Effect of Weight Loss and Continuous Positive Airway Pressure on Obstructive Sleep Apnea and Metabolic Profile Stratified by Craniofacial Phenotype: A Randomized Clinical Trial.

Rationale: Craniofacial structure is believed to modulate the effect of weight loss on obstructive sleep apnea (OSA), but whether this affects metabolic profile after weight loss compared with continuous positive airway pressure (CPAP) is unknown among obese Chinese patients with OSA. Objectives: To compare the change in metabolic profile between a lifestyle modification program (LMP), stratified by craniofacial phenotype, and CPAP therapy for 6 months. Methods: We randomly assigned 194 patients with body mass index ⩾ 25 kg/m2 and moderate to severe OSA to participate in the LMP or receive CPAP therapy for 6 months in a 2:1 ratio. Assessments included computed tomography for assessing maxillomandibular volume (MMV), hsCRP (high-sensitivity C-reactive protein), and insulin sensitivity. Measurements and Main Results: Among 128 and 66 subjects in the LMP and CPAP groups, respectively, hsCRP was reduced more in the LMP group than the CPAP group (median [interquartile range], -0.7 [-1.4 to -0.0] vs. -0.3 [-0.9 to 0.4] mg/L; P = 0.012). More patients in the LMP group achieved low hsCRP (<1 mg/L) than the CPAP group (21.1% vs. 9.1%; P = 0.04). Insulin sensitivity improved only in the LMP group, with 3.1 (95% confidence interval, 1.5-6.6) times more patients with normal glucose regulation after intervention. The LMP group was stratified into LMP-small MMV (n = 64) and LMP-large MMV (n = 64) groups according to the median MMV value of 233.2 cm3. There was no significant difference in hsCRP (median [interquartile range], -0.7 [-1.3 to 0.1] vs. -0.7 [-1.5 to -0.2] mg/L; P = 0.884) and insulin sensitivity (median [interquartile range], 0.5 [-0.2 to 1.9] vs. 0.6 [0.1 to 2.0]; P = 0.4860) between the LMP-small MMV and LMP-large MMV groups. Conclusions: Weight reduction alleviated subclinical inflammation and improved insulin sensitivity more than CPAP among obese Chinese patients with moderate to severe OSA, and this effect was not influenced by craniofacial structure. Clinical trial registered with www.clinicaltrials.gov (NCT03287973).

The Magnetic Resonance Imaging in Active Surveillance (MRIAS) Trial: Use of Baseline Multiparametric Magnetic Resonance Imaging and Saturation Biopsy to Reduce the Frequency of Surveillance Prostate Biopsies.

PURPOSE: Prospective studies are lacking in assessing the diagnostic utility of serial multiparametric magnetic resonance imaging to predict biopsy proven progression to clinically significant prostate cancer in men on active surveillance, as well as the oncologic safety of baseline magnetic resonance imaging and saturation diagnostic biopsy in replacing early confirmatory biopsy during active surveillance. MATERIALS AND METHODS: A total of 172 men were enrolled in this single arm prospective trial. Men with cT2 or lower histologically proven prostate cancer (Gleason 3+3=6 or Gleason 3+4=7 with 10% or less Gleason pattern 4 overall and less than 2 cores Gleason pattern 4) eligible for surveillance were included in the study. Men underwent baseline multiparametric magnetic resonance imaging and saturation biopsy followed by serial annual multiparametric magnetic resonance imaging until a 3-year end point per protocol saturation biopsy. The standardized 1-year confirmatory biopsy was omitted and biopsies during the protocol were triggered based on new abnormalities on multiparametric magnetic resonance imaging and prostate specific antigen density. RESULTS: We report the prespecified interim analysis of the first 100 men at 3 years. At baseline the median age was 64.5 (IQR 57.25-69) years, prostate specific antigen was 4.7 ng/ml (IQR 3.4-6.6), 91% had Gleason 3+3=6 prostate cancer and multiparametric magnetic resonance imaging was negative (Prostate Imaging Reporting and Data System 1/2/3) in 87% of men. Within 3 years 21% experienced pathological progression. The positive predictive value, negative predictive value, sensitivity and specificity for detection of clinically significant prostate cancer by surveillance multiparametric magnetic resonance imaging was 45%, 89%, 61% and 80%, respectively. Positive surveillance magnetic resonance imaging (p=0.002) and prostate specific antigen density greater than 0.2 ng/ml (p=0.042) had significant predictive value for clinically significant prostate cancer. CONCLUSIONS: Our novel active surveillance protocol incorporating multiparametric magnetic resonance imaging detected most cases of disease progression and may enable confirmatory biopsy to be deferred, but should not replace 3-year surveillance biopsy altogether due to occasional magnetic resonance imaging invisible tumors.

Percutaneous Portal Vein Embolization Using a Simplified Sheathless 18-Gauge Trocar Needle Approach: Review of Efficacy and Safety.

PURPOSE: Portal vein (PV) embolization (PVE) is traditionally performed via a PV sheath with selective embolization of PV branches. Here, the efficacy and safety of PVE with the use of only an 18-gauge needle is reported. MATERIALS AND METHODS: Consecutive patients who underwent PVE from 2009 through 2017 were retrospectively reviewed. Forty-five patients (mean age, 60 y ± 7.6; 38 men) underwent 45 PVE procedures. Hepatocellular carcinoma, cholangiocarcinoma, and metastases accounted for 26 (58%), 13 (29%), and 6 (13%) patients, respectively. PVE was performed by puncturing a branch of right PV with an 18-gauge needle under US guidance. Via the same needle, direct portography was performed, followed by PVE with an N-butyl cyanoacrylate/Lipiodol mixture. Percentage increase of future liver remnant (FLR) volume and increase in ratio of FLR to total liver volume were estimated as measures of efficacy. Complications were reported according to Society of Interventional Radiology classification. Fluoroscopy time, procedure time, and dose-area product (DAP) were recorded. RESULTS: Technical success rate was 100%. The median DAP, fluoroscopy time, and procedure time were 74,387 mGy·cm2 (IQR, 90,349 mGy·cm2), 3.5 min (IQR, 2.10 min), and 24 min (IQR, 10.5 min). Among the 23 patients with complete CT volumetry data, mean increase in the ratio of FLR to total liver volume and percentage increase of FLR volume were 12.5% ± 7.7 and 50% ± 33, respectively. There were 3 minor complications (asymptomatic nonocclusive emboli in FLR) and 3 major complications (1 hepatic vein emboli, 1 subphrenic collection, and 1 hepatic infarct). CONCLUSIONS: PVE via a sheathless 18-gauge needle approach is feasible, with satisfactory FLR hypertrophy.

Thickness-to-Height Ratio of Intravesical Prostatic Protrusion Predicts the Clinical Outcome and Morbidity of Prostatic Artery Embolization for Benign Prostatic Hyperplasia.

PURPOSE: To evaluate the presence of intravesical prostatic protrusion (IPP) and its thickness-to-height (T/H) ratio as a predictor for the clinical outcome and morbidity of prostatic artery embolization (PAE) for benign prostatic hyperplasia. MATERIALS AND METHODS: This was a prospective, single-center, institutional review board-approved study from June 2015 to December 2018 of 82 consecutive patients (age, 53-79 years; median, 66 years) with International Prostate Symptom Score (IPSS) ≥15 and quality-of-life (QOL) score ≥3. The presence of IPP and its T/H ratio were assessed on baseline magnetic resonance imaging for their correlation with the clinical outcomes of suboptimal IPSS (IPSS ≥10) and suboptimal QOL (QOL ≥3) up to 12 months after PAE and the occurrence of post-procedure complications (≤30 days), which caused a certain degree of urinary outflow obstruction. The chi-squared test was used for analysis. RESULTS: IPP was present in 57 of 82 patients (69.5%). The presence of IPP correlated with the occurrence of post-procedure complications (P = .009) but not with suboptimal IPSS at 12 months (P = .758). IPP with a T/H ratio ≤1.3 correlated with suboptimal IPSS at 12 months (P = .025) and suboptimal QOL at 6 months (P = .025) and 12 months (P = .008), as well as with the occurrence of post-procedure complications (P = .009). CONCLUSIONS: IPP with a T/H ratio ≤1.3 predicted the occurrence of post-procedure complications with urinary obstruction. A T/H ratio ≤1.3 but not the presence of IPP alone predicted the clinical outcome up to 12 months after PAE.

Incidental LAD stenosis identified on non-gated chest CTA.

A 57-year-old male former smoker presented to the Emergency Department (ED) with blurry vision, headache, and generalized weakness. He was hypoxic on room air and ECG showed sinus tachycardia. A CT pulmonary angiogram was ordered in the ED and revealed no pulmonary embolism but incidentally noted a likely significant stenosis in the proximal LAD. Subsequent cardiac catheterization revealed a 90% stenotic lesion with percutaneous coronary intervention leading to symptom resolution. Unlike coronary CTA, CTPA is performed with non-ECG gated helical scanning and generates motion artifacts associated with myocardial contraction. However, the timing of vascular contrast opacification during CTPA often allows for at least partial evaluation of the coronary arteries, especially ostial and proximal segments. Physicians ordering and evaluating noncardiac-focused CT chest studies, particularly in the ED, should remain cognizant of the radiographic appearance of underlying CAD, particularly life-threatening incidental coronary pathologies to allow for timely management and intervention.

Measurement variability of blood-brain barrier permeability using dynamic contrast-enhanced magnetic resonance imaging.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is used to quantify the blood-brain barrier (BBB) permeability-surface area product. Serial measurements can indicate changes in BBB health, of interest to the study of normal physiology, neurological disease, and the effect of therapeutics. We performed a scan-rescan study to inform both sample size calculation for future studies and an appropriate reference change value for patient care. The final dataset included 28 healthy individuals (mean age 53.0 years, 82% female) scanned twice with mean interval 9.9 weeks. DCE-MRI was performed at 3T using a 3D gradient echo sequence with whole brain coverage, T1 mapping using variable flip angles, and a 16-min dynamic sequence with a 3.2-s time resolution. Segmentation of white and grey matter (WM/GM) was performed using a 3D magnetization-prepared gradient echo image. The influx constant Ki was calculated using the Patlak method. The primary outcome was the within-subject coefficient of variation (CV) of Ki in both WM and GM. Ki values followed biological expectations in relation to known GM/WM differences in cerebral blood volume (CBV) and consequently vascular surface area. Subject-derived arterial input functions showed marked within-subject variability which were significantly reduced by using a venous input function (CV of area under the curve 46 vs. 12%, p < 0.001). Use of the venous input function significantly improved the CV of Ki in both WM (30 vs. 59%, p < 0.001) and GM (21 vs. 53%, p < 0.001). Further improvement was obtained using motion correction, scaling the venous input function by the artery, and using the median rather than the mean of individual voxel data. The final method gave CV of 27% and 17% in WM and GM, respectively. No further improvement was obtained by replacing the subject-derived input function by one standard population input function. CV of Ki was shown to be highly sensitive to dynamic sequence duration, with shorter measurement periods giving marked deterioration especially in WM. In conclusion, measurement variability of 3D brain DCE-MRI is sensitive to analysis method and a large precision improvement is obtained using a venous input function.

Complex cardiac implantable electronic device infections in Alberta, Canada: An epidemiologic cohort study of validated administrative data.

OBJECTIVE: To establish the epidemiology of cardiac implantable electronic device (CIED) infections in Alberta, Canada, using validated administrative data. DESIGN: Retrospective, population-based cohort study. SETTING: Alberta Health Services is a province-wide health system that services all of Alberta, Canada. PARTICIPANTS: Adult patients who underwent first-time CIED implantation or generator replacement in Alberta, Canada, between January 1, 2011, and December 31, 2019. METHODS: CIED implant patients were identified from the Paceart database. Patients who developed an infection within 1 year of the index procedure were identified through validated administrative data (International Classification of Diseases, Tenth Revision in Canada). Demographic characteristics of patients were summarized. Logistic regression models were used to analyze device type, comorbidities, and demographics associated with infection rates and mortality. RESULTS: Among 27,830 CIED implants, there were 205 infections (0.74%). Having 2 or more comorbidities was associated with higher infection risk. Generator replacement procedures (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.34-0.84; P = .008), age increase of every 10 years (OR, 0.73; 95% CI, 0.66-0.82; P ≤ .001), and index procedure after 2014 were associated with decreased risk. Comparing the infected to uninfected groups, the hospitalization rates were 2.63 compared to 0.69, and the mortality rates were 10.73% compared to 3.49%, respectively (P < .001). CONCLUSIONS: There is a slightly lower overall rate of CIED infections Alberta, Canada compared to previously described epidemiology. Implants after 2014, and generator replacements showed a decreased burden of infection. Patients with younger age, and 2 or more comorbidities are at greatest risk of CIED infection. The burden of hospitalization and mortality is substantially higher in infected patients.

Perturbations in common and distinct inflammatory pathways associated with morning and evening fatigue in outpatients receiving chemotherapy.

BACKGROUND: Moderate to severe fatigue occurs in up to 94% of patients with cancer. Recent evidence suggests that morning and evening fatigue are distinct dimensions of physical fatigue. The purposes of this study were to evaluate the transcriptome for common and distinct perturbed inflammatory pathways in patients receiving chemotherapy who reported low versus high levels of morning or low versus high levels of evening cancer-related fatigue. METHODS: Patients completed questionnaires during the week prior to their chemotherapy treatment. Severity of morning and evening fatigue was evaluated using the Lee Fatigue Scale. Gene expression and pathway impact analyses (PIA) were performed in two independent samples using RNA-sequencing (n = 357) and microarray (n = 360). Patterns of interactions between and among these perturbed pathways were evaluated using a knowledge network (KN). RESULTS: Across the PIA, nine perturbed pathways (FDR < 0.025) were common to both morning and evening fatigue, six were distinct for morning fatigue, and four were distinct for evening fatigue. KN (19 nodes, 39 edges) identified the phosphatidylinositol 3-kinase (PI3K)-Akt pathway node (perturbed in evening fatigue) with the highest betweenness (0.255) and closeness (0.255) centrality indices. The next highest betweenness centrality indices were seen in pathways perturbed in evening fatigue (i.e., nuclear factor kappa B: 0.200, natural killer cell-mediated cytotoxicity: 0.178, mitogen-activated protein kinase: 0.175). CONCLUSIONS: This study describes perturbations in common and distinct inflammatory pathways associated with morning and/or evening fatigue. PI3K-Akt was identified as a bottleneck pathway. The analysis identified potential targets for therapeutic interventions for this common and devastating clinical problem.

Clinical and Economic Outcomes Associated With Remote Monitoring for Cardiac Implantable Electronic Devices: A Population-Based Analysis.

BACKGROUND: Despite expert recommendations advocating use of remote monitoring (RM) of cardiac implantable electronic devices, implementation in routine clinical practice remains modest due to inconsistent funding policies across health systems and uncertainty regarding the efficacy of RM to reduce adverse cardiovascular outcomes. METHODS: We conducted a population-based cohort study of patients with de novo implantable cardioverter-defibrillators (ICDs) with or without cardiac resynchronization therapy (CRT-D), using administrative health data in Alberta, Canada, from 2010 to 2016. We assessed RM status as a predictor of all-cause mortality and cardiovascular (CV) hospitalization using Cox proportional hazards modelling, and direct health costs by generalized linear models. From this real-world data, we then constructed a decision-analytic Markov model to estimate the projected costs and benefits associated with RM compared with in-clinic visit follow-up alone. RESULTS: Among 2799 ICD and CRT-D patients, 1830 (63.4%) were followed by RM for a mean follow-up of 50.3 months. After adjustment for age, sex, and comorbidities, RM was associated with a lower risk of death (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.36-0.52; P < 0.001) and CV hospitalization (HR 0.76, 95% CI 0.64-0.91; P = 0.002). In the economic model, cost savings were observed over 5 years with an estimated savings of $12,195 per person (95% CI -$21,818 to -$4,790). The model estimated a cost-savings associated with RM strategy in 99% of simulations. CONCLUSIONS: These population data support more widespread implementation of RM technology to facilitate better patient outcomes and improve health system efficiency.

Oncological and Quality-of-life Outcomes Following Focal Irreversible Electroporation as Primary Treatment for Localised Prostate Cancer: A Biopsy-monitored Prospective Cohort.

BACKGROUND: Focal irreversible electroporation (IRE) can be used to treat men with localised prostate cancer (PCa) with reduced impact on quality of life (QoL). OBJECTIVE: To assess oncological and functional outcomes. DESIGN, SETTING, AND PARTICIPANTS: To report on a prospective database of patients undergoing primary IRE between February 2013 and August 2018. A minimum of 12-mo follow-up was available for 123 patients. Median follow-up was 36 mo (interquartile range [IQR] 24-52 mo). A total of 112 (91%) patients had National Comprehensive Cancer Network intermediate risk and 11 (9%) had low risk. A total of 12 (9.8%) had International Society of Urological Pathology (ISUP) grade 1, 88 (71.5%) had ISUP 2, and 23 (18.7%) had ISUP 3. INTERVENTION: Focal IRE ablation of PCa lesions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Follow-up involved serial prostate-specific antigen (PSA), multiparametric magnetic resonance imaging (mpMRI), and transperineal template mapping biopsy (TTMB) at 12 mo. Failure-free survival (FFS) was defined as progression to whole-gland or systemic treatment or metastasis/death. Functional outcomes were assessed. RESULTS AND LIMITATIONS: Median age was 68yr (IQR 62-73yr). Median preoperative PSA was 5.7ng/ml (IQR 3.8-8.0ng/ml). On post-treatment TTMB, in-field recurrence was present in 2.7-9.8% of patients. FFS at 3yr was 96.75%, metastasis-free survival 99%, and overall survival 100%. A total of 18 patients required salvage treatment (12 had repeat IRE; six had whole-gland treatment). The negative predictive value of mpMRI was 94% and sensitivity 40% for detecting in-field residual disease 6 mo after treatment. Among patients who returned questionnaires, 80/81 (98.8%) remained pad free and 40/53 (76%) had no change in erectile function. CONCLUSIONS: Focal IRE in select patients with localised clinically significant PCa has satisfactory short-term oncological outcomes with a minimal impact on patient QoL. PATIENT SUMMARY: In this study, 123 patients underwent focal therapy using irreversible electroporation. Follow-up biopsy was clear of residual disease in 90.2-97.3% of patients. Of patients, 96.75% avoided whole gland treatment at 3yr.

Management of a Case of Mucor Colonization in Breast Tissue Expander Seroma Pocket.

Mucormycosis has a mortality rate reaching 90%, and is imperative that therapy be initiated rapidly once a diagnosis is made. Successful treatment consists of management of underlying risk factors, surgical debridement, and antifungal therapies. The dilemma whether or not to pursue extensive debridement presents when the wound is cultured positive but the patient is not systemically ill. We present the first reported case of successful medical treatment of a seroma pocket colonized with mucor in a patient undergoing bilateral reconstruction with tissue expander and acellular dermal matrix.

Clearance of beta-amyloid is facilitated by apolipoprotein E and circulating high-density lipoproteins in bioengineered human vessels.

Amyloid plaques, consisting of deposited beta-amyloid (Aß), are a neuropathological hallmark of Alzheimer's Disease (AD). Cerebral vessels play a major role in AD, as Aß is cleared from the brain by pathways involving the cerebrovasculature, most AD patients have cerebrovascular amyloid (cerebral amyloid angiopathy (CAA), and cardiovascular risk factors increase dementia risk. Here we present a notable advance in vascular tissue engineering by generating the first functional 3-dimensioinal model of CAA in bioengineered human vessels. We show that lipoproteins including brain (apoE) and circulating (high-density lipoprotein, HDL) synergize to facilitate Aß transport across bioengineered human cerebral vessels. These lipoproteins facilitate Aß42 transport more efficiently than Aß40, consistent with Aß40 being the primary species that accumulates in CAA. Moreover, apoE4 is less effective than apoE2 in promoting Aß transport, also consistent with the well-established role of apoE4 in Aß deposition in AD.

High-density lipoproteins suppress Aß-induced PBMC adhesion to human endothelial cells in bioengineered vessels and in monoculture.

BACKGROUND: Alzheimer's Disease (AD), characterized by accumulation of beta-amyloid (Aß) plaques in the brain, can be caused by age-related failures to clear Aß from the brain through pathways that involve the cerebrovasculature. Vascular risk factors are known to increase AD risk, but less is known about potential protective factors. We hypothesize that high-density lipoproteins (HDL) may protect against AD, as HDL have vasoprotective properties that are well described for peripheral vessels. Epidemiological studies suggest that HDL is associated with reduced AD risk, and animal model studies support a beneficial role for HDL in selectively reducing cerebrovascular amyloid deposition and neuroinflammation. However, the mechanism by which HDL may protect the cerebrovascular endothelium in the context of AD is not understood. METHODS: We used peripheral blood mononuclear cell adhesion assays in both a highly novel three dimensional (3D) biomimetic model of the human vasculature composed of primary human endothelial cells (EC) and smooth muscle cells cultured under flow conditions, as well as in monolayer cultures of ECs, to study how HDL protects ECs from the detrimental effects of Aß. RESULTS: Following Aß addition to the abluminal (brain) side of the vessel, we demonstrate that HDL circulated within the lumen attenuates monocyte adhesion to ECs in this biofidelic vascular model. The mechanism by which HDL suppresses Aß-mediated monocyte adhesion to ECs was investigated using monotypic EC cultures. We show that HDL reduces Aß-induced PBMC adhesion to ECs independent of nitric oxide (NO) production, miR-233 and changes in adhesion molecule expression. Rather, HDL acts through scavenger receptor (SR)-BI to block Aß uptake into ECs and, in cell-free assays, can maintain Aß in a soluble state. We confirm the role of SR-BI in our bioengineered human vessel. CONCLUSION: Our results define a novel activity of HDL that suppresses Aß-mediated monocyte adhesion to the cerebrovascular endothelium.

Elbow MR arthrography with traction.

OBJECTIVE: To assess the effect of axial traction during MR arthrography (MRA) of the elbow joint on joint space widening, contrast dispersion between opposing cartilage surfaces and cartilage surface visibility. METHODS: 11 patients with elbow MRA with and without axial traction were prospectively studied. Two radiologists independently measured the elbow joint space width and semi-quantitatively graded contrast material dispersion between the opposing cartilage surfaces as well as the articular cartilage surface visibility before and after traction. The detection and visibility of articular cartilage defects were also compared before and after traction. Patients were instructed to report on pain or any other symptoms during elbow traction. RESULTS: No patient reported discomfort, pain or any other symptoms related to traction on immediate and intermediate-term follow-up. Joint space width increased, more at the radiocapitellar joint space (Δ = 0.63 mm, p = 0.005) than at the ulnotrochlear joint space (Δ = 0.17 mm, p = 0.012), with contrast dispersion into the radiocapitellar joint and cartilage visibility of the radiocapitellar joint space significantly improving after traction (all p < 0.05). All of these parameters also improved at the ulnotrochlear joint, although this did not reach statistical significance. Traction improved the visibility of cartilage defects. CONCLUSION: This is the first study to evaluate the effect of traction on MRA of the elbow joint. This technique is safe and technically feasible. Traction MRA improves the cartilage surface visibility and cartilage defect visibility. ADVANCES IN KNOWLEDGE: This technique is safe and technically feasible. Traction MRA improves cartilage surface visibility and cartilage defect visibility.