit model. Futher studies need to be conducted to investigate the potential of Permacol in vascular trauma. Alloderm is not a suitable alternative to PTFE for patch arteriotomy repair.

Evaluation of the effect of sildenafil and vascular endothelium growth factor combination treatment on skin flap survival in rats.

BACKGROUND: Distal ischemic necrosis of surgical flaps remains a challenging problem for the reconstructive surgeon. Recent studies have shown that either sildenafil or vascular endothelium growth factor (VEGF) treatment significantly improves ischemic skin flap viability. In this study, the effect of the combination of sildenafil and VEGF165 was evaluated on a rat skin flap model using orthogonal polarization spectral imaging and histologic analysis. METHODS: Rats were assigned to either a sham (n = 31), vehicle (n = 24), sildenafil (n = 24), VEGF (n = 23), or sildenafil and VEGF combination treatment (n = 21) groups. Distances from the distal end of the flap to avascular, stasis, and normal capillary blood flow zones were determined using orthogonal polarization spectral imaging on a skin flap model. Vessel density assessment was done at 7 days post surgery. RESULTS: Imaging analysis showed significant reduction in avascular and stasis areas in sildenafil and VEGF combination-treated groups at 7 days post surgery (p < 0.05). The combination-treated group, however, was not significantly different when compared to the group treated with sildenafil only. The sildenafil-treated group showed a significant (p < 0.05) reduction in both areas at day 7 compared to the VEGF and control groups. Histologic analysis showed no significant differences in vessel density between the groups. CONCLUSION: The combination of sildenafil and VEGF decreases the extent of avascular and stasis zones in skin flaps. The skin flap improvement seen with the combination treatment was similar to the sildenafil treatment alone suggesting that enhanced flap survival was due solely to the effect of sildenafil.

Percutaneous endoscopic gastrostomy site metastasis.

Metastases to gastrostomy sites are a rare but significant complication of percutaneous endoscopic gastrotomy (PEG) placement in cancer patients. Both direct seeding and hematogenous spread have been suggested as possible mechanisms. This article outlines the incidence, presentation, pathogenesis, and management of PEG-site metastases.

Comparative safety of atorvastatin 80 mg versus 10 mg derived from analysis of 49 completed trials in 14,236 patients.

Atorvastatin has been shown to reduce coronary events and revascularization procedures in patients with multiple risk factors for coronary heart disease. Recent studies with atorvastatin 80 mg support the overall safety of this dose during long-term treatment. However, physicians appear reluctant to use high doses of statins. A retrospective analysis of pooled data from 49 clinical trials of atorvastatin in 14,236 patients treated for an average period of 2 weeks to 52 months was conducted. The study compared the safety of atorvastatin 10 mg (n = 7,258), atorvastatin 80 mg (n = 4,798), and placebo (n = 2,180) and included analyses on treatment-associated adverse events; nonserious and serious adverse events related to the musculoskeletal, hepatic, and renal systems; the incidence of elevations of creatine kinase >10 times the upper limit of normal (ULN); and hepatic transaminases >3 times ULN. Percentages of patients experiencing > or =1 adverse event were similar across all 3 groups. Withdrawals due to treatment-related adverse events were observed in 2.4%, 1.8%, and 1.2% of patients in the atorvastatin 10 mg, atorvastatin 80 mg, and placebo groups, respectively. Serious adverse events were rare and seldom led to treatment withdrawal with any dose. Treatment-associated myalgia was observed in 1.4%, 1.5%, and 0.7% of patients in the atorvastatin 10 mg, atorvastatin 80 mg, and placebo groups, respectively. No cases of rhabdomyolysis were reported in any group. Persistent elevations in hepatic transaminases >3 times ULN were observed in 0.1%, 0.6%, and 0.2% of patients in the atorvastatin 10 mg, atorvastatin 80 mg, and placebo groups, respectively. The incidence of treatment-associated adverse events for atorvastatin 80 mg was similar to that of atorvastatin 10 mg and placebo. In conclusion, the results of this analysis support the positive safety profile of atorvastatin at the highest dose.

High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial.

CONTEXT: Evidence suggests that more intensive lowering of low-density lipoprotein cholesterol (LDL-C) than is commonly applied clinically will provide further benefit in stable coronary artery disease. OBJECTIVE: To compare the effects of 2 strategies of lipid lowering on the risk of cardiovascular disease among patients with a previous myocardial infarction (MI). DESIGN, SETTING, AND PARTICIPANTS: The IDEAL study, a prospective, randomized, open-label, blinded end-point evaluation trial conducted at 190 ambulatory cardiology care and specialist practices in northern Europe between March 1999 and March 2005 with a median follow-up of 4.8 years, which enrolled 8888 patients aged 80 years or younger with a history of acute MI. INTERVENTIONS: Patients were randomly assigned to receive a high dose of atorvastatin (80 mg/d; n = 4439), or usual-dose simvastatin (20 mg/d; n = 4449). MAIN OUTCOME MEASURE: Occurrence of a major coronary event, defined as coronary death, confirmed nonfatal acute MI, or cardiac arrest with resuscitation. RESULTS: During treatment, mean LDL-C levels were 104 (SE, 0.3) mg/dL in the simvastatin group and 81 (SE, 0.3) mg/dL in the atorvastatin group. A major coronary event occurred in 463 simvastatin patients (10.4%) and in 411 atorvastatin patients (9.3%) (hazard ratio [HR], 0.89; 95% CI, 0.78-1.01; P = .07). Nonfatal acute MI occurred in 321 (7.2%) and 267 (6.0%) in the 2 groups (HR, 0.83; 95% CI, 0.71-0.98; P = .02), but no differences were seen in the 2 other components of the primary end point. Major cardiovascular events occurred in 608 and 533 in the 2 groups, respectively (HR, 0.87; 95% CI, 0.77-0.98; P = .02). Occurrence of any coronary event was reported in 1059 simvastatin and 898 atorvastatin patients (HR, 0.84; 95% CI, 0.76-0.91; P<.001). Noncardiovascular death occurred in 156 (3.5%) and 143 (3.2%) in the 2 groups (HR, 0.92; 95% CI, 0.73-1.15; P = .47). Death from any cause occurred in 374 (8.4%) in the simvastatin group and 366 (8.2%) in the atorvastatin group (HR, 0.98; 95% CI, 0.85-1.13; P = .81). Patients in the atorvastatin group had higher rates of drug discontinuation due to nonserious adverse events; transaminase elevation resulted in 43 (1.0%) vs 5 (0.1%) withdrawals (P<.001). Serious myopathy and rhabdomyolysis were rare in both groups. CONCLUSIONS: In this study of patients with previous MI, intensive lowering of LDL-C did not result in a significant reduction in the primary outcome of major coronary events, but did reduce the risk of other composite secondary end points and nonfatal acute MI. There were no differences in cardiovascular or all-cause mortality. Patients with MI may benefit from intensive lowering of LDL-C without an increase in noncardiovascular mortality or other serious adverse reactions.Trial Registration ClinicalTrials.gov Identifier: NCT00159835.

Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease.

BACKGROUND: Recent trials have demonstrated better outcomes with intensive than with moderate statin treatment. Intensive treatment produced greater reductions in both low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP), suggesting a relationship between these two biomarkers and disease progression. METHODS: We performed intravascular ultrasonography in 502 patients with angiographically documented coronary disease. Patients were randomly assigned to receive moderate treatment (40 mg of pravastatin orally per day) or intensive treatment (80 mg of atorvastatin orally per day). Ultrasonography was repeated after 18 months to measure the progression of atherosclerosis. Lipoprotein and CRP levels were measured at baseline and follow-up. RESULTS: In the group as a whole, the mean LDL cholesterol level was reduced from 150.2 mg per deciliter (3.88 mmol per liter) at baseline to 94.5 mg per deciliter (2.44 mmol per liter) at 18 months (P<0.001), and the geometric mean CRP level decreased from 2.9 to 2.3 mg per liter (P<0.001). The correlation between the reduction in LDL cholesterol levels and that in CRP levels was weak but significant in the group as a whole (r=0.13, P=0.005), but not in either treatment group alone. In univariate analyses, the percent change in the levels of LDL cholesterol, CRP, apolipoprotein B-100, and non-high-density lipoprotein cholesterol were related to the rate of progression of atherosclerosis. After adjustment for the reduction in these lipid levels, the decrease in CRP levels was independently and significantly correlated with the rate of progression. Patients with reductions in both LDL cholesterol and CRP that were greater than the median had significantly slower rates of progression than patients with reductions in both biomarkers that were less than the median (P=0.001). CONCLUSIONS: For patients with coronary artery disease, the reduced rate of progression of atherosclerosis associated with intensive statin treatment, as compared with moderate statin treatment, is significantly related to greater reductions in the levels of both atherogenic lipoproteins and CRP.