DEep learning-based rapid Spiral Image REconstruction (DESIRE) for high-resolution spiral first-pass myocardial perfusion imaging

The objective of the current study was to develop and evaluate a DEep learning-based rapid Spiral Image REconstruction (DESIRE) technique for high-resolution spiral first-pass myocardial perfusion imaging with whole-heart coverage, to provide fast and accurate image reconstruction for both single-slice (SS) and simultaneous multislice (SMS) acquisitions. Three-dimensional U-Net–based image enhancement architectures were evaluated for high-resolution spiral perfusion imaging at 3 T. The SS and SMS MB = 2 networks were trained on SS perfusion images from 156 slices from 20 subjects. Structural similarity index (SSIM), peak signal-to-noise ratio (PSNR), and normalized root mean square error (NRMSE) were assessed, and prospective images were blindly graded by two experienced cardiologists (5: excellent; 1: poor). Excellent performance was demonstrated for the proposed technique. For SS, SSIM, PSNR, and NRMSE were 0.977 [0.972, 0.982], 42.113 [40.174, 43.493] dB, and 0.102 [0.080, 0.125], respectively, for the best network. For SMS MB = 2 retrospective data, SSIM, PSNR, and NRMSE were 0.961 [0.950, 0.969], 40.834 [39.619, 42.004] dB, and 0.107 [0.086, 0.133], respectively, for the best network. The image quality scores were 4.5 [4.1, 4.8], 4.5 [4.3, 4.6], 3.5 [3.3, 4], and 3.5 [3.3, 3.8] for SS DESIRE, SS L1-SPIRiT, MB = 2 DESIRE, and MB = 2 SMS-slice-L1-SPIRiT, respectively, showing no statistically significant difference (p = 1 and p = 1 for SS and SMS, respectively) between L1-SPIRiT and the proposed DESIRE technique. The network inference time was ~100 ms per dynamic perfusion series with DESIRE, while the reconstruction time of L1-SPIRiT with GPU acceleration was ~ 30 min. It was concluded that DESIRE enabled fast and high-quality image reconstruction for both SS and SMS MB = 2 whole-heart high-resolution spiral perfusion imaging.     

Chronic acidosis rewires cancer cell metabolism through PPARα signaling

The mechanisms linking tumor microenvironment acidosis to disease progression are not understood. Here, we used mammary, pancreatic, and colon cancer cells to show that adaptation to growth at an extracellular pH (pH_e) mimicking acidic tumor niches is associated with upregulated net acid extrusion capacity and elevated intracellular pH at physiological pH_e, but not at acidic pH_e. Using metabolic profiling, shotgun lipidomics, imaging and biochemical analyses, we show that the acid adaptation-induced phenotype is characterized by a shift toward oxidative metabolism, increased lipid droplet-, triacylglycerol-, peroxisome content and mitochondrial hyperfusion. Peroxisome proliferator-activated receptor-α (PPARA, PPARα) expression and activity are upregulated, at least in part by increased fatty acid uptake. PPARα upregulates genes driving increased mitochondrial and peroxisomal mass and β-oxidation capacity, including mitochondrial lipid import proteins CPT1A, CPT2 and SLC25A20, electron transport chain components, peroxisomal proteins PEX11A and ACOX1, and thioredoxin-interacting protein (TXNIP), a negative regulator of glycolysis. This endows acid-adapted cancer cells with increased capacity for utilizing fatty acids for metabolic needs, while limiting glycolysis. As a consequence, the acid-adapted cells exhibit increased sensitivity to PPARα inhibition. We conclude that PPARα is a key upstream regulator of metabolic changes favoring cancer cell survival in acidic tumor niches.     

Aspirin and nonaspirin nonsteroidal antiinflammatory drug use and occurrence of colorectal adenoma in Black American women

Evidence suggests that aspirin use reduces the occurrence of colorectal neoplasia. Few studies have investigated the association among Black Americans, who are disproportionately burdened by the disease. We assessed aspirin use in relation to colorectal adenoma among Black women. The Black Women's Health Study is a prospective cohort of self-identified Black American women established in 1995. Participants reported regular aspirin use on baseline and follow-up questionnaires. Beginning in 1999, participants reported undergoing a colonoscopy or sigmoidoscopy, the only procedures through which colorectal adenomas can be diagnosed. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between aspirin use and colorectal adenoma among 34 397 women who reported at least 1 colonoscopy or sigmoidoscopy. From 1997 through 2018, 1913 women were diagnosed with an adenoma. Compared to nonaspirin users, regular users had 14% (OR = 0.86, 95% CI: 0.78-0.95) lower odds of adenoma. The odds of adenoma decreased with increasing duration of aspirin use (≥10 years: OR = 0.80, 95% CI: 0.66-0.96). Initiating aspirin at a younger age was associated with a reduced adenoma occurrence (age < 40 years at initiation: OR = 0.69, 95% CI: 0.55-0.86). Regular aspirin use was associated with a decreased odds of colorectal adenoma in our study of Black women. These findings support evidence demonstrating a chemopreventive impact of aspirin on colorectal neoplasia and suggest that aspirin may be a useful prevention strategy among US Black women.     

One Week of Hospitalization Following Elective Hip Surgery Induces Substantial Muscle Atrophy in Older Patients

Objectives

Short successive periods of skeletal muscle disuse have been suggested to substantially contribute to the observed loss of skeletal muscle mass over the life span. Hospitalization of older individuals due to acute illness, injury, or major surgery generally results in a mean hospital stay of 5 to 7 days, during which the level of physical activity is strongly reduced. We hypothesized that hospitalization following elective total hip arthroplasty is accompanied by substantial leg muscle atrophy in older men and women.

An open-label,prospective, randomized,controlled, multicenter,phase 1b study of StrataGraft skin tissue versus autografting in patients with deep partial-thickness thermal burns

ObjectiveThis open-label, controlled, randomized study assessed the safety, tolerability, and efficacy of StrataGraft tissue compared to autograft in the treatment of deep partial-thickness (DPT) burns.MethodsThirty subjects with DPT thermal burns (3%–43% total body surface area) were treated with StrataGraft tissue as follows: cohort 1, ≤220 cm² refrigerated tissue; cohort 2, ≤440 cm² refrigerated tissue; and cohort 3, ≤440 cm² cryopreserved tissue. On each subject, two comparable areas of DPT burn were randomized to receive StrataGraft tissue or autograft. Coprimary end points were the percent area of the StrataGraft tissue treatment site undergoing salvage autografting by Day 28 and wound closure of treatment sites by 3 months.ResultsBy Day 28, no StrataGraft tissue treatment sites underwent autografting. By 3 months, 93% and 100% of the StrataGraft tissue and autograft treatment sites achieved complete wound closure, respectively. No significant differences in observer total and overall opinion POSAS scores between StrataGraft tissue and autograft treatment sites were observed at any timepoint. The most common adverse event was pruritus (17%).ConclusionsStrataGraft tissue treatment of DPT thermal burns reduced the need for autograft, resulted in wound closure and treatment-site cosmesis comparable to that of autograft, and was well tolerated.     

Parental longevity and survival among patients with multiple myeloma and monoclonal gammopathy of undetermined significance: a population-based study

Parental longevity is associated with an increased life expectancy; results with regard to specific diseases are conflicting. There are limited data focusing on host characteristics and their effect on survival among multiple myeloma (MM) patients and individuals with monoclonal gammopathy of undetermined significance (MGUS). Therefore, our aim was to evaluate the impact of parental longevity on survival of patients with MM and MGUS. A total of 4675 patients with MM, 6812 MGUS patients and 13 398 population-based controls for MM as well as 19 110 controls for MGUS, from 1988 to 2013, were included in the study. Longevity was defined as >90 years of age. Among MM patients, parental longevity was associated with a decreased risk of death [hazard ratio (HR) = 0·92, 95% confidence interval (CI) 0·84–0·99] and the same was true for MGUS patients (HR = 0·87, 95% CI 0·78–0·96). Having one long lived parent significantly decreased the risk of death in both groups, but was not statistically significant when both parents exceeded 90 years of age. In conclusion, parental longevity decreases the risk of death for patients with MM and MGUS which may reflect the importance of the host's genetic and environmental factors in relation to survival.     

Complications in Intermediate Uveitis: Prevalence,Time of Onset,and Effects on Vision in Short-Term and Long-Term Follow-Up

Purpose: To study the prevalence and time of onset of ocular complications in intermediate uveitis (IU) and to assess their effects on visual outcome in short-term and long-term follow-up.

Methods: A retrospective cohort study of patients with IU who had a minimal follow-up of one year.

Results: 96 patients (174 eyes, 70% females) were included with a mean age at presentation of 30 years. Children constituted 38% of all patients. Mean follow- up was 64.9 months. Pars planitis was the most common form followed by sarcoidosis and multiple sclerosis. Cystoid macular edema (CME), cataract, epiretinal membrane and posterior synechiae were the most prevalent complications. Posterior synechiae, band keratopathy, cataract and papillitis at presentation were associated with worse presenting visual acuity (VA). Of the late-onset complications, glaucoma/ocular hypertension (OHT) was the most significantly associated with worse long-term VA. Most sight-threatening complications (namely CME and glaucoma) were diagnosed at presentation while late complications predominantly affected the posterior segment and included among others peripheral retinal elevations, vasoproliferative tumors, and vitreous hemorrhage. Median LogMAR VA improved at short-term and long-term follow-up, from 0.2 to 0.1 (p<0.001). Subgroup analysis revealed significant VA improvement for eyes with all the different complications except for eyes with glaucoma/OHT.

Conclusion: IU is a chronic low-grade uveitis that may be associated with protean early and late complications of the anterior or posterior segments or both. Optimal treatment regimens are imperative for the strict control of inflammation and proper management of complications thus allowing a favorable long-term prognosis.