Cleveland Clinic
  • Cleveland, OH, United States
Recent publications
Cardiac magnetic resonance (CMR) is the gold standard noninvasive imaging modality to assess tissue characteristics in vivo which gives it a unique advantage in discriminating benign cardiac masses from malignant tumors. CMR also provides visualization of tumor invasion, hemodynamic effects, and location relative to surrounding cardiac and extracardiac structures. These features make CMR an essential tool for diagnosis and management of cardiac tumors. The following sequences form part of a comprehensive CMR exam: cine imaging (e.g. balanced steady-state free precession (bSSFP)), T1/T2-weighted black-blood (BB) images, T1/T2 mapping, first-pass perfusion, and delayed enhancement imaging. The characteristics of the tumor are often described as hyper/iso/hypo-intense, meaning higher, equal to, or lower signal intensity compared to normal myocardium. For instance, the extensive vascular networks associated with malignant tumors often present as hyperintense on first-pass perfusion and on late gadolinium enhancement (LGE) images. The high volume of intracellular free water content in malignant tumors and the frequently observed surrounding edema may lead to longer T1 and T2 relaxation times. At the same time, necrosis and hemorrhage within the tumor often result in heterogeneous signal on T1W and T2W BB images. The newer T1 and T2 mapping techniques provide quantitative T1 and T2 values, instead of the relative grayscale obtained through T1W and T2W BB imaging, providing an opportunity to further advance the diagnosis of malignant cardiac tumors.
Background Performance benchmarks for the management of idiopathic pulmonary fibrosis (IPF) have not been established. We used data from the IPF-PRO Registry, an observational registry of patients with IPF managed at sites across the US, to examine associations between the characteristics of the enrolling sites and patient outcomes. Methods An online survey was used to collect information on the resources, operations, and self-assessment practices of IPF-PRO Registry sites that enrolled ≥ 10 patients. Site variability in 1-year event rates of clinically relevant outcomes, including death, death or lung transplant, and hospitalization, was assessed. Models were adjusted for differences in patient case mix by adjusting for known predictors of each outcome. We assessed whether site-level heterogeneity existed for each patient-level outcome, and if so, we investigated potential drivers of the heterogeneity. Results All 27 sites that enrolled ≥ 10 patients returned the questionnaire. Most sites were actively following > 100 patients with IPF (70.4%), had a lung transplant program (66.7%), and had a dedicated ILD nurse leader (77.8%). Substantial heterogeneity was observed in the event rates of clinically relevant outcomes across the sites. After controlling for patient case mix, there were no outcomes for which the site variance component was significantly different from 0, but the p-value for hospitalization was 0.052. Starting/completing an ILD-related quality improvement project in the previous 2 years was associated with a lower risk of hospitalization (HR 0.60 [95% CI 0.44, 0.82]; p = 0.001). Conclusions Analyses of data from patients with IPF managed at sites across the US found no site-specific characteristics or practices that were significantly associated with clinically relevant outcomes after adjusting for patient case mix. Trial registration ClinicalTrials.gov, NCT01915511. Registered 5 August 2013, https://clinicaltrials.gov/ct2/show/NCT01915511
Background: Dental personnel are at risk of developing occupational contact dermatitis. Objectives: The aims of the study were to determine prevalence of occupational contact dermatitis in dental personnel referred for patch testing and to characterize relevant allergens and sources. Methods: The study used a retrospective, cross-sectional analysis of the North American Contact Dermatitis Group (NACDG) data, 2001-2018. Results: Of 41,109 patients, 585 (1.4%) were dental personnel. Dental personnel were significantly more likely than nondental personnel to be female (75.7% vs 67.4%, P < 0.0001), have occupationally related dermatitis (35.7% vs 11.5%, P < 0.0001), and/or have primary hand involvement (48.6% vs 22.5%, P < 0.0001). More than one quarter of dental personnel (62/585, 27.7%) had 1 or more occupationally related allergic patch test reaction(s). There were 249 occupationally related reactions to NACDG screening allergens, most commonly glutaraldehyde (18.1%), thiuram mix (16.1%), and carba mix (14.1%). The most common sources of NACDG screening allergens were gloves (30.7%), dental materials (26.6%), and sterilizing solutions (13.1%). Seventy-three dental personnel (12.5%) had 1 or more positive patch test reactions to occupationally related allergen(s)/substances not on the screening series. Occupationally related irritant contact dermatitis was identified in 22.2% (n = 130) of dental personnel, most commonly to nonskin soaps/detergents/disinfectants (32.0%). Conclusions: Occupational contact dermatitis is common in dental personnel referred for patch testing. Comprehensive testing beyond screening series is important in these patients.
Background: Significant aortic regurgitation (AR) leads to left ventricular (LV) remodeling; however, little data exist regarding sex-based differences in LV remodeling in this setting. We sought to compare LV remodeling and AR severity, assessed by echocardiography and cardiovascular magnetic resonance (CMR), to discern sex-based differences. Methods: Patients with ≥ moderate chronic AR by echocardiography who underwent CMR within 90 days between December 2005 and October 2015 were included. Nonlinear regression models were built to assess the effect of AR regurgitant fraction (RF) on LV remodeling. A generalized linear model and Bland Altman analyses were constructed to evaluate differences between CMR and echocardiography. Referral for surgical intervention based on symptoms and LV remodeling was evaluated. Results: Of the 243 patients (48.3 ± 16.6 years, 58 (24%) female), 119 (49%) underwent surgical intervention with a primary indication of severe AR, 97 (82%) men, 22 (18%) women. Significant sex differences in LV remodeling emerged on CMR. Women demonstrated significantly smaller LV end-diastolic volume index (LVEDVI) (96.8 ml/m2 vs 125.6 ml/m2, p < 0.001), LV end-systolic volume index (LVESVI) (41.1 vs 54.5 ml/m2, p < 0.001), blunted LV dilation in the setting of increasing AR severity (LVEDVI p value < 0.001, LVESVI p value 0.011), and LV length indexed (8.32 vs 9.69 cm, p < 0.001). On Bland Altman analysis, a significant interaction with sex and LV diameters was evident, demonstrating a significant increase in the difference between CMR and echocardiography measurements as the LV enlarged in women: LVEDVI (p = 0.006), LVESVI (p < 0.001), such that echocardiographic measurements increasingly underestimated LV diameters in women as the LV enlarged. LV length was higher for males with a linear effect from RF (p < 0.001), with LV length increasing at a higher rate with increasing RF for males compared to females (two-way interaction with sex p = 0.005). Sphericity volume index was higher for men after adjusting for a relative wall thickness (p = 0.033). Conclusions: CMR assessment of chronic AR revealed significant sex differences in LV remodeling and significant echocardiographic underestimation of LV dilation, particularly in women. Defining optimal sex-based CMR thresholds for surgical referral should be further developed. Trial registration: NA.
PTEN hamartoma tumor syndrome (PHTS), caused by germline PTEN mutations, has been associated with organ-specific cancers and autism spectrum disorder (ASD) and/or developmental delay (DD). Predicting precise clinical phenotypes in any one PHTS individual remains impossible. We conducted an untargeted metabolomics study on an age- and sex-matched series of PHTS individuals with ASD/DD, cancer, or both phenotypes. Using agnostic metabolomic-analyses from patient-derived lymphoblastoid cells and their spent media, we found 52 differentially abundant individual metabolites, 69 cell/media metabolite ratios, and 327 pair-wise metabotype (shared metabolic phenotype) ratios clearly distinguishing PHTS individuals based on phenotype. Network analysis based on significant metabolites pointed to hubs converging on PTEN-related insulin, MAPK, AMPK, and mTOR signaling cascades. Internal cross-validation of significant metabolites showed optimal overall accuracy in distinguishing PHTS individuals with ASD/DD versus those with cancer. Such metabolomic markers may enable more accurate risk predictions and prevention in individual PHTS patients at highest risk.
Background The aim of this systematic review was to describe the prognostic value of patient-reported outcome measures (PROMs) in adult heart-transplant (HT) patients. Methods A systematic search was performed on Ovid Medline, CINAHL Plus, Web of Science, and PubMed. The study protocol was registered on the PROSPERO database (CRD42021225398), and the last search was performed on January 7, 2021. We included studies of adult HT patients where generic and disease-specific PROMs were used as prognostic indicators for survival, readmissions, HT complications, and the onset of new comorbidities. We excluded studies that used clinician-reported and patient-experience outcomes. The Quality in Prognosis Studies tool (QUIPS) was used to measure the risk of bias of the included studies. Results We included five observational studies between 1987 and 2015, whose populations’ mean age ranged from 43 to 56 years and presented a higher proportion of males than females. The Kansas City Cardiomyopathy Questionnaire demonstrated a negative correlation with readmissions (coefficient = − 1.177, p = 0.031), and the EQ-5D showed a negative correlation with the onset of neuromuscular disease after HT (coefficient = − 0.158, p < 0.001). The Millon Behavioral Health Inventory and the Nottingham Health Profile demonstrated a statistically significant association as survival predictors ( p = 0.002 and p < 0.05, respectively). A moderate overall risk of bias was reported in three studies, one study resulted in a low risk of bias, and a proportion of more than 75% of males in each of the studies. High heterogeneity between the studies impeded establishing a link between PROMs and prognostic value. Conclusion There is low evidence supporting PROMs usage as prognostic tools in adult HT patients. Comparing outcomes of PROMS to routine prognostic in wider and systematic settings is warranted. Systematic use of PROMs in clinical settings is warranted.
Background Alternative noninvasive methods capable of excluding intracranial hypertension through use of transcranial Doppler (ICP tcd ) in situations where invasive methods cannot be used or are not available would be useful during the management of acutely brain-injured patients. The objective of this study was to determine whether ICP tcd can be considered a reliable screening test compared to the reference standard method, invasive ICP monitoring (ICP i ), in excluding the presence of intracranial hypertension. Methods This was a prospective, international, multicenter, unblinded, diagnostic accuracy study comparing the index test (ICP tcd ) with a reference standard (ICP i ), defined as the best available method for establishing the presence or absence of the condition of interest (i.e., intracranial hypertension). Acute brain-injured patients pertaining to one of four categories: traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH) or ischemic stroke (IS) requiring ICP i monitoring, were enrolled in 16 international intensive care units. ICP i measurements (reference test) were compared to simultaneous ICP tcd measurements ( index test) at three different timepoints: before, immediately after and 2 to 3 h following ICP i catheter insertion. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated at three different ICP i thresholds (> 20, > 22 and > 25 mmHg) to assess ICP tcd as a bedside real-practice screening method. A receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC) was used to evaluate the discriminative accuracy and predictive capability of ICP tcd. Results Two hundred and sixty-two patients were recruited for final analysis. Intracranial hypertension (> 22 mmHg) occurred in 87 patients (33.2%). The total number of paired comparisons between ICP tcd and ICP i was 687. The NPV was elevated (ICP > 20 mmHg = 91.3%, > 22 mmHg = 95.6%, > 25 mmHg = 98.6%), indicating high discriminant accuracy of ICP tcd in excluding intracranial hypertension. Concordance correlation between ICP tcd and ICP i was 33.3% (95% CI 25.6–40.5%), and Bland–Altman showed a mean bias of -3.3 mmHg. The optimal ICP tcd threshold for ruling out intracranial hypertension was 20.5 mmHg, corresponding to a sensitivity of 70% (95% CI 40.7–92.6%) and a specificity of 72% (95% CI 51.9–94.0%) with an AUC of 76% (95% CI 65.6–85.5%). Conclusions and relevance ICP tcd has a high NPV in ruling out intracranial hypertension and may be useful to clinicians in situations where invasive methods cannot be used or not available. Trial registration : NCT02322970 .
Advances in cardiac surgical operative techniques and myocardial protection have dramatically improved outcomes in the past two decades. An unfortunate and unintended consequence is that 80% of the preventable morbidity and mortality following cardiac surgery now originates outside of the operating room. Our hope is that a renewed emphasis on evidence-based best practice and standardized perioperative care will reduce overall morbidity and mortality and improve patient-centric care. The Perioperative Quality Initiative (POQI) and Enhanced Recovery After Surgery–Cardiac Society (ERAS® Cardiac) have identified significant evidence gaps in perioperative medicine related to cardiac surgery, defined as areas in which there is significant controversy about how best to manage patients. These five areas of focus include patient blood management, goal-directed therapy, acute kidney injury, opioid analgesic reduction, and delirium.
Background In 2015, the United Nations adopted the Sustainable Development Goals (SDGs) as key priorities to improve the global health and international development agenda in an intersectoral manner, highlighting 17 SDGs. Six billion people lack access to safe, timely, and affordable cardiac surgical care due to capacity, geographic, and financial barriers. Nevertheless, cardiac surgery is largely disregarded on the global health agenda. In this review, we explore the intersection between cardiac surgery and the SDGs to delineate potential policy and advocacy avenues for the cardiothoracic surgical community. Main body A narrative review was performed using the PubMed/MEDLINE, Scopus, and WHO databases with variations of the search terms “cardiac surgery,” “cardiovascular diseases,” and keywords extracted from individual SDGs. All SDGs were manually reviewed to define intersectionality with global cardiac surgery. Out of 17 SDGs, 15 are relevant and require additional attention from the cardiovascular community. SDG3, “Good Health and Well-being,” is the most relevant, although the intersection between global cardiac surgery and other SDGs is apparent. A call for interdisciplinary collaboration through increased preventive mechanisms, rigorous, all-inclusive clinical trials, advocacy with relevant legislators, and mobilizing capacity building mechanisms are made. Conclusion Meeting the SDGs will require recognition of cardiovascular disease management, including cardiac surgical care. Cardiac surgeons are essential stakeholders of multidisciplinary collaborations working to improve access to safe, timely, and affordable cardiac surgery for all. Their role as advocates will be vital to establish local, national, regional, and international partnerships and to ensure progress towards SDG attainment.
Septic shock remains a health care concern associated with significant morbidity and mortality. The Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock recommend early fluid resuscitation and antimicrobials. Beyond initial management, the guidelines do not provide clear recommendations on appropriate time to initiate vasoactive therapies and corticosteroids in patients who develop shock. This review summarizes the literature regarding time of initiation of these interventions. Clinical data regarding time of initiation of these therapies in relation to shock onset, sequence of treatments with regard to each other, and clinical markers evaluated to guide initiation are summarized. Early-high vasopressor initiation within first 6 h of shock onset is associated with lower mortality. Following norepinephrine initiation, the exact dose and timing of escalation to adjunctive vasopressor agents are not well elucidated in the literature. However, recent data indicate that timing may be an important factor in initiating vasopressors and adjunctive therapies, such as corticosteroids. Norepinephrine-equivalent dose and lactate concentration can aid in determining when to initiate vasopressin and angiotensin II in patients with septic shock. Future guidelines with clear recommendations on the time of initiation of septic shock therapies are warranted.
Background Increasing evidence indicates the potential benefits of restricted fluid management in critically ill patients. Evidence lacks on the optimal fluid management strategy for invasively ventilated COVID-19 patients. We hypothesized that the cumulative fluid balance would affect the successful liberation of invasive ventilation in COVID-19 patients with acute respiratory distress syndrome (ARDS). Methods We analyzed data from the multicenter observational ‘PRactice of VENTilation in COVID-19 patients’ study. Patients with confirmed COVID-19 and ARDS who required invasive ventilation during the first 3 months of the international outbreak (March 1, 2020, to June 2020) across 22 hospitals in the Netherlands were included. The primary outcome was successful liberation of invasive ventilation, modeled as a function of day 3 cumulative fluid balance using Cox proportional hazards models, using the crude and the adjusted association. Sensitivity analyses without missing data and modeling ARDS severity were performed. Results Among 650 patients, three groups were identified. Patients in the higher, intermediate, and lower groups had a median cumulative fluid balance of 1.98 L (1.27–7.72 L), 0.78 L (0.26–1.27 L), and − 0.35 L (− 6.52–0.26 L), respectively. Higher day 3 cumulative fluid balance was significantly associated with a lower probability of successful ventilation liberation (adjusted hazard ratio 0.86, 95% CI 0.77–0.95, P = 0.0047). Sensitivity analyses showed similar results. Conclusions In a cohort of invasively ventilated patients with COVID-19 and ARDS, a higher cumulative fluid balance was associated with a longer ventilation duration, indicating that restricted fluid management in these patients may be beneficial. Trial registration Clinicaltrials.gov ( NCT04346342 ); Date of registration: April 15, 2020. Graphical abstract
Background Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs. Methods Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021). Results This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation. Conclusions This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease. ClinicalTrials.gov Identifier : NCT00628745.
Abstract Transthoracic echocardiography (TTE) is widely utilised within many aspects of clinical practice, as such the demand placed on echocardiography services is ever increasing. In an attempt to provide incremental value for patients and standardise patient care, the British Society of Echocardiography in collaboration with the British Heart Valve Society have devised updated guidance for the indications and triaging of adult TTE requests for TTE services to implement into clinical practice.
Background The self-assembling process of cartilage tissue engineering is a promising technique to heal cartilage defects, preventing osteoarthritic changes. Given that chondrocytes dedifferentiate when expanded, it is not known if cellular expansion affects the development of self-assembled neocartilage. The objective of this study was to use proteomic, mechanical, and biochemical analyses to quantitatively investigate the development of self-assembled neocartilage derived from passaged, rejuvenated costal chondrocytes. Methods Yucatan minipig costal chondrocytes were used to create self-assembled neocartilage constructs. After 1, 4, 7, 14, 28, 56, or 84 days of self-assembly, constructs were analyzed through a variety of histological, biomechanical, biochemical, and proteomic techniques. Results It was found that temporal trends in neocartilage formation are similar to those seen in native hyaline articular cartilage development. For example, between days 7 and 84 of culture, tensile Young’s modulus increased 4.4-times, total collagen increased 2.7-times, DNA content decreased 69.3%, collagen type II increased 1.5-times, and aggrecan dropped 55.3%, mirroring trends shown in native knee cartilage. Importantly, collagen type X, which is associated with cartilage calcification, remained at low levels (≤ 0.05%) at all neocartilage developmental time points, similar to knee cartilage (< 0.01%) and unlike donor rib cartilage (0.98%). Conclusions In this work, bottom-up proteomics, a powerful tool to interrogate tissue composition, was used for the first time to quantify and compare the proteome of a developing engineered tissue to a recipient tissue. Furthermore, it was shown that self-assembled, costal chondrocyte-derived neocartilage is suitable for a non-homologous approach in the knee.
Introduction De-escalation of breast cancer treatment aims to reduce patient and financial toxicity without compromising outcomes. Level I evidence and National Comprehensive Cancer Network guidelines support omission of adjuvant radiation in patients aged >70 y with hormone-sensitive, pT1N0M0 invasive breast cancer treated with endocrine therapy. We evaluated radiation use in patients eligible for guideline concordant omission of radiation. Methods Subgroup analysis of patients eligible for radiation omission from two pooled randomized controlled trials, which included stage 0-III breast cancer patients undergoing breast conserving surgery, was performed to evaluate factors associated with radiation use. Results Of 631 patients, 47 (7.4%) met radiation omission criteria and were treated by 14 surgeons at eight institutions. The mean age was 75.3 (standard deviation + 4.4) y. Majority of patients identified as White (n = 46; 97.9%) and non-Hispanic (n = 44; 93.6%). The mean tumor size was 1.0 cm; 37 patients (88.1%) had ductal, 4 patients (9.5%) had lobular, and 17 patients (40.5%) had low-grade disease. Among patients eligible for radiation omission, 34 (72.3%) patients received adjuvant radiation. Those who received radiation were significantly younger than those who did not (74 y, interquartile range = 4 y, versus 78 y, interquartile range = 11 y, P = 0.03). There was no difference in radiation use based on size (P = 0.4), histology (P = 0.5), grade (P = 0.7), race (P = 1), ethnicity (P = 0.6), institution (P = 0.1), gender of the surgeon (P = 0.7), or surgeon (P = 0.1). Conclusions Fewer than 10% of patients undergoing breast conservation met criteria for radiation omission. Nearly three-quarters received radiation therapy with younger age being a driver of radiation use, suggesting ample opportunity for de-escalation, particularly among younger eligible patients.
Background Substantial differences exist in the approach to resuscitating infants born at periviable gestation. Evaluation of current survival may help guide prenatal counselling and provide accurate expectations of clinical outcomes. We aimed to assess the US national survival trends in periviable infants born at gestational age (GA) ≤24 weeks. Methods We used de-identified patient data obtained from the US Healthcare Cost and Utilization Project (HCUP) from 2007 to 2018. All infants with documented GA ≤24 weeks were included. The Cochran-Armitage test was used for trend analyses. Regression analyses were conducted for variables associated with survival. Findings A total of 44,628,827 infant records were identified with 124,345 (0.28%) infants born ≤24 weeks; of those, 77,050 infants <24 weeks and 47,295 infants had completed 24 weeks. Survival rates for infants <24 weeks and with completed 24 weeks were 15.4% and 71.6%, respectively, with higher survival over the years (Z = 9.438, P<0.001 & Z = 3.30, P<0.001, respectively). Survival was lower in males compared to females (aOR = 0.96, CI: 0.93–0.99 & aOR = 0.94, CI: 0.92–0.96, respectively) and with private insurance compared to public insurance (aOR = 0.74, CI: 0.71–0.77 & aOR = 0.67, CI: 0.65–0.69, respectively). Survival was higher when birth weight was >500 g compared to ≤500 g (aOR = 4.62, CI:3.23–5.02 & aOR = 5.44, CI: 4.59–5.84, respectively). Black (aOR = 1.33, CI: 1.31–1.36 & aOR = 1.24, CI: 1.20–1.32, respectively) and Hispanic (aOR = 1.29, CI: 1.27–1.32 & aOR = 1.27, CI: 1.22–1.30, respectively) had higher survival than White. Interpretation There is a national increase in survival over the years in infants born at periviable GA. BW >500 is associated with >4 folds higher survival compared to ≤500 g. The results of this study should be cautiously interpreted as long-term outcomes are unknown Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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4,202 members
Roop K Kaw
  • Departments of Hospital Medicine; Anesthesiology Outcomes Research
Harpreet Kaur
  • Center for Neurological Restoration
Paul Schoenhagen
  • Cardiovascular Imaging
Salma Ben-Salem
  • Department of Cancer Biology
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9500 Euclid Avenue, 44195, Cleveland, OH, United States
Head of institution
Toby Cosgrove
Website
http://my.clevelandclinic.org/
Phone
800.223.2273