Patient characteristics, care patterns, and outcomes of atrial fibrillation associated hospitalizations in patients with chronic kidney disease and end-stage renal disease.

BACKGROUND: Chronic Kidney Disease (CKD) and end-stage renal disease (ESRD) are associated with poor outcomes in patients with cardiovascular disease. There is a paucity of contemporary data on in-hospital outcomes and care patterns of atrial fibrillation (AF) associated hospitalizations CKD and ESRD. METHODS: Outcomes and care patterns were evaluated in GWTG-AFIB database (Jan 2013-Dec 2018), including in-hospital mortality, use of a rhythm control strategy, and oral anticoagulation (OAC) prescription at discharge among eligible patients. Generalized logistic regression models with generalized estimating equations were used to ascertain differences in outcomes. Hospital-level variation in OAC prescription and rhythm control was also evaluated. RESULTS: Among 50,154 patients from 105 hospitals the median age was 70 years (interquartile range 61-79) and 47.3% were women. The prevalence of CKD was 36.0% while that of ESRD was 1.6%. Among eligible patients, discharge OAC prescription rates were 93.6% for CKD and 89.1% for ESRD. After adjustment, CKD and ESRD were associated with higher in-hospital mortality (odds ratio [OR] 3.08, 95% confidence interval [CI] 1.57-6.03 for ESRD and OR 2.02, 95% CI 1.52-2.67 for CKD), lower odds of OAC prescription at discharge (OR 0.59, 95% CI 0.44-0.79 for ESRD and OR 0.84, 95% CI 0.75-0.94 for CKD) compared with normal renal function. CKD was associated with lower utilization of rhythm control strategy (OR 0.92, 95% CI 0.87-0.98) with no significant difference between ESRD and normal renal function (OR 1.32, 95% CI 0.79-1.11). There was large hospital-level variation in OAC prescription at discharge (MOR 2.34, 95% CI 2.05-2.76) and utilization of a rhythm control strategy (MOR 2.69, 95% CI 2.34-3.21). CONCLUSIONS: CKD/ESRD is associated with higher in-hospital mortality, less frequent rhythm control, and less OAC prescription among patients hospitalized for AF. There is wide hospital-level variation in utilization of a rhythm control strategy and OAC prescription at discharge highlighting potential opportunities to improve care and outcomes for these patients, and better define standards of care in this patient population.

Epithelial organ shape is generated by patterned actomyosin contractility and maintained by the extracellular matrix.

Epithelial sheets define organ architecture during development. Here, we employed an iterative multiscale computational modeling and quantitative experimental approach to decouple direct and indirect effects of actomyosin-generated forces, nuclear positioning, extracellular matrix, and cell-cell adhesion in shaping Drosophila wing imaginal discs. Basally generated actomyosin forces generate epithelial bending of the wing disc pouch. Surprisingly, acute pharmacological inhibition of ROCK-driven actomyosin contractility does not impact the maintenance of tissue height or curved shape. Computational simulations show that ECM tautness provides only a minor contribution to modulating tissue shape. Instead, passive ECM pre-strain serves to maintain the shape independent from actomyosin contractility. These results provide general insight into how the subcellular forces are generated and maintained within individual cells to induce tissue curvature. Thus, the results suggest an important design principle of separable contributions from ECM prestrain and actomyosin tension during epithelial organogenesis and homeostasis.

Acute kidney injury after aortic valve replacement in a nationally representative cohort in the USA.

Background: Randomized trials have consistently shown lower rates of acute kidney injury (AKI) with transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve replacement (SAVR). Comparative rates of AKI for TAVR versus SAVR, and predictors and prognostic implications of AKI after aortic valve replacement (AVR) have not been well studied in nationally representative real-world data. Objectives: First, to compare rates of AKI and dialysis requiring AKI in TAVR versus SAVR. Second, to determine predictors of AKI and prognostic implications of AKI in patients undergoing TAVR or SAVR. Methods: We used the 2011-14 National Inpatient Sample to identify all patients undergoing isolated TAVR or SAVR using validated international classification of diseases, ninth revision ICD-9 codes. Rates of AKI and AKI requiring dialysis (AKI-D) were compared between the two groups using a propensity-matched design. Predictors of AKI and prognostic impact of AKI on in-hospital outcomes were ascertained using multivariate logistic regression. Results: A total of 8004 unweighted TAVR procedures and 29 355 unweighted SAVR procedures representative of 39 898 TAVR and 143 608 SAVR procedures nationwide were included in the analysis. Mean age of all patients undergoing AVR was 70.9 years and 42.3% were females. In a propensity-matched cohort of 4889 pairs of TAVR and SAVR procedures, TAVR was associated with significantly lower rates of AKI [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.66-0.80, P < 0.001] and AKI-D (OR 0.69, 95% CI 0.50-0.96, P = 0.03) compared with SAVR. AKI was associated with significantly higher rates of in-hospital mortality for TAVR (OR 7.16, 95% CI 5.52-9.29, P < 0.001) as well as SAVR (OR 9.43, 95% CI 7.71-11.55, P < 0.001). Conclusions: In a large propensity-matched cohort of TAVR and SAVR procedures, TAVR was associated with significantly lower rates of AKI and AKI-D compared with SAVR. AKI and AKI-D are predictors of poor in-hospital outcomes in TAVR as well as SAVR.

The Emerging Role of Mobile-Health Applications in the Management of Hypertension.

PURPOSE OF REVIEW: Mobile-health technology, frequently referred to as m-health, encompasses smartphone, tablet, or personal computer use in the management of chronic disease. There has been a rise in the number of commercially available smartphone applications and website-based platforms which claim to help patients manage hypertension. Very little research has been performed confirming whether or not use of these applications results in improved blood pressure (BP) outcomes. In this paper, we review existing literature on m-health systems and how m-health can affect hypertension management. RECENT FINDINGS: M-health systems help patients manage hypertension in the following ways: (1) setting alarms and reminders for patients to take their medications, (2) linking patients' BP reports to their electronic medical record for their physicians to review, (3) providing feedback to patients about their BP trends, and (4) functioning as point-of-care BP sensors. M-health applications with alarms and reminders can increase medication compliance while applications that share ambulatory BP data with patients' physicians can foster improved patient-physician dialog. However, the most influential tool for achieving positive BP outcomes appears to be patient-directed feedback about BP trends. A large number of commercially available m-health applications may facilitate self-management of hypertension by enhancing medication adherence, maintaining a log of blood pressure measurements, and facilitating physician-patient communication. A small number of applications function as BP sensors, thereby transforming the smartphone into a medical device. Such BP sensors often generate unreliable recordings. Patients must be cautioned regarding the use of smartphones for BP measurement at least until these applications have been more extensively validated.

Acute Pericarditis-Associated Hospitalization in the USA: A Nationwide Analysis, 2003-2012.

BACKGROUND AND OBJECTIVES: Epidemiologic data on hospitalizations for acute pericarditis are scarce. We sought to study the trends in these hospitalizations and outcomes in the USA over a 10-year period. METHODS: We used the 2003-2012 Nationwide Inpatient Sample database to identify admissions with a primary diagnosis of acute pericarditis. Outcomes included hospitalization rate, case fatality rate (CFR), length of stay (LOS), hospital charges, complications and diagnostic and therapeutic procedures. RESULTS: We observed an estimated 135,710 hospitalizations for acute pericarditis among patients ≥16 years during the study period (mean age 53.5 ± 18.5 years; 40.5% women). The incidence of acute pericarditis hospitalizations was significantly higher for men than for women [incidence rate ratio (IRR) 1.56; 95% confidence interval (CI) 1.54-1.58; p < 0.001]; it decreased from 66 to 54 per million person-years (p < 0.001). CFR and LOS declined significantly during the study period (CFR: 2.2% in 2003 to 1.4% in 2012; LOS: 4.8 days in 2003 to 4.1 days in 2012; p < 0.001 for both). The average inflation-adjusted health-care charge increased from USD 31,242 to 38,947 (p < 0.001). CONCLUSION: The hospitalization rate, CFR and LOS associated with acute pericarditis have declined significantly in the US population. Average charges for acute pericarditis hospitalization have increased.

Racial Differences in Outcomes after Acute Ischemic Stroke Hospitalization in the United States.

BACKGROUND AND OBJECTIVES: Racial differences in stroke outcomes have major health policy implications. There is paucity of contemporary data on racial differences in clinical outcomes and resource utilization in acute ischemic stroke hospitalizations in the United States. METHODS: We used the 2011-2012 National Inpatient Sample to identify hospitalizations with a primary diagnosis of acute ischemic stroke. Primary outcomes were in-hospital mortality, utilization of thrombolysis, and endovascular mechanical thrombectomy (EMT). Secondary outcomes were length of stay (LOS) and average inflation-adjusted charges. RESULTS: A total of 173,910 hospitalizations representing 835,811 hospitalizations nationwide were included in the study. Mean age was 70.9 years and 52.3% were women. Blacks (adjusted OR .71, 95% CI .64-.78, P < .001) and Asian or Pacific Islanders (adjusted OR .80, 95% CI .66-.97, P = .02) had a lower in-hospital mortality compared to Whites. Blacks were less likely to be treated with thrombolysis (adjusted OR .84, 95% CI .76-.92, P < .001) and EMT (OR .73, 95% CI .58-.91, P = .01). Average LOS and inflation-adjusted charges were significantly higher for racial minorities compared to Whites. CONCLUSIONS: Blacks and Asians hospitalized for ischemic stroke are less likely to die in the hospital compared to Whites. Hospitalization for stroke in Blacks is associated with lower rates of reperfusion therapy, longer lengths of stay, and higher costs compared to Whites.

YouTube as a source of information on dialysis: a content analysis.

AIM: End-stage renal disease is a prevalent and growing health problem worldwide. With increasing Internet use, video-sharing websites could potentially serve as a powerful platform for dissemination of information on dialysis. We conducted a cross-sectional study to assess the accuracy, content and viewership of YouTube videos on dialysis. METHODS: YouTube videos identified using the search term 'dialysis' were classified independently by two physicians as 'useful,' 'misleading' and 'patient's personal experiences'. Five-point ordinal scales were used to grade reliability and quality. Information regarding source of upload, content in seven pre-defined domains and various viewer interaction metrics was collected. RESULTS: Of the 115 videos with cumulative duration of 16.2 h and viewership of approximately 2.7 million, 67 (58.3%) were useful, 19 (16.5%) were misleading and 29 (25.2%) represented patient's personal experiences; kappa statistic for inter-observer agreement was 0.985. Useful videos were the most comprehensive and had the highest reliability and quality scores. However, viewership per day was the lowest for useful videos at a median of 3 (interquartile range (IQR) 1-17), as compared with 11 (IQR 4-43) for misleading videos and 14 (IQR 5-30) for patient experiences (P = 0.013). All misleading videos were uploaded by individual users with unknown credentials. Of these, 68.4% promoted alternative therapies such as herbs and osmotherapy; 47.4% included advertisements for related services. CONCLUSIONS: Viewers favoured misleading videos and patient narratives over scientifically accurate information. Authoritative sources should use popular social media websites to provide relevant and easy-to-understand information on dialysis; including patient stories can make this material more engaging.

Quantitative pedigree analysis and mitochondrial DNA sequence variants in adults with cyclic vomiting syndrome.

BACKGROUND: Children with cyclic vomiting syndrome (CVS) have a high degree of maternal inheritance of functional gastrointestinal and neurological disorders. CVS in children is also associated with an increased prevalence of mitochondrial DNA single-nucleotide polymorphisms (mtDNA SNPs) 16519 T and 3010A. Preliminary data suggests that age of onset of symptoms (pediatric vs. adult) may be a determinant of the presence of such mtDNA SNP's. We sought to examine the degree of maternal inheritance pattern of functional disorders and the prevalence of mtDNA SNP's16519T and 3010A in adults with CVS and correlate this with age of onset of disease. METHODS: A Quantitative Pedigree Analysis (QPA) was performed in 195 of a total of 216 patients and all were genotyped using Restriction Fragment Length Polymorphism (RFLP) or sequencing. RESULTS: Adults with CVS had a higher degree of probable maternal inheritance (PMI) of functional disorders than controls (12% vs. 1%, p < 0.001). However, the prevalence of mitochondrial SNP's 16519 T, 3010A and the AT genotype were similar in Haplogroup H CVS patients compared to historical controls. There was no correlation between age of onset of disease and prevalence of these mtDNA SNP's. CONCLUSIONS: A subset of adults with CVS has a significantly higher degree of maternal inheritance pattern of functional disorders than controls. There was no association with mtDNA SNP's 16519 T and 3010A as seen in children and future studies sequencing the entire mitochondrial and nuclear genome to identify potential causes for this maternal inheritance pattern in adults are warranted.

Reverse engineering morphogenesis through Bayesian optimization of physics-based models.

Morphogenetic programs coordinate cell signaling and mechanical interactions to shape organs. In systems and synthetic biology, a key challenge is determining optimal cellular interactions for predicting organ shape, size, and function. Physics-based models defining the subcellular force distribution facilitate this, but it is challenging to calibrate parameters in these models from data. To solve this inverse problem, we created a Bayesian optimization framework to determine the optimal cellular force distribution such that the predicted organ shapes match the experimentally observed organ shapes. This integrative framework employs Gaussian Process Regression, a non-parametric kernel-based probabilistic machine learning modeling paradigm, to learn the mapping functions relating to the morphogenetic programs that maintain the final organ shape. We calibrated and tested the method on Drosophila wing imaginal discs to study mechanisms that regulate epithelial processes ranging from development to cancer. The parameter estimation framework successfully infers the underlying changes in core parameters needed to match simulation data with imaging data of wing discs perturbed with collagenase. The computational pipeline identifies distinct parameter sets mimicking wild-type shapes. It enables a global sensitivity analysis to support the regulation of actomyosin contractility and basal ECM stiffness to generate and maintain the curved shape of the wing imaginal disc. The optimization framework, combined with experimental imaging, identified that Piezo, a mechanosensitive ion channel, impacts fold formation by regulating the apical-basal balance of actomyosin contractility and elasticity of ECM. This workflow is extensible toward reverse-engineering morphogenesis across organ systems and for real-time control of complex multicellular systems.

Balancing competing effects of tissue growth and cytoskeletal regulation during Drosophila wing disc development.

How a developing organ robustly coordinates the cellular mechanics and growth to reach a final size and shape remains poorly understood. Through iterations between experiments and model simulations that include a mechanistic description of interkinetic nuclear migration, we show that the local curvature, height, and nuclear positioning of cells in the Drosophila wing imaginal disc are defined by the concurrent patterning of actomyosin contractility, cell-ECM adhesion, ECM stiffness, and interfacial membrane tension. We show that increasing cell proliferation via different growth-promoting pathways results in two distinct phenotypes. Triggering proliferation through insulin signaling increases basal curvature, but an increase in growth through Dpp signaling and Myc causes tissue flattening. These distinct phenotypic outcomes arise from differences in how each growth pathway regulates the cellular cytoskeleton, including contractility and cell-ECM adhesion. The coupled regulation of proliferation and cytoskeletal regulators is a general strategy to meet the multiple context-dependent criteria defining tissue morphogenesis.

Piezo regulates epithelial topology and promotes precision in organ size control.

Mechanosensitive Piezo channels regulate cell division, cell extrusion, and cell death. However, systems-level functions of Piezo in regulating organogenesis remain poorly understood. Here, we demonstrate that Piezo controls epithelial cell topology to ensure precise organ growth by integrating live-imaging experiments with pharmacological and genetic perturbations and computational modeling. Notably, the knockout or knockdown of Piezo increases bilateral asymmetry in wing size. Piezo's multifaceted functions can be deconstructed as either autonomous or non-autonomous based on a comparison between tissue-compartment-level perturbations or between genetic perturbation populations at the whole-tissue level. A computational model that posits cell proliferation and apoptosis regulation through modulation of the cutoff tension required for Piezo channel activation explains key cell and tissue phenotypes arising from perturbations of Piezo expression levels. Our findings demonstrate that Piezo promotes robustness in regulating epithelial topology and is necessary for precise organ size control.

Reverse engineering morphogenesis through Bayesian optimization of physics-based models.

Morphogenetic programs direct the cell signaling and nonlinear mechanical interactions between multiple cell types and tissue layers to define organ shape and size. A key challenge for systems and synthetic biology is determining optimal combinations of intra- and inter-cellular interactions to predict an organ's shape, size, and function. Physics-based mechanistic models that define the subcellular force distribution facilitate this, but it is extremely challenging to calibrate parameters in these models from data. To solve this inverse problem, we created a Bayesian optimization framework to determine the optimal cellular force distribution such that the predicted organ shapes match the desired organ shapes observed within the experimental imaging data. This integrative framework employs Gaussian Process Regression (GPR), a non-parametric kernel-based probabilistic machine learning modeling paradigm, to learn the mapping functions relating to the morphogenetic programs that generate and maintain the final organ shape. We calibrated and tested the method on cross-sections of Drosophila wing imaginal discs, a highly informative model organ system, to study mechanisms that regulate epithelial processes that range from development to cancer. As a specific test case, the parameter estimation framework successfully infers the underlying changes in core parameters needed to match simulation data with time series imaging data of wing discs perturbed with collagenase. Unexpectedly, the framework also identifies multiple distinct parameter sets that generate shapes similar to wild-type organ shapes. This platform enables an efficient, global sensitivity analysis to support the necessity of both actomyosin contractility and basal ECM stiffness to generate and maintain the curved shape of the wing imaginal disc. The optimization framework, combined with fixed tissue imaging, identified that Piezo, a mechanosensitive ion channel, impacts fold formation by regulating the apical-basal balance of actomyosin contractility and elasticity of ECM. This framework is extensible toward reverse-engineering the morphogenesis of any organ system and can be utilized in real-time control of complex multicellular systems.

The multimodal action of G alpha q in coordinating growth and homeostasis in the Drosophila wing imaginal disc.

Background: G proteins mediate cell responses to various ligands and play key roles in organ development. Dysregulation of G-proteins or Ca 2+ signaling impacts many human diseases and results in birth defects. However, the downstream effectors of specific G proteins in developmental regulatory networks are still poorly understood. Methods: We employed the Gal4/UAS binary system to inhibit or overexpress Gαq in the wing disc, followed by phenotypic analysis. Immunohistochemistry and next-gen RNA sequencing identified the downstream effectors and the signaling cascades affected by the disruption of Gαq homeostasis. Results: Here, we characterized how the G protein subunit Gαq tunes the size and shape of the wing in the larval and adult stages of development. Downregulation of Gαq in the wing disc reduced wing growth and delayed larval development. Gαq overexpression is sufficient to promote global Ca 2+ waves in the wing disc with a concomitant reduction in the Drosophila final wing size and a delay in pupariation. The reduced wing size phenotype is further enhanced when downregulating downstream components of the core Ca 2+ signaling toolkit, suggesting that downstream Ca 2+ signaling partially ameliorates the reduction in wing size. In contrast, Gαq -mediated pupariation delay is rescued by inhibition of IP 3 R, a key regulator of Ca 2+ signaling. This suggests that Gαq regulates developmental phenotypes through both Ca 2+ -dependent and Ca 2+ -independent mechanisms. RNA seq analysis shows that disruption of Gαq homeostasis affects nuclear hormone receptors, JAK/STAT pathway, and immune response genes. Notably, disruption of Gαq homeostasis increases expression levels of Dilp8, a key regulator of growth and pupariation timing. Conclusion: Gαq activity contributes to cell size regulation and wing metamorphosis. Disruption to Gαq homeostasis in the peripheral wing disc organ delays larval development through ecdysone signaling inhibition. Overall, Gαq signaling mediates key modules of organ size regulation and epithelial homeostasis through the dual action of Ca 2+ -dependent and independent mechanisms.

Clostridium difficile infection in hospitalized liver transplant patients: a nationwide analysis.

The incidence of Clostridium difficile infection (CDI) is increasing among hospitalized patients. Liver transplantation (LT) patients are at higher risk for acquiring CDI. Small, single-center studies (but no nationwide analyses) have assessed this association. We used the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project (2004-2008) for this retrospective, cross-sectional study. Patients with any discharge diagnosis of LT composed the study population, and they were identified with International Classification of Diseases, Ninth Revision, Clinical Modification codes. Those with a discharge diagnosis of CDI were considered cases. Our primary outcomes were the prevalence of CDI and the effects of CDI on inpatient mortality. Our secondary outcomes included the length of stay and hospitalization charges. A regression analysis was used to derive odds ratios (ORs) adjusted for potential confounders. There were 193,174 discharges with a diagnosis of LT from 2004 to 2008. The prevalence of CDI was 2.7% in the LT population and 0.9% in the non-LT population (P < 0.001). Most of the LT patients were 50 to 64 years old. LT patients had higher odds of developing CDI [OR = 2.88, 95% confidence interval (CI) = 2.68-3.10]. Increasing age and increasing comorbidity (including inflammatory bowel disease and nasogastric tube placement) were also independent CDI risk factors. CDI was associated with a higher mortality rate: 5.5% for LT patients with CDI versus 3.2% for LT-only patients (adjusted OR = 1.70, 95% CI = 1.29-2.25). In conclusion, the prevalence of CDI is higher for LT patients versus non-LT patients (2.7% versus 0.9%). CDI is an independent risk factor for mortality in the LT population.

Chronic kidney disease and end-stage renal disease predict higher risk of mortality in patients with primary upper gastrointestinal bleeding.

BACKGROUND: The outcome of gastrointestinal bleeding in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients is difficult to discern from the literature. Many publications are small, single-center series or are from an era prior to advanced interventional endoscopy, widespread use of proton pump inhibitors or treatment for Helicobacter pylori infections. In this study, we quantify the role of CKD and ESRD as independent predictors of mortality in patients admitted to the hospital with a principal diagnosis of primary upper gastrointestinal bleeding (UGIB). METHODS: We used the Nationwide Inpatient Sample that contains data on approximately 8 million admissions in 1,000 hospitals chosen to approximate a 20% stratified sample of all US facilities. Patients discharged with the principal diagnosis of primary UGIB, CKD or ESRD were identified through the ninth revision of the International Classification of Diseases, clinical modification (ICD-9-CM) codes. The outcome variables included frequency and in-hospital mortality of UGIB in CKD and ESRD patients as compared to non-CKD patients and were analyzed using logistic regression modeling. RESULTS: In 2007, out of a total of 398,213 admissions with a diagnosis of primary UGIB, 35,985 were in CKD, 14,983 in ESRD, and 347,245 in non-renal disease groups. The OR for primary UGIB hospitalization in CKD and ESRD was 1.30 (95% CI 1.17-1.46) and 1.84 (95% CI 1.61-2.09), respectively. The corresponding all-cause mortality OR was 1.47 (95% CI 1.21-1.78) and 3.02 (95% CI 2.23-4.1), respectively. CONCLUSION: Patients with CKD or ESRD admitted with primary UGIB have up to three times higher risk of all-cause in-hospital mortality, warranting heightened vigilance by their clinicians.

Cyclic Vomiting Syndrome (CVS): is there a difference based on onset of symptoms--pediatric versus adult?

BACKGROUND: Cyclic Vomiting Syndrome (CVS) is a well-recognized functional gastrointestinal disorder in children but its presentation is poorly understood in adults. Genetic differences in pediatric-onset (presentation before age 18) and adult-onset CVS have been reported recently but their clinical features and possible differences in response to therapy have not been well studied. METHODS: This was a retrospective review of 101 CVS patients seen at the Medical College of Wisconsin between 2006 and 2008. Rome III criteria were utilized to make the diagnosis of CVS. RESULTS: Our study population comprised of 29(29%) pediatric-onset and 72 (71%) adult-onset CVS patients. Pediatric-onset CVS patients were more likely to be female (86% vs. 57%, p = 0.005) and had a higher prevalence of CVS plus (CVS + neurocognitive disorders) as compared to adult-onset CVS patients (14% vs. 3%, p = 0.05). There was a longer delay in diagnosis (10 ± 7 years) in the pediatric-onset group when compared to (5 ± 7 years) adult-onset CVS group (p = 0.001). Chronic opiate use was less frequent in the pediatric-onset group compared to adult-onset patients (0% vs. 23%, p = 0.004). Aside from these differences, the two groups were similar with regards to their clinical features and the time of onset of symptoms did not predict response to standard treatment. The majority of patients (86%) responded to treatment with tricyclic antidepressants, anticonvulsants (topiramate), coenzyme Q-10, and L-carnitine. Non-response to therapy was associated with coalescence of symptoms, chronic opiate use and more severe disease as characterized by longer episodes, greater number of emergency department visits in the year prior to presentation, presence of disability and non-compliance on univariate analysis. On multivariate analysis, only compliance to therapy was associated with a response. (88% vs. 38%, Odds Ratio, OR 9.6; 95% Confidence Interval [CI], 1.18-77.05). CONCLUSION: Despite reported genetic differences, the clinical features and response to standard therapy in pediatric- and adult-onset CVS were mostly similar. Most patients (86%) responded to therapy and compliance was the only factor associated with a response.

Does the routine echocardiographic exam have a role in the detection and evaluation of cholelithiasis and gallbladder wall thickening?

Cholelithiasis is a very common disease in the United States. Most cases remain asymptomatic but a fraction of these patients can develop serious complications such as cholecystitis which may lead to gallbladder perforation and gallbladder cancer which is much less common. Here, we present three cases of cholelithiasis where transthoracic echocardiography was performed routinely. In each case, echocardiography detected cholelithiasis which prompted three-dimensional (3D) echocardiographic evaluation. Three-dimensional echocardiography allowed for more comprehensive examination of the gallbladder shape, size, and wall thickening and the measurement and composition of the stones in three dimensions, measurement of stone volumes, and minimized shadowing produced by stone calcifications. These cases suggest that routine echocardiography has value in detecting gallstones and that 3D echocardiography has incremental value over two-dimensional echocardiography due to pyramidal data sets which allow sequential slicing through the gallbladder and full gallbladder examination without a technologist who is trained in gallbladder imaging. These pyramidal data sets can be further viewed and cropped by a radiologist specialized in abdominal ultrasound.

MAPPER: An Open-Source, High-Dimensional Image Analysis Pipeline Unmasks Differential Regulation of Drosophila Wing Features.

Phenomics requires quantification of large volumes of image data, necessitating high throughput image processing approaches. Existing image processing pipelines for Drosophila wings, a powerful genetic model for studying the underlying genetics for a broad range of cellular and developmental processes, are limited in speed, precision, and functional versatility. To expand on the utility of the wing as a phenotypic screening system, we developed MAPPER, an automated machine learning-based pipeline that quantifies high-dimensional phenotypic signatures, with each dimension quantifying a unique morphological feature of the Drosophila wing. MAPPER magnifies the power of Drosophila phenomics by rapidly quantifying subtle phenotypic differences in sample populations. We benchmarked MAPPER's accuracy and precision in replicating manual measurements to demonstrate its widespread utility. The morphological features extracted using MAPPER reveal variable sexual dimorphism across Drosophila species and unique underlying sex-specific differences in morphogen signaling in male and female wings. Moreover, the length of the proximal-distal axis across the species and sexes shows a conserved scaling relationship with respect to the wing size. In sum, MAPPER is an open-source tool for rapid, high-dimensional analysis of large imaging datasets. These high-content phenomic capabilities enable rigorous and systematic identification of genotype-to-phenotype relationships in a broad range of screening and drug testing applications and amplify the potential power of multimodal genomic approaches.