Pectoralis muscle area and mortality in smokers without airflow obstruction.

BACKGROUND: Low muscle mass is associated with increased mortality in the general population but its prognostic value in at-risk smokers, those without expiratory airflow obstruction, is unknown. We aimed to test the hypothesis that reduced muscle mass is associated with increased mortality in at-risk smokers. METHODS: Measures of both pectoralis and paravertebral erector spinae muscle cross-sectional area (PMA and PVMA, respectively) as well as emphysema on chest computed tomography (CT) scans were performed in 3705 current and former at-risk smokers (≥10 pack-years) aged 45-80 years enrolled into the COPDGene Study between 2008 and 2013. Vital status was ascertained through death certificate. The association between low muscle mass and mortality was assessed using Cox regression analysis. RESULTS: During a median of 6.5 years of follow-up, 212 (5.7%) at-risk smokers died. At-risk smokers in the lowest (vs. highest) sex-specific quartile of PMA but not PVMA had 84% higher risk of death in adjusted models for demographics, smoking, dyspnea, comorbidities, exercise capacity, lung function, emphysema on CT, and coronary artery calcium content (hazard ratio [HR] 1.85 95% Confidence interval [1.14-3.00] P = 0.01). Results were consistent when the PMA index (PMA/height2) was used instead of quartiles. The association between PMA and death was modified by smoking status (P = 0.04). Current smokers had a significantly increased risk of death (lowest vs. highest PMA quartile, HR 2.25 [1.25-4.03] P = 0.007) while former smokers did not. CONCLUSIONS: Low muscle mass as measured on chest CT scans is associated with increased mortality in current smokers without airflow obstruction. TRIAL REGISTRATION: NCT00608764.

Bronchoarterial ratio in never-smokers adults: Implications for bronchial dilation definition.

BACKGROUND AND OBJECTIVE: Bronchiectasis manifests as recurrent respiratory infections and reduced lung function. Airway dilation, which is measured as the ratio of the diameters of the bronchial lumen (B) and adjacent pulmonary artery (A), is a defining radiological feature of bronchiectasis. A challenge to equating the bronchoarterial (BA) ratio to disease severity is that the diameters of airway and vessel in health are not established. We sought to explore the variability of BA ratio in never-smokers without pulmonary disease and its associations with lung function. METHODS: Objective measurements of the BA ratio on volumetric computed tomography (CT) scans and pulmonary function data were collected in 106 never-smokers. The BA ratio was measured in the right upper lobe apical bronchus (RB1) and the right lower lobe basal posterior bronchus. The association between the BA ratio and forced expiratory volume in 1 s (FEV1 ) was assessed using regression analysis. RESULTS: The BA ratio was 0.79 ± 0.16 and was smaller in more peripheral RB1 bronchi (P < 0.0001). The BA ratio was >1, a typical threshold for bronchiectasis, in 10 (8.5%) subjects. Subjects with a BA ratio >1 versus ≤1 had smaller artery diameters (P < 0.0001) but not significantly larger bronchial lumens. After adjusting for age, gender, race and height, the BA ratio was directly related to FEV1 (P = 0.0007). CONCLUSION: In never-smokers, the BA ratio varies by airway generation and is associated with lung function. A BA ratio >1 is driven by small arteries. Using artery diameter as reference to define bronchial dilation seems inappropriate.

Sequence conservation of the region targeted by the Abbott RealTime HBV viral load assay in clinical specimens.

The Abbott RealTime HBV assay targets the N-terminal region of the S gene. Here we analyzed the sequence variability of the assay target region from >2,100 clinical specimens. Thermodynamic modeling of the percentage of bound primer/probe at the assay annealing temperature was performed to assess the potential effect of sequence variability.

A Single-Blind, Randomized, Placebo Controlled Study to Evaluate the Benefits and Safety of Endourage Targeted Wellness Formula C Sublingual +Drops in People with Post-Acute Coronavirus Disease 2019 Syndrome.

Introduction: Coronavirus Disease 2019 (COVID-19) causes a wide range of symptoms, including death. As persons recover, some continue to experience symptoms described as Post-Acute COVID-19 Syndrome (PACS). The objectives of this study were to measure the efficacy of Formula C™, a cannabidiol (CBD)-rich, whole-flower terpene-rich preparation in managing PACS symptoms. Materials and Methods: This randomized, placebo-controlled, single-blind, open-label crossover study was conducted in 2021. Informed consent was obtained from participants, and they were randomized to two treatment groups. Group 1 (n=15) received blinded active product for 28 days, and Group 2 (n=16) received blinded placebo for 28 days (Treatment Period 1). Both groups crossed over to open-label active product for 28 days (Treatment Period 2) with a safety assessment at day 70. Patient-Reported Outcomes Measurement Information System (PROMIS®) scores and the Patient Global Impression of Change (PGIC) score were used to assess primary and secondary objectives. Safety assessments were also done at each visit. Results: Twenty-four participants completed study, with 8 withdrawals, none related to study product. PGIC and PROMIS scores improved across both groups at day 28. This raised questions about the placebo. A reanalysis of the placebo confirmed absence of CBD and unexpected medical concentration of terpenes. The study continued despite no longer having a true placebo. The improved scores on outcome measures were maintained across the open label treatment period. There were no safety events reported throughout the study. Discussion: For persons with PACS who are nonresponsive to conventional therapies, this study demonstrated symptom improvement for participants utilizing Formula C. In addition, the benefits seen in Group 2 suggest the possibility that non-CBD formulations rich in antioxidants, omega-3, and omega-6 fatty acids, gamma-linoleic acid, and terpenes may also have contributed to the overall improvement of the partial active group through the study. Conclusion: Given that both groups demonstrated improvement, both formulations may be contributing to these findings. Limitations include the small number of participants, the lack of a true placebo, and limited time on study products. Additional studies are warranted to explore both CBD-rich hemp products and hempseed oil as treatment options for PACS. Trial Registration ClinicalTrials.gov Identifier: NCT04828668.

Performance of the Abbott RealTime HIV-1 viral load assay is not impacted by integrase inhibitor resistance-associated mutations.

The Abbott RealTime HIV-1 viral load assay uses primers and probes targeted to integrase, which is also the target of integrase inhibitors such as raltegravir. Viral loads of 42 raltegravir-susceptible and 40 raltegravir-resistant specimens were determined using RealTime HIV-1 and Roche Monitor (v1.5). The differences in viral load measurements between assays were comparable in the two groups, demonstrating that the RealTime HIV-1 assay can tolerate raltegravir-selected mutations.

Prevalence, mutation patterns, and effects on protease inhibitor susceptibility of the L76V mutation in HIV-1 protease.

Patterns of HIV-1 protease inhibitor (PI) resistance-associated mutations (RAMs) and effects on PI susceptibility associated with the L76V mutation were studied in a large database. Of 20,501 sequences with ≥1 PI RAM, 3.2% contained L76V; L76V was alone in 0.04%. Common partner mutations included M46I, I54V, V82A, I84V, and L90M. L76V was associated with a 2- to 6-fold decrease in susceptibility to lopinavir, darunavir, amprenavir, and indinavir and a 7- to 8-fold increase in susceptibility to atazanavir and saquinavir.

Multiorgan structures detection using deep convolutional neural networks.

Many automatic image analysis algorithms in medical imaging require a good initialization to work properly. A similar problem occurs in many imaging-based clinical workflows, which depend on anatomical landmarks. The localization of anatomic structures based on a defined context provides with a solution to that problem, which turns out to be more challenging in medical imaging where labeled images are difficult to obtain. We propose a two-stage process to detect and regress 2D bounding boxes of predefined anatomical structures based on a 2D surrounding context. First, we use a deep convolutional neural network (DCNN) architecture to detect the optimal slice where an anatomical structure is present, based on relevant landmark features. After this detection, we employ a similar architecture to perform a 2D regression with the aim of proposing a bounding box where the structure is encompassed. We trained and tested our system for 57 anatomical structures defined in axial, sagittal and coronal planes with a dataset of 504 labeled Computed Tomography (CT) scans. We compared our method with a well-known object detection algorithm (Viola Jones) and with the inter-rater error for two human experts. Despite the relatively small number of scans and the exhaustive number of structures analyzed, our method obtained promising and consistent results, which proves our architecture very generalizable to other anatomical structures.

Differences in Respiratory Symptoms and Lung Structure Between Hispanic and Non-Hispanic White Smokers: A Comparative Study.

Background: Prior studies have demonstrated that U.S. Hispanic smokers have a lower risk of decline in lung function and chronic obstructive pulmonary disease (COPD) compared with non-Hispanic whites (NHW). This suggests there might be racial-ethnic differences in susceptibility in cigarette smoke-induced respiratory symptoms, lung parenchymal destruction, and airway and vascular disease, as well as in extra-pulmonary manifestations of COPD. Therefore, we aimed to explore respiratory symptoms, lung function, and pulmonary and extra-pulmonary structural changes in Hispanic and NHW smokers. Methods: We compared respiratory symptoms, lung function, and computed tomography (CT) measures of emphysema-like tissue, airway disease, the branching generation number (BGN) to reach a 2-mm-lumen-diameter airway, and vascular pruning as well as muscle and fat mass between 39 Hispanic and 39 sex-, age- and smoking exposure-matched NHW smokers. Results: Hispanic smokers had higher odds of dyspnea than NHW after adjustment for COPD and asthma statuses (odds ratio[OR] = 2.96; 95% confidence interval [CI] 1.09-8.04), but no significant differences were found in lung function and CT measurements. Conclusions: While lung function and CT measures of the lung structure were similar, dyspnea is reported more frequently by Hispanic than matched-NHW smokers. It seems to be an impossible puzzle but it's easy to solve a Rubik' Cube using a few algorithms.

Quantitative CT Measures of Bronchiectasis in Smokers.

BACKGROUND: Bronchiectasis is frequent in smokers with COPD; however, there are only limited data on objective assessments of this process. The objective was to assess bronchovascular morphology, calculate the ratio of the diameters of bronchial lumen and adjacent artery (BA ratio), and identify those measurements able to discriminate bronchiectasis. METHODS: We collected quantitative CT (QCT) measures of BA ratios, peak wall attenuation, wall thickness (WT), wall area, and wall area percent (WA%) at matched fourth through sixth airway generations in 21 ever smokers with bronchiectasis (cases) and 21 never-smoking control patients (control airways). In cases, measurements were collected at both bronchiectatic and nonbronchiectatic airways. Logistic analysis and the area under receiver operating characteristic curve (AUC) were used to assess the predictive ability of QCT measurements for bronchiectasis. RESULTS: The whole-lung and fourth through sixth airway generation BA ratio, WT, and WA% were significantly greater in bronchiectasis cases than control patients. The AUCs for the BA ratio to predict bronchiectasis ranged from 0.90 (whole lung) to 0.79 (fourth-generation). AUCs for WT and WA% ranged from 0.72 to 0.75 and from 0.71 to 0.75. The artery diameters but not bronchial diameters were smaller in bronchiectatic than both nonbronchiectatic and control airways (P < .01 for both). CONCLUSIONS: Smoking-related increases in the BA ratio appear to be driven by reductions in vascular caliber. QCT measures of BA ratio, WT, and WA% may be useful to objectively identify and quantify bronchiectasis in smokers. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.

Immune mechanisms in HIV infection.

Recent advances in immunobiology have led to a greater understanding of the healthy immune system and the complex pathogenesis of human immunodeficiency virus (HIV) infection. Knowledge of the mechanisms underlying the decrease in CD4+ T cells is rapidly evolving as a result of new assays, genetic advances, and recombinant DNA technologies. Studying the immune responses of long-term non-progressors is also providing insight into the immunopathology of HIV. Trials using highly active antiretroviral therapy and immune modulators have shown that it may be possible to reverse damage to the immune system and increase CD4+ T-cell numbers. Current and future findings might provide the knowledge necessary to identify effective HIV drugs and vaccines with acceptable toxicity profiles and to determine whether it will be possible to fully restore immune system function in patients with HIV disease.

Minimal sequence variability of the region of HIV-1 integrase targeted by the Abbott RealTime HIV-1 viral load assay in clinical specimens with reduced susceptibility to raltegravir.

The Abbott RealTime (ART) HIV-1 assay targets the integrase region and is designed to tolerate mismatches. Variability in integrase sequences comprising the assay target regions from >1000 clinical specimens submitted for phenotypic and genotypic raltegravir resistance testing were analyzed. In this large collection of sequences from clinical specimens, the number and location of raltegravir resistance associated mutations did not differ from those tested previously and shown not to result in under-estimation of viral loads.

Prevalence of drug-resistant HIV type 1 at the time of initiation of antiretroviral therapy in Portland, Oregon.

The presence of transmitted drug-resistant HIV-1 (TDR) at the time of antiretroviral therapy (ART) initiation is associated with failure to achieve viral load suppression. Rates of TDR in ART-naive patients have been reported from various parts of the world through ongoing national, regional, and global evaluations; however, surveillance of TDR in Portland, Oregon has not been previously described. We describe the prevalence of TDR in patients in the Portland area who have recently entered care. Genotypic data were obtained from plasma specimens collected between 2003 and 2009 from 165 recently identified HIV-1-positive, ART-naive adults in care at the Multnomah County Health Department. Median time from diagnosis to first genotype was 2.7 months. Mutations associated with TDR were observed in 33 (20.0%) patients. Mutations associated with resistance to nucleoside reverse transcriptase (RT) inhibitors (NRTI), nonnucleoside RT inhibitors (NNRTI), and protease inhibitors (PI) were found in 15 (9.1%), 17 (10.3%), and 5 (3.0%) patients, respectively (p=0.013 for NNRTI vs. PI, and 0.035 for NRTI vs. PI, Fisher exact test). Dual class resistance was observed in four (2.4%) patients. Predominant RT mutations included M41L, T215C or S, and K103N. The prevalence of HIV-1 with NRTI resistance-associated mutations increased from 2006 to 2008-2009 (p=0.004) based on date of diagnosis. These data indicate relatively high rates of drug resistance present prior to ART initiation among patients in the Portland area, and support continued surveillance of local trends of TDR to inform optimal individual treatment strategies and public health decisions.