Mean Absolute Increase Research Articles

The effect of bronchoscopic lung volume reduction on the bronchodilator response.

Bronchoscopic lung volume reduction (BLVR) is a method of achieving lung collapse in severely emphysematous regions. One of the measures of success is the improvement in post-bronchodilator forced expiratory volume in the first second (FEV1). The change in bronchodilator response (BDR) following BLVR is typically not reported, however, the changes in lung physiology that accompany endobronchial valve placement may impact aerosol drug delivery and alter the response to bronchodilators. We compared the BDR before and after BLVR to evaluate this effect. We performed a retrospective study to analyze the change in BDR following BLVR. We included patients who underwent pulmonary function test (PFT) within 6 months of BLVR and confirmed complete lobar atelectasis. The pre-BLVR BDR for each patient served as the control, which was then compared to the post-BLVR BDR. The mean difference in the BDR before and after valve placement was determined. The comparison between pre- and post-BLVR means was performed using a t-test. A total of 35 patients were assessed for the study. Fifteen patients were excluded (due to valve removal, incomplete lobar collapse, and no pre- or post-BLVR PFT available). Of the 20 remaining patients, 14 had a positive BDR at baseline before BLVR. Following BLVR, 13 of the 14 patients demonstrated a non-significant increase in the BDR. The mean BDR for pre- and post-valve was 83.6 vs. 116.3 mL, respectively. The mean absolute increase in BDR following BLVR was 32.7 mL [95% confidence interval (CI): -32.5 to 97.8, P=0.31]. When including all 20 patients, the mean BDR pre- and post-BLVR was 47.5 vs. 86.5 mL, respectively, with a mean increase in BDR by 39 mL (95% CI: 22.3 to 100.3, P=0.21). BLVR may improve the BDR in patients with complete lobar atelectasis.

‘SurgTalk’: The Educational Outcomes Associated With Development of a Surgical Podcast for Undergraduate Medical Students

Educational podcast series are becoming increasingly popular as free open access medical education (FOAMed) resources, however, the educational benefit associated with their use is unclear. The aim of this study was to assess the educational outcomes associated with the implementation of a surgical podcast series for undergraduate medical students. Two conversational case-based podcast episodes were recorded covering 2 common surgical presentations. Final-year medical students were recruited prospectively in January 2023 and underwent a baseline multiple choice question (MCQ) test covering the material within the podcast episodes. Participants were then provided with the episode files through encrypted Google Drive links. Two weeks following baseline assessment, students repeated the initial MCQ test and completed a postpodcast reaction survey. Data were analyzed using a paired t-test, multivariable regression analyses, and simple descriptive statistics. Fifty students were enrolled in the study. All participants undertook the baseline assessment. About 98% completed the postpodcast MCQ, while 94% completed the postpodcast reaction survey. All participants who undertook the reaction survey (n = 47) found the podcast helpful in explaining surgical concepts, 92% of participants found the podcast enjoyable to listen to. The most commonly reported activity undertaken while listening was "commuting/driving" (n = 24, 48%). The mean baseline MCQ score was 44.6%. The mean postpodcast MCQ score was 65.51%. There was a mean absolute increase in test score of 20.2% from baseline which was statistically significant (95%CI 14.67-25.6, p < 0.001). Implementation of this podcast series was associated with a statistically significant improvement in mean test score from baseline, reflecting knowledge acquisition. There was a positive user reaction and students were able to listen while performing other activities. Further evaluation of the educational outcomes associated with podcast use, particularly the effects on knowledge retention and clinical competence, is required.

Automated segmentation of the human supraclavicular fat depot via deep neural network in water-fat separated magnetic resonance images.

Human brown adipose tissue (BAT), mostly located in the cervical/supraclavicular region, is a promising target in obesity treatment. Magnetic resonance imaging (MRI) allows for mapping the fat content quantitatively. However, due to the complex heterogeneous distribution of BAT, it has been difficult to establish a standardized segmentation routine based on magnetic resonance (MR) images. Here, we suggest using a multi-modal deep neural network to detect the supraclavicular fat pocket. A total of 50 healthy subjects [median age/body mass index (BMI) =36 years/24.3 kg/m2] underwent MRI scans of the neck region on a 3 T Ingenia scanner (Philips Healthcare, Best, Netherlands). Manual segmentations following fixed rules for anatomical borders were used as ground truth labels. A deep learning-based method (termed as BAT-Net) was proposed for the segmentation of BAT on MRI scans. It jointly leveraged two-dimensional (2D) and three-dimensional (3D) convolutional neural network (CNN) architectures to efficiently encode the multi-modal and 3D context information from multi-modal MRI scans of the supraclavicular region. We compared the performance of BAT-Net to that of 2D U-Net and 3D U-Net. For 2D U-Net, we analyzed the performance difference of implementing 2D U-Net in three different planes, denoted as 2D U-Net (axial), 2D U-Net (coronal), and 2D U-Net (sagittal). The proposed model achieved an average dice similarity coefficient (DSC) of 0.878 with a standard deviation of 0.020. The volume segmented by the network was smaller compared to the ground truth labels by 9.20 mL on average with a mean absolute increase in proton density fat fraction (PDFF) inside the segmented regions of 1.19 percentage points. The BAT-Net outperformed all implemented 2D U-Nets and the 3D U-Nets with average DSC enhancement ranging from 0.016 to 0.023. The current work integrates a deep neural network-based segmentation into the automated segmentation of supraclavicular fat depot for quantitative evaluation of BAT. Experiments show that the presented multi-modal method benefits from leveraging both 2D and 3D CNN architecture and outperforms the independent use of 2D or 3D networks. Deep learning-based segmentation methods show potential towards a fully automated segmentation of the supraclavicular fat depot.

Sickness Absence and Disability Pension Among Patients With Chronic Pain in Interdisciplinary Treatment or Unspecified Interventions

Interdisciplinary treatment is a widely implemented strategy for the rehabilitation of patients with chronic pain. A primary treatment objective is to decrease the load on the social insurance system; however, it is questionable whether interdisciplinary treatment reduces sickness absence and disability pension (SA/DP). This register-based observational study compared SA and DP between patients in interdisciplinary treatment and unspecified interventions. With data from 7,752 Swedish specialist health care patients in their prime working age, we analyzed total net SA/DP days over 3 years from the first visit to a pain rehabilitation center. A zero-one-inflated beta model, adjusted for theoretically substantiated confounders, was used to estimate the mean differences in total days and the proportions of patients with both zero and maximum days. Compared with unspecified interventions, interdisciplinary treatment resulted in a mean (95% confidence interval) absolute increase of 50 (37, 62) total days, a 13.0% (11.3%, 14.6%) decrease in patients with zero days, and a 1.5% (.2%, 2.8%) decrease in patients with the maximum days. These findings support that interdisciplinary treatment increases SA/DP compared to less intensive interventions but reduces the risk of maximum days, implying that it is advantageous for patients with the highest absence. This highlights the need for improved patient selection procedures and the adaptation of interdisciplinary treatment programs to more adequately target SA/DP reduction. PerspectivesThis study provides an accessible overview of SA/DP among working-age patients with chronic pain in Swedish specialist health care. It also shows that interdisciplinary treatment does not decrease SA/DP more than alternative treatments in most patients but is advantageous for the patients with the longest absence.

Response rate in cardiac resynchronization therapy patients implanted with a left ventricular quadripolar lead and the MultiPoint™ pacing feature early activated. QUARTO III.

Although cardiac resynchronization therapy (CRT) is beneficial in most heart failure patients, up to 40% do not respond to CRT. It has been suggested that multipoint left ventricle pacing (MPP) would increase the response rate. To assess the CRT response rate at 6months in patients implanted with a CRT device with the MPP feature activated early after the implant. This was a multicentre, prospective, open-label and non-randomized study. The primary endpoint was response to biventricular pacing defined as >15% relative reduction in left ventricular end-systolic volume (LVESV) comparing echocardiography measurements performed at baseline and 6months by a core laboratory. Among secondary endpoints the combined endpoint of mortality or all-cause hospitalizations was evaluated. Primary study endpoint and clinical outcomes were compared to a Quarto II control cohort. Totally, 105 patients were included. The response rate was 64.6% (97.5% lower confidence bound 53%). Mean relative reduction in LVESV was 25.3%, and mean absolute increase in LVEF was 9.4%. The subjects with device programmed using anatomical approach showed a trend towards higher responder rate than those using the electrical approach (72% vs. 61.1%, p= 0.32). Finally, the combined incidence of mortality and or all-cause hospitalizations at 6month was 12.4%. Early activation of MPP was not associated to an advantage increasing echocardiography responders to CRT at 6months of follow-up. Nevertheless, patients programmed using widest pacing cathodes had a numerically higher responder rate. Finally, early activation of MPP was associated to a low incidence of clinical endpoints at 6months of follow-up.

Analysis of myocardial salvage with cardiac magnetic ressonance and angiography depending on the STEMI revascularization pathway in a PPCI centre

Abstract Background Reperfusion networks have permitted improvements in reperfusion delays in primary percutaneous coronary intervention (PPCI)-treated ST elevation myocardial infarction (STEMI). However, the impact on myocardial salvage (MS) of direct transfer to the catheterization laboratory (cath-lab) to minimize system delay remains unknown. Objective We sought to quantify the myocardial salvage index (MSI) acutely and to assess adverse remodeling at 6 months in PPCI-treated STEMI according to the mode of patient presentation. Methods Between 2005 and 2021 we included 493 patients in a single center registry of first PPCI-treated STEMI who were studied with Late gadolinium enhanced (LGE) cardiac magnetic resonance (CMR) in the acute phase. Among them, 414 (84.0%) underwent a second LGE-CMR at 6 months. Subjects were classified depending on the mode of presentation: those diagnosed out-of-hospital and directly transferred to the cath-lab by the Emergency Medical Services (EMS group, 29.82%); subjects with first medical contact in a PCI-capable hospital (PCI-H group, 41.75%); and patients presenting to a non-PCI-capable center and transferred for PCI (non-PCI-H group, 28.43%). We computed the angiographic area at risk by BARI score, and combined it with the LGE-CMR derived infarct size to compute a validated MSI, expressed as percentage of area at risk. The change in ejection fraction (EF) and indexed left ventricle end-diastolic volume (iLVEDV) from baseline to 6 months was also computed. Results The mean age was 58.9±11.9 years, 84.5% were male and 51.4% had anterior STEMI. Total median ischaemic time was (median (interquartile range)) 126 (105–161) min in the EMS group, 201 (145–321) min in the PCI-H group and 300 (173–592) min in the non-PCI-H group (p&amp;lt;0.01). MSI was 45.28±2.6%, 39.63±2.2% and 35.53±2.7% respectively (p=0.034). In a multiple linear regression model adjusting for relevant covariables, including initial TIMI flow, area at risk, Killip class, age, sex, diabetes, number of vessels and presence of collaterals, a 7.50% (95% CI 0.9 to 14.1%) increase in MSI was observed in the EMS group compared to the PCI-H group, and 11.03% (95% CI 3.9 to 18.2%) compared to the non-PCI-H group (p=0.027 and 0.003 respectively). At 6 months, the mean absolute increase in EF was 5.36±0.6% for the EMS group, 4.03±0.5% for the PCI-H group and 3.52±0.6% for the non-PCI-H group (p&amp;lt;0.05 in the adjusted analysis) and the increase in iLVEDV was 2.37±7.3, 5.51±6.6 and 18.30±7.6 mL/m2 respectively (p=0.28). Conclusions Patients with out-of-hospital diagnostis of STEMI by the EMS who were directly transferred to the cath-lab showed shorter total ischaemic times, resulting in increased myocardial salvage and a trend towards improved indexes of left ventricular function at 6 months. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Grant from La Maratό de TV3 and grant from Fundaciό La Caixa

Characterization of the deterioration of diabetes control in patients with a subsequent diagnosis of pancreatic cancer: A descriptive study

BackgroundDeterioration of diabetes control can be the first harbinger of pancreatic cancer. However, little is known about how to distinguish patients with pancreatic cancer-related diabetes deterioration from those with type 2 diabetes progression. We aimed to characterize the glycated hemoglobin (HbA1c) and body weight profile of pancreatic cancer patients with deteriorating diabetes before the cancer diagnosis. MethodsUsing data from the UK-based Clinical Practice Research Datalink (CPRD) GOLD, we established a study population including pancreatic cancer patients with diabetes deterioration in the >0.5–3 years before the cancer diagnosis and non-cancer patients with deterioration of type 2 diabetes (comparison group). Patients were considered to have diabetes deterioration if their glucose-lowering treatment was intensified. We characterized the longitudinal trajectories of HbA1c and body weight in pancreatic cancer patients compared with non-cancer patients before and after treatment intensification. ResultsThe mean absolute increase in HbA1c from the pre-deterioration period, i.e. the time >1–2 years before treatment intensification, to the time of treatment intensification, was 1.5% ± 1.6% in pancreatic cancer patients vs. 0.9% ± 1.4% in non-cancer patients. After treatment intensification, mean HbA1c remained elevated in pancreatic cancer patients, while it returned to the pre-deterioration level in non-cancer patients. Body weight decreased by 1.9% ± 6.4% in cancer patients and increased by 0.3% ± 5.2% in non-cancer patients between the pre-deterioration period and treatment intensification, on average. ConclusionsPancreatic cancer-related diabetes deterioration may frequently be characterized by pronounced increases in HbA1c, persistent elevation of HbA1c after treatment intensification, and concomitant weight loss.

Inhalable, Spray-Dried Terbinafine Microparticles for Management of Pulmonary Fungal Infections: Optimization of the Excipient Composition and Selection of an Inhalation Device.

Terbinafine is a broad-spectrum antifungal agent with therapeutic potential against pulmonary aspergillosis. The main aim of the current study was to investigate the potential of l-leucine, alone and in combination with mannitol, to improve the performance of spray-dried terbinafine microparticles for inhalation. The study also aimed to investigate the potential of the low resistance Cyclohaler® and the high resistance Handihaler® as inhalation devices for spray-dried microparticles. To this end, eight powder inhalation formulations of terbinafine were prepared by nano spray drying via a factorial experimental design. The formulations were evaluated in vitro for their potential to deliver the antifungal drug to the lungs using the Cyclohaler® and the Handihaler®. Leucine was superior as an excipient to mannitol and to mixtures of leucine and mannitol. Using leucine as an excipient resulted in formulations with fine particle fractions of up to 60.84 ± 0.67% w/w and particle mass median aerodynamic diameters of down to 1.90 ± 0.20 μm, whereas using mannitol as an excipient resulted in formulations with fine particle fractions of up to 18.75 ± 3.46% w/w and particle mass median aerodynamic diameters of down to 6.79 ± 0.82 μm. When leucine was used as an excipient, using 50% w/w rather than 25% w/w ethanol in water as a spray solvent enhanced the dispersibility of the particles, with a mean absolute increase in the formulation fine particle fraction of 9.57% w/w (95% confidence interval = 6.40–12.73% w/w). This was potentially underlain by enrichment of the particle surfaces with leucine. The Cyclohaler® outperformed the Handihaler® as an inhalation device for the developed formulations, with a mean absolute increase in the fine particle fraction of 9.17% w/w (95% confidence interval = 8.17–10.16% w/w).

Effectiveness and safety of elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis and advanced lung disease with the Phe508del/minimal function genotype

BackgroundElexacaftor/tezacaftor/ivacaftor (E/T/I) is a cystic fibrosis transmembrane conductance regulator (CFTR) triple combination therapy used for the treatment of cystic fibrosis (CF) in patients aged ≥12 years who have at least one copy of the Phe508del mutation (F) in the CFTR gene or another mutation that is responsive to treatment with E/T/I. This study determined the effectiveness and safety of E/T/I treatment in a cohort of CF patients. MethodsThis retrospective cohort study collected data from the first 6 months of treatment of patients with CF, compound heterozygotes for the F and a minimal function (MF) mutations, enrolled in an E/T/I compassionate use program only available to patients having ppFEV1<40 or who are considered for lung transplantation. Forty-seven patients were included. Follow-up was performed after 1, 3, and 6 months from the beginning of therapy, assessing lung function, body mass index (BMI), sweat chloride concentration (SCC), quality of life (QoL), and safety. ResultsAfter 6 months of treatment, the mean (standard deviation (SD)) SCC decreased from 91.1 (19.3) mmol/L to 46.2 (24.2) mmol/L. The decrease of SCC was accompanied by improvement of lung function (mean (95% Confidence Interval (CI) absolute increase in ppFEV1 was 10.69 (8.05,13.33) after 1 month and 14.16 (11.43, 16.89) after 6 months of treatment), nutrition (mean (SD) BMI increased from 20.7 (3.0) kg/m2 at baseline to 22.6 (3.1) after 6 months), and QoL. No safety concerns were observed. ConclusionsE/T/I was clinically effective and safe in patients with advanced CF lung disease with an F/MF genotype.

Targeting Hypertension Screening in Low- and Middle-Income Countries: A Cross-Sectional Analysis of 1.2Million Adults in 56 Countries.

BackgroundAs screening programs in low‐ and middle‐income countries (LMICs) often do not have the resources to screen the entire population, there is frequently a need to target such efforts to easily identifiable priority groups. This study aimed to determine (1) how hypertension prevalence in LMICs varies by age, sex, body mass index, and smoking status, and (2) the ability of different combinations of these variables to accurately predict hypertension.Methods and ResultsWe analyzed individual‐level, nationally representative data from 1 170 629 participants in 56 LMICs, of whom 220 636 (18.8%) had hypertension. Hypertension was defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or reporting to be taking blood pressure–lowering medication. The shape of the positive association of hypertension with age and body mass index varied across world regions. We used logistic regression and random forest models to compute the area under the receiver operating characteristic curve in each country for different combinations of age, body mass index, sex, and smoking status. The area under the receiver operating characteristic curve for the model with all 4 predictors ranged from 0.64 to 0.85 between countries, with a country‐level mean of 0.76 across LMICs globally. The mean absolute increase in the area under the receiver operating characteristic curve from the model including only age to the model including all 4 predictors was 0.05.ConclusionsAdding body mass index, sex, and smoking status to age led to only a minor increase in the ability to distinguish between adults with and without hypertension compared with using age alone. Hypertension screening programs in LMICs could use age as the primary variable to target their efforts.

Sample pooling is a viable strategy for SARS-CoV-2 detection in low-prevalence settings

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has significantly increased demand on laboratory throughput and reagents for nucleic acid extraction and polymerase chain reaction (PCR). Reagent shortages may limit the expansion of testing required to scale back containment measures. The aims of this study were to investigate the viability of sample pooling as a strategy for increasing test throughput and conserving PCR reagents; and to report our early experience with pooling of clinical samples.A pre-implementation study was performed to assess the sensitivity and theoretical efficiency of two, four, and eight-sample pools in a real-time reverse transcription PCR-based workflow. A standard operating procedure was developed and implemented in two laboratories during periods of peak demand, inclusive of over 29,000 clinical samples processed in our laboratory.Sensitivity decreased (mean absolute increase in cycle threshold value of 0.6, 2.3, and 3.0 for pools of two, four, and eight samples, respectively) and efficiency increased as pool size increased. Gains from pooling diminished at high disease prevalence. Our standard operating procedure was successfully implemented across two laboratories. Increased workflow complexity imparts a higher risk of errors, and requires risk mitigation strategies. Turnaround time for individual samples increased, hence urgent samples should not be pooled.Pooling is a viable strategy for high-throughput testing of SARS-CoV-2 in low-prevalence settings.

The evaluation of a slim perimodiolar electrode: surgical technique in relation to intracochlear position and cochlear implant outcomes

PurposeIn cochlear implantation (CI), the two factors that are determined by the surgeon with a potential significant impact on the position of the electrode within the cochlea and the potential outcome, are the surgical technique and electrode type. The objective of this prospective study was to evaluate the position of the slim, perimodiolar electrode (SPE), and to study the influence of the SPE position on CI outcome.MethodsTwenty-three consecutively implanted, adult SPE candidates were included in this prospective cohort study conducted between December 2016 and April 2019. Mean age at surgery was 59.5 years. Mean preoperative residual hearing was 92.2 dB. Intra-operative fluoroscopy and high-resolution computed tomography scans were performed to evaluate electrode position after insertion using a cochleostomy (CS) approach. Follow-up was 12 months after implantation; residual hearing (6–8 weeks) and speech perception (6–8 weeks and 12 months) were evaluated in relation to the intracochlear SPE position.ResultsIn most patients in whom the SPE was positioned in the scala tympani residual hearing was preserved [mean absolute increase in PTA of 4.4 dB and 77.2% relative hearing preservation (RHP%)]. Translocation into the scala vestibuli occurred in 36% of the insertions, resulting in a mean absolute increase in PTA of 17.9 dB, and a RHP% of 19.2%. Participants with a translocation had poorer speech perception scores at 12-month follow-up.ConclusionGiven the incidence of CS-associated translocations with the SPE and the negative effect on outcome, it is advised to insert the SPE using the (extended) round window approach.

1715. A Randomized, Double-Blind, Placebo-Controlled Multicenter Phase 2 Trial to Examine the Effects of DAS181 in Immunocompromised (IC) Patients With Parainfluenza Virus (PIV) Lower Respiratory Tract Infection (LRTI) on Supplemental Oxygen (SO)

BackgroundPIV infections are an important cause of morbidity and mortality in IC patients. DAS181, a sialidase fusion protein, has demonstrated activity in preclinical and clinical studies.MethodsAdult IC patients diagnosed with PIV LRTI on chest imaging and required SO ≥ 2 L/minute were randomized 2:1 (stratified by mechanical ventilation [MV] at baseline) to nebulized DAS181 (4.5 mg in 3.5 mL/day) or matching placebo for up to 10 days. The primary endpoint was the proportion of patients reaching clinical stability survival (CSS, defined as alive, resolution of SO requirement, and normalization of vital signs) by Day 45.ResultsFrom 2014 to 2016, 110 patients were randomized and received study drug (74 DAS181 and 36 placebo). Median age was 57 years (range, 18–85). The majority were hematopoietic cell transplant (HCT) recipients (74), followed by hematological malignancy/solid tumor patients on chemotherapy (29), and lung transplant recipients (7). Day 45 CSS was achieved by 39.2% of DAS181-treated patients compared with 31.4% of placebo (P = 0.29), while the proportion among non-MV patients was 45.0% vs. 31.0% (difference −14.0%, P = 0.15), respectively. Time to CSS in the non-MV stratum was shorter in DAS181-treated patients (figure). Median change in nasopharyngeal PIV viral load by Day 10 and median hospitalization days were −1.44 vs. −0.68 log10 (P = 0.51) and 13.5 vs. 21 days (P = 0.10) for DAS181 and placebo, respectively. Mean absolute increase from baseline FEV1% predicted was 16.82 for DAS181 vs. 2.02 for placebo (P = 0.001). Post-hoc analysis on the probability to return to room air (RTRA) suggested that DAS181 reduced SO need in the non-MV stratum after Day 21 (P = 0.09). HCT recipients within 360 days from transplant had a 40.8% treatment effect on RTRA at Day 28 (P = 0.04) and 36.7% on mortality at Day 45 when compared with placebo (P = 0.06). The rate of adverse events was similar in both treatment groups. Day 45 all-cause mortality was comparable in both groups (32.4% DAS181 vs. 31.4% placebo).ConclusionDAS181 was well tolerated and showed a signal for clinical efficacy in IC patients with PIV LRTI. DAS181 was granted Breakthrough Therapy Designation for the treatment of PIV LRTI in IC patients and a phase 3 trial is being planned. Disclosures R. F. Chemaly, Ansun Biopharma: Consultant and Investigator, Consulting fee and Research grant. R. Moss, Ansun Biopharma: Employee, Salary. F. M. Marty, Ansun Biopharma: Investigator, Research grant. C. R. Wolfe, Ansun Biopharma: Investigator, Research grant. S. J. Lawrence, Ansun Biopharma: Investigator, Research grant. S. Dadwal, Ansun Biopharma: Investigator, Research grant. R. Soave, Ansun Biopharma: Investigator, Research grant. J. Hwang, Ansun Biopharma: Employee, Salary. S. Hawley, Ansun Biopharma: Employee, Salary. R. Routh, Ansun Biopharma: Employee, Salary. J. Ho, Ansun Biopharma: Employee, Salary. G. Wang, Ansun Biopharma: Employee, Salary. N. Chang, Ansun Biopharma: Employee, Salary. M. Boeckh, Ansun Biopharma: Consultant and Investigator, Consulting fee and Research support.

Serial Fractional Flow Reserve Measurements Post Coronary Chronic Total Occlusion Percutaneous Coronary Intervention.

Background The aim of this study was to evaluate the functional result of chronic total occlusion percutaneous coronary intervention (PCI) measured by fractional flow reserve (FFR) immediately post the index procedure and at short-term follow-up. Methods and Results This was a prospective single-center observational study. Consecutive patients with right coronary artery chronic total occlusion scheduled for elective PCI were included. FFR measurements were performed immediately after successful PCI and at 4 months follow-up. Twenty-six patients completed baseline and follow-up measurements. Mean age was 61.2±9.7 years, 88.5% of the patients were male, and 19.2% were diabetic. The mean FFR immediately after successful chronic total occlusion PCI was 0.82±0.10 and significantly increased to 0.89±0.07 at 4 months ( P<0.001). The FFR increased in 77% of the patients with a mean absolute increase of 0.07±0.08. The incidence of FFR ≤0.80 immediately after PCI was significantly higher amongst patients with subintimal versus intraplaque recanalization (23% versus 12%; P=0.03). At 4 months, FFR ≤0.80 was found only in 2 patients with subintimal recanalization. At follow-up, 42.7% of the patients continued to have an FFR <0.90. Conclusions Post chronic total occlusion PCI, FFR increased significantly at short-term follow-up compared with measurements post index procedure. Because FFR remained <0.90 in many cases, further efforts should be made to optimize procedural results.

Effectiveness of ivacaftor in cystic fibrosis patients with non-G551D gating mutations

BackgroundThe cystic fibrosis transmembrane conductance regulator (CFTR) potentiator ivacaftor is approved for patients with CF with gating and residual function CFTR mutations. We report the results of an observational study investigating its effects in CF patients with non-G551D gating mutations. MethodsPatients with non-G551D gating mutations were recruited to an open-label study evaluating ivacaftor. Primary outcomes included: lung function, sweat chloride, weight gain, and quality of life scores. ResultsTwenty-one subjects were enrolled and completed 6 months follow-up on ivacaftor; mean age was 25.6 years with 52% <18. Baseline ppFEV1 was 68% and mean sweat chloride 89.6 mEq/L. Participants experienced significant improvements in ppFEV1 (mean absolute increase of 10.9% 95% CI = [2.6,19.3], p = 0.0134), sweat chloride (−48.6 95% CI = [−67.4,-29.9], p < 0.0001), and weight (5.1 kg, 95% CI = [2.8, 7.3], p = 0.0002). ConclusionsPatients with non-G551D gating mutations experienced improved lung function, nutritional status, and quality of life. This study supports ongoing use of ivacaftor for patients with these mutations.

Nonrigid active shape model-based registration framework for motion correction of cardiac T1 mapping.

Accurate reconstruction of myocardial T1 maps from a series of T1 -weighted images consists of cardiac motions induced from breathing and diaphragmatic drifts. We propose and evaluate a new framework based on active shape models to correct for motion in myocardial T1 maps. Multiple appearance models were built at different inversion time intervals to model the blood-myocardium contrast and brightness changes during the longitudinal relaxation. Myocardial inner and outer borders were automatically segmented using the built models, and the extracted contours were used to register the T1 -weighted images. Data acquired from 210 patients using a free-breathing acquisition protocol were used to train and evaluate the proposed framework. Two independent readers evaluated the quality of the T1 maps before and after correction using a four-point score. The mean absolute distance and Dice index were used to validate the registration process. The testing data set from 180 patients at 5 short axial slices showed a significant decrease of mean absolute distance (from 3.3 ± 1.6 to 2.3 ± 0.8 mm, P < 0.001) and increase of Dice (from 0.89 ± 0.08 to 0.94 ± 0.4%, P < 0.001) before and after correction, respectively. The T1 map quality improved in 70 ± 0.3% of the motion-affected maps after correction. Motion-corrupted segments of the myocardium reduced from 21.8 to 8.5% (P < 0.001) after correction. The proposed method for nonrigid registration of T1 -weighted images allows T1 measurements in more myocardial segments by reducing motion-induced T1 estimation errors in myocardial segments. Magn Reson Med 80:780-791, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

STACK NUMBER INFLUENCE ON THE ACCURACY OF ASTER GDEM (V2)

Abstract. In this research, the influence of stack number (STKN) on the accuracy of Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) Global DEM (GDEM) has been investigated. For this purpose, two data sets of ASTER and Reference DEMs from two study areas with various topography (Bomehen and Tazehabad) were used. The Results show that in both study areas, STKN of 19 results in minimum error so that this minimum error has small difference with other STKN. The analysis of slope, STKN, and error values shows that there is no strong correlation between these parameters in both study areas. For example, the value of mean absolute error increase by changing the topography and the increase of slope values and height on cells but, the changes in STKN has no important effect on error values. Furthermore, according to high values of STKN, effect of slope on elevation accuracy has practically decreased. Also, there is no great correlation between the residual and STKN in ASTER GDEM.

Phase III randomized trial comparing intravenous to oral iron in patients with cancer‐related iron deficiency anemia not on erythropoiesis stimulating agents

We aimed to find the optimal route of iron supplementation in patients with malignancy and iron deficiency (true or functional) anemia not receiving erythropoiesis stimulating agents (ESA). Adult patients with malignancy requiring chemotherapy, hemoglobin (Hb) <12 g/dL and serum ferritin <100 mcg/mL, transferrin saturation <20% or hypochromic red blood cells >10% were randomized to intravenous (IV) iron sucrose or oral ferrous sulfate. The primary endpoint was change in Hb from baseline to 6 weeks. Secondary endpoints included blood transfusion, quality of life (QoL), toxicity, response and overall survival. A total of 192 patients were enrolled over 5 years: 98 on IV arm and 94 on oral arm. Median age was 51 years; over 95% patients had solid tumors. The mean absolute increase in Hb at 6 weeks was 0.11 g/dL (standard deviation [SD]: 1.48) in IV arm and -0.16 g/dL (SD: 1.36) in oral arm, P = 0.23. Twenty-three percent patients on IV iron and 18% patients on oral iron had a rise in Hb of ≥1 g/dL at 6 weeks, P = 0.45. Thirteen patients (13.3%) on the IV iron arm and 14 patients (14.9%) on the oral arm required blood transfusion, P = 1.0. Gastrointestinal toxicity (any grade) developed in 41% patients on IV iron and 44% patients on oral iron, P = 1.0. 5 patients on IV iron and none on oral iron had hypersensitivity, P = 0.06. QoL was not significantly different between the two arms. IV iron was not superior to oral iron in patients with malignancy on chemotherapy and iron deficiency anemia.

Overdiagnosis and overtreatment of thyroid cancer: A population-based temporal trend study.

BackgroundThe increase in incidence of thyroid cancer during the last decades without concomitant rise in mortality may reflect the growing detection of indolent forms of thyroid cancer, and may have fueled unnecessary thyroidectomies. Our aim was therefore, to compare recent secular trends in surgical intervention rate for thyroid cancer with the incidence and mortality of thyroid cancer to assess overdiagnosis and resulting overtreatment.MethodsWe conducted a population-based temporal trend study in Switzerland from 1998 to 2012. All cases of invasive thyroid cancer, deaths from thyroid cancer, and cancer-related thyroidectomies were analyzed. We calculated changes in age-standardized thyroid cancer incidence rates, stratified by histologic subtype and tumor stage, thyroid cancer-specific mortality, and thyroidectomy rates.ResultsBetween 1998 and 2012, the age-standardized annual incidence of thyroid cancer increased from 5.9 to 11.7 cases/100,000 among women (annual mean absolute increase: +0.43/100,000/year) and from 2.7 to 3.9 cases/100,000 among men (+0.11/100,000/year). The increase was limited to the papillary subtype, the most indolent form of thyroid cancer. The incidence of early stages increased sharply, the incidence of advanced stages increased marginally, and the mortality from thyroid cancer decreased slightly. There was a three- to four-fold increase in the age-standardized annual thyroidectomy rate in both sexes.ConclusionsWe observed a large increase in the incidence of thyroid cancer, limited to papillary and early stage tumors, with a three- to four-fold parallel increase in thyroidectomy. The mortality slightly decreased. These findings suggest that a substantial and growing part of the detected thyroid cancers are overdiagnosed and overtreated.ImpactTargeted screening and diagnostic strategies are warranted to avoid overdetection and unnecessary treatment of thyroid cancers.

Standardized Treatment of Pulmonary Exacerbations (STOP) study: Physician treatment practices and outcomes for individuals with cystic fibrosis with pulmonary Exacerbations

BackgroundPulmonary Exacerbations (PEx) are associated with increased morbidity and mortality in individuals with CF. PEx management practices vary widely, and optimization through interventional trials could potentially improve outcomes. The object of this analysis was to evaluate current physician treatment practices and patient outcomes for PEx. MethodsThe Standardized Treatment of Pulmonary Exacerbations (STOP) observational study enrolled 220 participants ≥12years old admitted to the hospital for PEx at 11 U.S. CF centers. Spirometry and daily symptom scores were collected during the study. Physicians were surveyed on treatment goals and their management practices were observed. Treatment outcomes were compared to stated goals. ResultsThe mean (SD) duration of IV antibiotic treatment was 15.9 (6.0) days. Those individuals with more severe lung disease (<50% FEV1) were treated nearly two days longer than those with >50% FEV1. Physician-reported FEV1 improvement goals were 10% (95% CI: 5%, 14%) lower for patients with 6-month baseline FEV1 ≤50% predicted compared with those with 6-month baseline FEV1 >50% predicted. There were clinically and statistically significant improvements in symptoms from the start of IV antibiotic treatment to the end of IV antibiotic treatment and 28days after the start of treatment. The mean absolute increase in FEV1 from admission was 9% predicted at end of IV antibiotic treatment, and 7% predicted at day 28. Only 39% fully recovered lost lung function, and only 65% recovered at least 90% of lost lung function. Treatment was deemed successful by 84% of clinicians, although 6-month baseline FEV1 was only recovered in 39% of PEx. ConclusionsIn this prospective observational study of PEx, treatment regimens and durations showed substantial variation. A significant proportion of patients did not reach physician's treatment goals, yet treatment was deemed successful.