Acute Type B Intramural Hematoma: Novel Insights in the Endovascular Era.

BACKGROUND: The pathophysiology and behavior of acute type B intramural hematoma (TBIMH) is poorly understood. The purpose of this study is to characterize the pathophysiology, fate, and outcomes of TBIMH in the endovascular era. METHODS: A retrospective analysis of a US Aortic Database identified 70 patients with TBIMH from 2008 to 2022. Patients were divided into groups and analyzed based upon subsequent management: early thoracic endovascular aortic repair (TEVAR; Group 1) or hospital discharge on optimal medical therapy (OMT) (Group 2). RESULTS: Of 70 total patients, 43% (30/70) underwent TEVAR (Group 1) and 57% (40/70) were discharged on OMT (Group 2). There were no significant differences in age, demographics, or comorbidities between groups. Indications for TEVAR in Group 1 were as follows: 1) Penetrating atheroscletoic ulcer (PAU) or ulcer-like projection (n = 26); 2) Descending thoracic aortic aneurysm (n = 3); or 3) Progression to type B aortic dissection (TBAD) (n = 2). Operative mortality was zero. No patient suffered a stroke or spinal cord ischemia. During the follow-up period, 50% (20/40) of Group 2 patients required delayed surgical intervention, including TEVAR in 14 patients and open repair in 6 patients. Indications for surgical intervention were as follows: 1) Development of a PAU / ulcer-like projection (n = 13); 2) Progression to TBAD (n = 3), or 3) Concomitant aneurysmal disease (n = 4). Twenty patients did not require surgical intervention. Of the initial cohort, 71% of patients required surgery, 9% progressed to TBAD, and 19% had regression or stability of TBIMH with OMT alone. CONCLUSIONS: The most common etiology of TBIMH is an intimal defect. Progression to TBAD and intramural hematoma regression without an intimal defect occurs in a small percentage of patients. An aggressive strategy with endovascular therapy and close surveillance for TBIMH results in excellent short-term and long-term outcomes.

Bicuspid aortic valve sparing root replacement.

BACKGROUND AND AIM OF STUDY: Mid and long-term data regarding the durability of bicuspid aortic valve sparing root replacement is not completely understood. In this study, our institutional experience is reviewed regarding this procedure with special attention to the operative technique. METHODS: From 2004 to 2019, 1241 patients underwent aortic root replacement and of these 79 patients underwent bicuspid aortic valve sparing root replacement. Early and late outcomes along with echocardiographic data were reviewed. Univariate analysis was used to identify risk factors for mortality. RESULTS: Median age at operation was 43 (inner quartile range: 34.5-50.5) years, with 17% (14) being female. Median follow up time was 4 (inner quartile range: 1-8) years with 359 years of total follow up. Early mortality was 2.5% (2). Overall 10-year freedom from aortic valve intervention was 95.6%. Risk factor analysis did not demonstrate preoperative root diameter, aortic diameter, or aortic insufficiency to be risk factors for mortality. CONCLUSION: Bicuspid aortic valve sparing root replacement can be performed safely in the setting of aortic root pathology and valve insufficiency. With appropriate selection and excellent surgical technique, long-term durable valve function is observed without the need for repeat valve intervention.

Effects and outcomes of cardiac surgery in patients with cardiometabolic syndrome.

INTRODUCTION: Cardiometabolic syndrome (CMS) is diabetes mellitus (or insulin resistance) plus any two of the following risk factors: hypertension, obesity, and hyperlipidemia. The correlation of metabolic syndrome with cardiovascular disease and the increase in the prevalence of patients with risk factors have solidified the importance of continued focus on metabolic syndrome. We retrospectively evaluated single-center data to determine if there is an association between CMS and outcomes. METHODS: The local Society of Thoracic Surgeons Adult Cardiac Database was queried for consecutive coronary bypass (CABG) cases from 2002 to 2010. Short and long-term outcomes were compared between groups of patients with CMS and then risk-adjusted using multiple regression models with adjusted odds ratios and hazard ratios. RESULTS: Of 11 021 CABG cases, 3881 (35.2%) had CMS, with an annual prevalence that increased from 32% to 40% during the study. Patients with CMS were more likely to have prior cerebrovascular diseases, strokes, renal insufficiency, and worse New York Heart Association status. Unadjusted postoperative comparisons revealed that patients with CMS had higher rates of stroke, renal failure, dialysis, deep sternal wound infection, and longer intensive care unit and hospital length of stay. Risk-adjusted odds ratios did not reveal a significant impact on short-term outcomes, however, adjusted hazard ratios continued to demonstrate significant decreases in long-term survival in patients with CMS. CONCLUSIONS: Patients with CMS were more likely to present with increased comorbidities. Patients with CMS undergoing CABG were at risk for worse short-term secondary postoperative outcomes and reduced long-term survival. The data supports the need for further investigation for risk reduction surrounding operative revascularization.

Timing of Recognition for Perioperative Strokes Following Cardiac Surgery.

INTRODUCTION: More than half of reported perioperative strokes following cardiac surgery are identified beyond postoperative day one. The objective of our study was to determine preoperative and intraoperative factors that are associated with stroke following cardiac surgery and to identify factors that may contribute delayed recognition of perioperative stroke. METHODS: Patients undergoing coronary artery bypass surgery or isolated valve surgery from January 2, 2015 to April 28, 2017 at an academic health system were identified from the Society of Thoracic Surgeons Registry. We determined preoperative and intraoperative factors associated with perioperative stroke. Two neurologists performed retrospective chart reviews on perioperative stroke patients to determine the last seen well time and the stroke cause. RESULTS: During the study period, 2795 patients underwent coronary artery bypass surgery or isolated valve surgery (mean age 64 ± 11 years, 71% male, 72% Caucasian, 9% history of stroke), of which 43 (1.5%) had a perioperative stroke; 31 (72%) patients had an embolic mechanism of stroke based on neuroimaging. In multivariable analysis, perioperative strokes were independently associated with increasing age (OR 1.04, 95% 1.01-1.07), history of stroke (OR 2.73, 95% CI 1.47-5.06), and history of thoracic aorta disease (OR 3.36, 95% CI 1.16-9.71). Strokes were identified after postoperative day one in 32 (74%) patients of which 26 (81%) had a preoperative last seen well time. CONCLUSION: Given the high frequency of preoperative last seen well time in perioperative stroke patients who are identified after postoperative day one, delayed stroke recognition may contribute to the bimodal distribution in timing of perioperative stroke. Frequent neurological monitoring within 24 hours after CABG or isolated valve surgery should be considered for all patients undergoing cardiac surgery, particularly elderly patients and those with a history of stroke or thoracic aorta disease, to improve early stroke recognition.

The distance of the primary intimal tear from the left subclavian artery predicts aortic growth in uncomplicated type B aortic dissection.

OBJECTIVE: Controversy exists about the optimal treatment of acute uncomplicated type B aortic dissection (auTBAD). Optimal medical therapy (OMT) provides excellent short-term outcomes, but long-term results are poor. Ideally, auTBAD patients who will fail to respond to OMT in the chronic phase could be identified and undergo thoracic endovascular aortic repair. The purpose of this study was to identify radiographic predictors of auTBAD patients who will fail to respond to OMT. METHODS: A review of the Emory aortic database from 2000 to 2017 identified 320 auTBAD patients initially treated with OMT. From this cohort, 121 patients with two or more contrast-enhanced imaging scans were available for analysis. These patients were initially divided into groups based on growth of the thoracic aorta ≥10 mm or intervention due to aneurysmal growth: growth (n = 72) and no growth (n = 49). TeraRecon (Foster City, Calif) imaging software was used to analyze characteristics of the primary intimal tear (PIT), false lumen, and overall aortic size. Finally, Cox proportional hazards models were constructed to estimate hazard ratios and to identify predictors of OMT failure. RESULTS: The mean age of all patients was 54 ± 11 years, and 67% were male. Thirty-eight patients (53%) in the growth group underwent intervention. There were no differences between groups in age, hypertension, diabetes mellitus, tobacco abuse, or chronic obstructive pulmonary disease. The distance of the PIT from the left subclavian artery in patients with auTBAD was significantly shorter in the growth group (growth, 27 mm [9-66 mm]; no growth, 77 mm [26-142 mm]; P < .01). Multivariable Cox regression analysis identified the distance of the PIT from the left subclavian artery and a thoracic aortic diameter >45 mm as independent predictors of failure of OMT. Partial false lumen thrombosis was not a predictor of aortic growth. CONCLUSIONS: The distance of the PIT from the left subclavian artery is a predictor of aortic growth in auTBAD. Patients with a primary tear located in zone 3 of the proximal descending thoracic aorta should be monitored closely and may be considered for early thoracic endovascular aortic repair in the setting of auTBAD.

Effect of Parity on Pregnancy-Associated Hypertension Among Asian American Women in the United States.

OBJECTIVES: Pregnancy-associated hypertension (PAH) includes gestational hypertension, preeclampsia and eclampsia. Although a protective effect of multi-parity on PAH has been reported in previous studies, the association has not been examined among Asian American women in the U.S. METHODS: Using data from 2014 U.S. National Vital Statistics System, we examined the prevalence of PAH among Asian American women who had singleton live births (N = 235,303), and its association with parity (number of previous pregnancies including live births and fetal deaths) controlling for potential confounders. We estimated adjusted odds ratios (aORs) and 95% confidence intervals (CI) using multivariable logistic regression analysis. RESULTS: Overall, 2.72% (95% CI 2.66%, 2.79%) of Asian American women were recorded to have PAH during pregnancy. Parity was inversely associated with PAH in our study, where Asian American women who had 1-2 and 3 or more previous pregnancies had significantly lower odds of PAH (aOR 0.61, 95% CI 0.58, 0.65; and aOR 0.62, 95% CI 0.57, 0.68, respectively) compared to nulliparous women, after controlling for potential confounders. CONCLUSIONS: Recent U.S. vital statistics data revealed that nulliparity is significantly associated with PAH among Asian American women. Future studies should identify specific factors that are associated with PAH and factors contributing to disparities in PAH risk among Asian American women.

Anatomical risk models for paravalvular leak and landing zone complications for balloon-expandable transcatheter aortic valve replacement.

BACKGROUND: Though several anatomical characteristics have been reported separately as risk factors for paravalvular leak (PVL) and landing zone (LZ) complications after transcatheter aortic valve replacement (TAVR), multivariate risk models are needed. METHODS: Patients that underwent balloon-expandable TAVR with multidetector cardiac computed tomography (MDCT) sizing were studied. MDCT images were analyzed and the association between anatomical factors and ≥mild PVL, ≥moderate PVL, and LZ complications (annular rupture, requirement of new permanent pacemaker, and coronary obstruction) was determined, and subsequently competing predictive models were developed and validated. RESULTS: A total of 316 consecutive TAVR patients were included. Median age was 82.0 years (74.0-87.0) and STS score was 8.3% (5.4-10.9). Factors associated with ≥mild PVL included TAVR with Sapien/Sapien XT vs. Sapien 3 (OR = 2.50, 95% CI = 1.24-5.07), LVOT nontubularity (OR = 1.02, 95% CI = 1.01-1.04), LZ calcification (OR = 1.01, 95% CI = 1.00-1.01), and low cover index (OR = 0.94, 95% CI = 0.91-0.96). Factors associated with LZ complications included LZ calcification (OR = 1.01, 95% CI 1.00-1.01), leaflet asymmetry (OR = 1.01, 95% CI 1.01-1.02), and cover index (OR = 1.09, 95% CI 1.03-1.14). Predictive models for ≥mild PVL (AUC = 0.71, 95% CI = 0.66-0.77), ≥moderate PVL (AUC = 0.75, 95% CI = 0.65-0.84), and LZ complications (AUC = 0.77, 95% CI = 0.67-0.87) were created using procedural details and anatomical data from the MDCT. Clinical variables were not included as they were poorly correlated with the occurrence of PVL and LZ complications. For each outcome, the area under the curve (AUC) of the multivariate model was superior to the model consisting only of individual factors. CONCLUSIONS: A model using procedural/anatomical characteristics derived from MDCT predicts ≥mild PVL, ≥moderate PVL, and LZ complications post-TAVR. Incorporation of anatomical risks into clinical practice may help stratify patients before TAVR. © 2017 Wiley Periodicals, Inc.

Effect of Angiotensin II Type I Receptor Blockade with Valsartan on Carotid Artery Atherosclerosis: A Double Blind Randomized Clinical Trial Comparing Valsartan and Placebo (EFFERVESCENT).

BACKGROUND: Progression of atherosclerosis is associated with a greater risk for adverse outcomes. Angiotensin II plays a key role in the pathogenesis and progression of atherosclerosis. We aimed to investigate the effects of angiotensin II type-1 receptor blockade with Valsartan on carotid wall atherosclerosis, with the hypothesis that Valsartan will reduce progression of atherosclerosis. METHODS: Subjects (n = 120) with carotid intima-media thickness >0.65 mm by ultrasound were randomized (2:1) in a double-blind manner to receive either Valsartan or placebo for 2 years. Bilateral T2-weighted black-blood carotid magnetic resonance imaging was performed at baseline, 12 and 24 months. Changes in the carotid bulb vessel wall area and wall thickness were primary endpoints. Secondary endpoints included changes in carotid plaque thickness, plasma levels of aminothiols, C-reactive protein, fibrinogen, and endothelium-dependent and -independent vascular function. RESULTS: Over 2 years, the carotid bulb vessel wall area decreased with Valsartan (-6.7, 95% CI [-11.6, -1.9] mm(2)) but not with placebo (3.4, 95% CI [-2.8, 9.6] mm(2)), P = .01 between groups. Similarly, mean wall thickness decreased with Valsartan (-0.18, 95% CI [-0.30, -0.06] mm), but not with placebo (0.08, 95% CI [-0.07, 0.23] mm), P = .009 between groups. Furthermore, plaque thickness decreased with Valsartan (-0.35, 95% CI [-0.63, -0.08] mm) but was unchanged with placebo (+0.28, 95% CI [-0.11, 0.69] mm), P = .01 between groups. These findings were unaffected by statin therapy or changes in blood pressure. Notably, there were significant improvements in the aminothiol cysteineglutathione disulfide, and trends to improvements in fibrinogen levels and endothelium-independent vascular function. CONCLUSIONS: In subjects with carotid wall thickening, angiotensin II type-1 receptor blockade was associated with regression in carotid atherosclerosis. Whether these effects translate into improved outcomes in subjects with subclinical atherosclerosis warrants investigation.

Maternal Chlamydia Infection During Pregnancy and Risk of Cyanotic Congenital Heart Defects in the Offspring.

OBJECTIVES: Genital Chlamydia is a common bacterial sexually-transmitted infection among reproductive aged women, particularly younger populations. Cyanotic congenital heart defects (CCHDs) constitute about one quarter of all cardiac malformations at birth, and are associated with high rate of morbidity and mortality. Epidemiological research on the association between maternal Chlamydia during pregnancy and CCHDs in the offspring is lacking. METHODS: Using data from the 2012 United States birth certificates, we examined the association between CCHDs and prenatal exposure to Chlamydia among live singleton births with CCHDs (n = 2487) and unaffected singleton births (n = 3,334,424). We estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis for all CCHDs combined, and isolated CCHDs (without other major congenital malformations). RESULTS: Overall 1.7% of case and 1.7% of control women reported having Chlamydia during their pregnancies. After controlling for potential confounders, we found a weak positive association between maternal Chlamydia during pregnancy and all CCHDs combined (aOR = 1.39; 95% CI 1.02-1.90). The positive association persisted for isolated CCHD cases, but with marginal significance (aOR = 1.34; 95% CI 0.96-1.74). Subgroup analyses for younger women showed an increased risk for CCHDs; however, the associations were not statistically significant. CONCLUSIONS: Maternal exposure to Chlamydia during pregnancy was weakly associated with a higher risk of CCHDs in the offspring. The finding should be interpreted with caution due to limitations of birth certificate data. Future studies using more robust data sources are warranted to further study the association between maternal Chlamydia during pregnancy and CCHDs in the offspring.

Vitamin D status is independently associated with plasma glutathione and cysteine thiol/disulphide redox status in adults.

OBJECTIVE: Redox status and inflammation are important in the pathophysiology of numerous chronic diseases. Epidemiological studies have linked vitamin D status to a number of chronic diseases. We aimed to examine the relationships between serum 25-hydroxyvitamin D [25(OH)D] and circulating thiol/disulphide redox status and biomarkers of inflammation. DESIGN: This was a cross-sectional study of N = 693 adults (449 females, 244 males) in an apparently healthy, working cohort in Atlanta, GA. Plasma glutathione (GSH), cysteine (Cys) and their associated disulphides were determined with high-performance liquid chromatography, and their redox potentials (Eh GSSG and Eh CySS) were calculated using the Nernst equation. Serum inflammatory markers included interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-α, assayed on a multiplex platform, and C-reactive protein (CRP), assayed commercially. Relationships were assessed with multiple linear regression analyses. RESULTS: Serum 25(OH)D was positively associated with plasma GSH (ß ± SE: 0·002 ± 0·0004) and negatively associated with plasma Eh GSSG (ß ± SE: -0·06 ± 0·01) and Cys (ß ± SE: -0·01 ± 0·003) (P < 0·001 for all); statistical significance remained after adjusting for age, gender, race, percentage body fat and traditional cardiovascular risk factors (P = 0·01-0·02). The inverse relationship between serum 25(OH)D and CRP was confounded by percentage body fat, and full adjustment for covariates attenuated serum 25(OH)D relationships with other inflammatory markers to nonstatistical significance. CONCLUSIONS: Serum 25(OH)D concentrations were independently associated with major plasma thiol/disulphide redox systems, suggesting that vitamin D status may be involved in redox-mediated pathophysiology.

Effects of clopidogrel therapy on oxidative stress, inflammation, vascular function, and progenitor cells in stable coronary artery disease.

BACKGROUND: Traditional cardiovascular risk factors lead to endothelial injury and activation of leukocytes and platelets that initiate and propagate atherosclerosis. We proposed that clopidogrel therapy in patients with stable coronary artery disease imparts a pleiotropic effect that extends beyond antiplatelet aggregation to other atheroprotective processes. METHODS: Forty-one subjects were randomized in a double-blind, placebo-controlled, crossover study to receive either clopidogrel 75 mg daily or placebo for 6 weeks and then transitioned immediately to the other treatment for an additional 6 weeks. We assessed (1) endothelial function as flow-mediated dilation of the brachial artery, (2) arterial stiffness and central augmentation index using applanation tonometry, (3) vascular function as fingertip reactive hyperemia index, (4) inflammation by measuring plasma CD40 ligand and serum high-sensitivity c-reactive protein levels, (5) oxidative stress by measuring plasma aminothiols, and (6) circulating progenitor cells, at baseline and at the end of each 6-week treatment period. RESULTS: Clopidogrel therapy resulted in a significant reduction in soluble CD40 ligand (P = 0.03), a prothrombotic and proinflammatory molecule derived mainly from activated platelets. However, clopidogrel therapy had no effect on endothelial function, arterial stiffness, inflammatory and oxidative stress markers, or progenitor cells. CONCLUSIONS: Our findings suggest a solitary antiplatelet effect of clopidogrel therapy in patients with stable coronary artery disease, with no effect on other subclinical markers of cardiovascular disease risk.

Distribution of Candida species isolated from blood cultures in hospitals in Osaka, Japan.

BACKGROUND: Candida species are clinically important causes of bloodstream infections because their mortality is very high. Given that some species of Candida are azole-resistant, identifying the distributions of Candida species could facilitate the formulation of an appropriate empirical antifungal therapy. It has been shown that the distribution varies depending on the continent, country, city, and hospital. In this paper, we describe the distributions of species in hospitals in northern Osaka, Japan. METHOD: We evaluated blood culture results obtained from six tertiary hospitals in the northern Osaka area between 2004 and 2011. We also obtained comorbidity information from the patients' hospital medical records. Kaplan-Meier curves were drawn to compare the risk of death related to the different species. RESULTS: Of the 165 cases of candidemia confirmed by blood culture, 66% were male and the mean age was 62 years (range = 0-96). Overall, Candida albicans comprised 70 cases (43%), followed by Candida parapsilosis with 36 cases (22%), Candida glabrata with 25 cases (15%), Candida tropicalis with 11 cases (7%), Candida krusei with 10 cases (6%), and other Candida species with 13 cases (8%). C. tropicalis had higher associated mortality than other species, although it was not statistically significant. CONCLUSIONS: C. albicans was the most frequently isolated species, but the proportion of non-albicans Candida species was not negligible. The relatively high frequency of non-albicans Candida species distinguished the Japanese distribution from other areas. This characteristic distribution may have important implications when formulating an empirical antifungal therapy for Japanese clinical practice.

Upper Hemisternotomy Versus Full Sternotomy for Replacement of the Supracoronary Ascending Aorta and Aortic Valve.

OBJECTIVE: Upper hemisternotomy (UHS) for supracoronary ascending aorta replacement (scAAR) with concomitant aortic valve replacement (AVR) results in less trauma and potentially faster convalescence compared with full sternotomy (FS). Direct head-to-head studies are lacking. We compared a group of UHS patients with a matched group of FS patients undergoing scAAR and AVR. METHODS: There were 198 patients who underwent scAAR and AVR procedures by a single surgeon between 1999 and 2020. After matching 6 preoperative characteristics, there were 50 UHS and 50 FS patients. Patients who required acute type A aortic dissection repair, reoperations, concomitant procedures, or hypothermic circulatory arrest were excluded. RESULTS: In the matched sample, the hospital mortality rate was 1% (1 of 100). The median cardiopulmonary bypass time was 150 (interquartile range [IQR], 131 to 172) min and 164.5 (IQR, 138 to 190) min, respectively, for the UHS and FS groups (P = 0.08). The median aortic cross-clamp time was 121 (IQR, 107 to 139) min during UHS and 131 (IQR, 115 to 159) min during FS (P = 0.05). The median ventilation time was 7 (IQR, 3 to 14) h versus 17 (IQR, 10 to 24) h, respectively, after UHS and FS (P = 0.005). The median hospital length of stay was 7 (IQR, 6 to 9) days after UHS and 8 (IQR, 7 to 11) days after FS (P = 0.05). CONCLUSIONS: The low morbidity and mortality support the wider use of UHS for scAAR and AVR in appropriately selected patients. Larger studies are needed to confirm these initial findings.

Acute type A aortic syndromes: outcomes are independent of aortic root/valve management.

Purpose: Clinical outcomes following various surgical intervention strategies for aortic root and valve pathology during repair of acute type A aortic syndromes were studied and compared. Methods: From 2004 to 2019, 634 patients underwent acute type A aortic repair. Patients were divided into 4 groups: Valve Resuspension (n = 456), Isolated Valve Replacement (AVR) (n = 24), Valve and Root Replacement (ROOT) (n = 97), and Valve Sparing Root Replacement (VSRR) (n = 57). The primary endpoint was midterm survival and multivariable risk factor analysis was performed. Results: The mean age was 55.4 ± 13 years, 424 (67%) were male, and overall early mortality was 12%. Early mortality was 13%, 8%, 11%, and 7% for the Valve Resuspension, AVR, ROOT, and VSRR groups respectively, p = 0.43. Five-year survival was 74%, 86%, 73%, and 84% for the Valve Resuspension, AVR, ROOT, and VSRR groups respectively, p = 0.46. There was no difference in late stroke, renal failure, heart block, and late bleeding (p > 0.05 for all). At late follow-up, AVR and ROOT patients had a higher mean gradient versus Valve Resuspension and VSRR patients, p < 0.0001. For the total cohort, risk factors for late mortality included preoperative peripheral vascular disease (hazard ratio (HR) 2.3, 95% confidence interval (CI) 1.2-4.4, p = 0.009) and preoperative dialysis (HR 2.8, 95% CI 1.3-6.1, p = 0.01). Conclusion: Mid-term survival following repair of acute type A aortic dissection is not independently associated with a specific type of aortic valve intervention. Native valve preservation leads to acceptable mid-term valve hemodynamics and should be the preferred therapy in this emergent clinical setting. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-023-01602-8.

Vitamin D and prebiotics for intestinal health in cystic fibrosis: Rationale and design for a randomized, placebo-controlled, double-blind, 2 x 2 trial of administration of prebiotics and cholecalciferol (vitamin D3) (Pre-D trial) in adults with cystic fibrosis.

Individuals with cystic fibrosis (CF) have dysfunctional intestinal microbiota and increased gastrointestinal (GI) inflammation also known as GI dysbiosis. It is hypothesized that administration of high-dose cholecalciferol (vitamin D3) together with a prebiotic (inulin) will be effective, and possibly additive or synergistic, in reducing CF-related GI and airway dysbiosis. Thus, a 2 x 2 factorial design, placebo-controlled, double-blinded, pilot and feasibility, clinical trial was proposed to test this hypothesis. Forty adult participants with CF were block-randomized into one of four groups: 1) high-dose oral vitamin D3 (50,000 IU weekly) plus oral prebiotic placebo daily; 2) oral prebiotic (12 g inulin daily) plus oral placebo vitamin D3 weekly; 3) combined oral vitamin D3 weekly and oral prebiotic inulin daily; and 4) oral vitamin D3 placebo weekly and oral prebiotic placebo. The primary endpoints included 12-week changes in the microbial bacterial communities, gut and airway microbiota richness and diversity before and after the intervention. This pilot study examined whether vitamin D3 with or without prebiotics supplementation was feasible, changed airway and gut microbiota, and reduced dysbiosis, which in turn, may improve health outcomes and quality of life of patients with CF.

Vitamin D and Prebiotics for Intestinal Health in Cystic Fibrosis: Rationale and design for a randomized, placebo-controlled, double-blind, 2 × 2 trial of administration of prebiotics and cholecalciferol (vitamin D3) (Pre-D Trial) in adults with cystic fibrosis.

Individuals with cystic fibrosis (CF) have dysfunctional intestinal microbiota and increased gastrointestinal (GI) inflammation also known as GI dysbiosis. It is hypothesized that administration of high-dose cholecalciferol (vitamin D3) together with a prebiotic (inulin) will be effective, and possibly additive or synergistic, in reducing CF-related GI dysbiosis and improving intestinal functions. Thus, a 2 × 2 factorial design, placebo-controlled, double-blind, clinical trial was proposed to test this hypothesis. Forty adult participants with CF will be block-randomized into one of four groups: 1) high-dose oral vitamin D3 (50,000 IU weekly) plus oral prebiotic placebo daily; 2) oral prebiotic (12 g inulin daily) plus oral placebo vitamin D3 weekly; 3) combined oral vitamin D3 weekly and oral prebiotic inulin daily; and 4) oral vitamin D3 placebo weekly and oral prebiotic placebo. The primary endpoints will include 12-week changes in the reduced relative abundance of gammaproteobacteria, and gut microbiota richness and diversity before and after the intervention. This clinical study will examine whether vitamin D3 with or without prebiotics will improve intestinal health and reduce GI dysbiosis, which in turn, should improve health outcomes and quality of life of patients with CF.

Myocardial ischemia and angiotensin-converting enzyme inhibition: comparison of ischemia during mental and physical stress.

OBJECTIVE: Mental stress provokes myocardial ischemia in many patients with stable coronary artery disease (CAD). Mental stress-induced myocardial ischemia (MSIMI) portends a worse prognosis, independent of standard cardiac risk factors or outcome of traditional physical stress testing. Angiotensin II plays a significant role in the physiological response to stress, but its role in MSIMI remains unknown. Our aim was to evaluate whether the use of angiotensin-converting enzyme inhibitors (ACEIs) is associated with a differential effect on the incidence of MSIMI compared with ischemia during physical stress. METHODS: Retrospective analysis of 218 patients with stable CAD, including 110 on ACEI, was performed. 99m-Tc-sestamibi myocardial perfusion imaging was used to define ischemia during mental stress, induced by a standardized public speaking task, and during physical stress, induced by either exercise or adenosine. RESULTS: Overall, 40 patients (18%) developed MSIMI and 80 patients (37%) developed ischemia during physical stress. MSIMI occurred less frequently in patients receiving ACEIs (13%) compared with those not on ACEIs (24%; p = .030, adjusted odds ratio = 0.42, 95% confidence interval = 0.19-0.91). In contrast, the frequency of myocardial ischemia during physical stress testing was similar in both groups (39% versus 35% in those on and not on ACEIs, respectively); adjusted odds ratio = 0.91, 95% confidence interval = 0.48-1.73). CONCLUSION: In this retrospective study, patients using ACEI therapy displayed less than half the risk of developing ischemia during mental stress but not physical stress. This possible beneficial effect of ACEIs on MSIMI may be contributing to their salutary effects in CAD.

Effect of progenitor cell mobilization with granulocyte-macrophage colony-stimulating factor in patients with peripheral artery disease: a randomized clinical trial.

IMPORTANCE: Many patients with peripheral artery disease (PAD) have walking impairment despite therapy. Experimental studies in animals demonstrate improved perfusion in ischemic hind limb after mobilization of bone marrow progenitor cells (PCs), but whether this is effective in patients with PAD is unknown. OBJECTIVE: To investigate whether therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) improves exercise capacity in patients with intermittent claudication. DESIGN, SETTING, AND PARTICIPANTS: In a phase 2 double-blind, placebo-controlled study, 159 patients (median [SD] age, 64 [8] years; 87% male, 37% with diabetes) with intermittent claudication were enrolled at medical centers affiliated with Emory University in Atlanta, Georgia, between January 2010 and July 2012. INTERVENTIONS: Participants were randomized (1:1) to received 4 weeks of subcutaneous injections of GM-CSF (leukine), 500 µg/day 3 times a week, or placebo. Both groups were encouraged to walk to claudication daily. MAIN OUTCOMES AND MEASURES: The primary outcome was peak treadmill walking time (PWT) at 3 months. Secondary outcomes were PWT at 6 months and changes in circulating PC levels, ankle brachial index (ABI), and walking impairment questionnaire (WIQ) and 36-item Short-Form Health Survey (SF-36) scores. RESULTS: Of the 159 patients randomized, 80 were assigned to the GM-CSF group. The mean (SD) PWT at 3 months increased in the GM-CSF group from 296 (151) seconds to 405 (248) seconds (mean change, 109 seconds [95% CI, 67 to 151]) and in the placebo group from 308 (161) seconds to 376 (182) seconds (change of 56 seconds [95% CI, 14 to 98]), but this difference was not significant (mean difference in change in PWT, 53 seconds [95% CI, -6 to 112], P = .08). At 3 months, compared with placebo, GM-CSF improved the physical functioning subscore of the SF-36 questionnaire by 11.4 (95% CI, 6.7 to 16.1) vs 4.8 (95% CI, -0.1 to 9.6), with a mean difference in change for GM-CSF vs placebo of 7.5 (95% CI, 1.0 to 14.0; P = .03). Similarly, the distance score of the WIQ improved by 12.5 (95% CI, 6.4 to 18.7) vs 4.8 (95% CI, -0.2 to 9.8) with GM-CSF compared with placebo (mean difference in change, 7.9 [95% CI, 0.2 to 15.7], P = .047). There were no significant differences in the ABI, WIQ distance and speed scores, claudication onset time, or mental or physical component scores of the SF-36 between the groups. CONCLUSIONS AND RELEVANCE: Therapy with GM-CSF 3 times a week did not improve treadmill walking performance at the 3-month follow-up. The improvements in some secondary outcomes with GM-CSF suggest that it may warrant further study in patients with claudication. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01041417.

Secondary Analysis of a Dataset to Estimate the Prevalence of Vertebral Subluxation and Its Implications for Health Promotion and Prevention.

Background Vertebral subluxation (VS) is a clinical entity defined as a misalignment of the spine affecting biomechanical and neurological function. The identification and correction of VS is the primary focus of the chiropractic profession. The purpose of this study is to estimate VS prevalence using a sample of individuals presenting for chiropractic care and explore the preventative public health implications of VS through the promotion of overall health and function. Methodology A brief review of the literature was conducted to support an operational definition for VS that incorporated neurologic and kinesiologic exam components. A retrospective, quantitative analysis of a multi-clinic dataset was then performed using this operational definition. Descriptive statistics on patient demographic data included age, gender, and past health history characteristics. In addition to calculating estimates of the overall prevalence of VS, age- and gender-stratified estimates in the different clinics were calculated to allow for potential variations. Results A total of 1,851 patient records from seven chiropractic clinics in four states were obtained. The mean age of patients was 43.48 (SD = 16.8, range = 18-91 years). There were more females (n = 927, 64.6%) than males who presented for chiropractic care. Patients reported various reasons for seeking chiropractic care, including, spinal or extremity pain, numbness, or tingling; headaches; ear, nose, and throat-related issues; or visceral issues. Mental health concerns, neurocognitive issues, and concerns about general health were also noted as reasons for care. The overall prevalence of VS was 78.55% (95% CI = 76.68-80.42). Female and male prevalence of VS was 77.17% and 80.15%, respectively; notably, all per-clinic, age, or gender-stratified prevalences were ≥50%. Conclusions To date, this is the first study of its magnitude and application of an operational definition to estimate the prevalence of VS. Albeit nonrandom, the sample had a broad geographic distribution. The results of this study suggest a high rate of prevalence of VS in a sample of individuals who sought chiropractic care. Concerns about general health and wellness were represented in the sample and suggest chiropractic may serve a primary prevention function in the absence of disease or injury. Further investigation into the epidemiology of VS and its role in health promotion and prevention is recommended.

Mastering the Learning Curve for Robotic-Assisted Coronary Artery Bypass Surgery.

BACKGROUND: Previous studies have evaluated the learning curve to achieve competency in robotic-assisted coronary artery bypass grafting (CABG) but have not identified thresholds for mastery. Robotic-assisted CABG is a minimally invasive alternative to sternotomy CABG. The purpose of this study was to evaluate the short- and long-term outcomes of this procedure and to estimate the threshold for achieving mastery. METHODS: From 2009 to 2020, 1000 robotic-assisted CABG procedures were performed at a single institution. Robotic left internal mammary artery (LIMA) harvest followed by off-pump, LIMA-left anterior descending artery grafting using a 4-cm thoracotomy was performed. Short-term outcomes were obtained from The Society of Thoracic Surgeons database, and long-term follow-up was obtained by telephone questionnaires from dedicated research nurses for all patients more than 1 year from surgery. RESULTS: Mean patient age was 64 ± 11 years, Society of Thoracic Surgeons predicted risk of mortality was 1.1% ± 1.5%, and 76% (758) of patients were men. Thirty-day mortality occurred in 6 patients (0.6%; observed-to-expected ratio, 0.53), 5 patients (0.5%) experienced a postoperative stroke, and postoperative LIMA patency was 97.2% (491/505). Mean procedure time decreased from 195 minutes to 176 minutes, and conversion to sternotomy decreased from 4.4% (22/500) to 1.6% (8/500) after 500 cases. Short-term outcomes suggested expertise was reached between 250 and 500 cases. Long-term follow-up was completed in 97% of patients (873/896) with a median follow-up of 3.9 years (interquartile range, 1.8-5.8), and the overall survival rate was 89% (777). CONCLUSIONS: Robotic-assisted CABG can be performed safely with excellent results even during a surgeon's early experience. However the learning curve to achieve mastery is longer than required to achieve competency, with a threshold of approximately 250 to 500 cases.