Epidemiology, clinical features and outcomes of hospitalized patients with COVID-19 by vaccination status: a multicenter historical cohort study.

INTRODUCTION: COVID-19 disease resulted in over six million deaths worldwide. Although vaccines against SARS-CoV-2 demonstrated efficacy, breakthrough infections became increasingly common. There is still a lack of data regarding the severity and outcomes of COVID-19 among vaccinated compared to unvaccinated individuals. METHODS: This was a historical cohort study of adult COVID-19 patients hospitalized in five Ascension hospitals in southeast Michigan. Electronic medical records were reviewed. Vaccine information was collected from the Michigan Care Improvement Registry. Data were analyzed using Student's t-test, analysis of variance, the chi-squared test, the Mann-Whitney and Kruskal-Wallis tests, and multivariable logistic regression. RESULTS: Of 341 patients, the mean age was 57.9 ± 18.3 years, 54.8% (187/341) were female, and 48.7% (166/341) were black/African American. Most patients were unvaccinated, 65.7%, 8.5%, and 25.8% receiving one dose or at least two doses, respectively. Unvaccinated patients were younger than fully vaccinated (p = 0.001) and were more likely to be black/African American (p = 0.002). Fully vaccinated patients were 5.3 times less likely to have severe/critical disease (WHO classification) than unvaccinated patients (p < 0.001) after controlling for age, BMI, race, home steroid use, and serum albumin levels on admission. The case fatality rate in fully vaccinated patients was 3.4% compared to 17.9% in unvaccinated patients (p = 0.003). Unvaccinated patients also had higher rates of complications. CONCLUSIONS: Patients who were unvaccinated or partially vaccinated had more in-hospital complications, severe disease, and death as compared to fully vaccinated patients. Factors associated with severe COVID-19 disease included advanced age, obesity, low serum albumin, and home steroid use.

Evaluating Statin Tolerability in Historically Intolerant Patients After Correcting for Subclinical Hypothyroidism and Vitamin D Insufficiency.

INTRODUCTION: Atherosclerotic cardiovascular disease (ASCVD) is the major cause of morbidity and mortality worldwide. Statins provide primary and secondary ASCVD prevention. Intolerance due to statin-associated myalgias reduces long-term adherence, thus muting potential benefits. AIM: Our analysis sought to determine whether transition from a lipophilic statin to a water-soluble statin, or correction of subclinical hypothyroidism and/or vitamin D insufficiency/deficiency (metabolic abnormalities), improved statin tolerance. METHODS: We performed a retrospective analysis of the data from patients referred to our lipid clinic because of statin intolerance. Patients intolerant to a lipophilic statin were switched to a water-soluble statin. Patients having vitamin D insufficiency/deficiency or subclinical hypothyroidism were re-challenged with a water-soluble statin (or lipophilic statin with minimal systemic exposure) after correction of the metabolic abnormality. RESULTS: 169 patients were statin intolerant. 86% (n = 145) were white and 48% (n = 81) were male. 82 of these patients had one or both metabolic abnormalities. The remaining patients (n = 87) had no metabolic abnormality, however, were unable to tolerate a lipophilic statin. 72% (n = 73) of eligible patients (n = 101), defined as those with a corrected metabolic abnormality or without a metabolic abnormality on a lipophilic statin, were able to tolerate a water-soluble statin or lipophilic statin with minimal systemic exposure. In addition, 75% (n = 127) of this total cohort met their LDL-C goal. CONCLUSIONS: Our findings suggest that either correction of subclinical hypothyroidism and/or vitamin D insufficiency/deficiency or transition from a lipophilic statin to water-soluble statin (or lipophilic statin with minimal systemic exposure) improves statin tolerance.

Inferior Vena Cava Diameter Predicts Nephropathy in Patients Late After Fontan Palliation.

Single ventricle congenital heart defect patients have improved survival with Fontan palliation. However, they remain at risk for nephropathy, as indicated by pathologic microalbuminuria. We sought to investigate whether echocardiographic measures of the inferior vena cava diameter (a surrogate for elevated CVP) indexed to the body surface area (iIVC) or cardiac index (CI) can predict the presence of nephropathy in Fontan patients. We performed a single-center case-control study, including 39 asymptomatic Fontan (age 14.8 ± 7.9 years) and 29 healthy controls (age 12.7 ± 2.7 years). The primary outcome was abnormal microalbumin-creatinine ratio (MCR) from the first-morning void urine in Fontan patients. Measurements of iIVC and CI were derived using transthoracic echocardiography by two investigators with a high intra-class correlation coefficient (ICC = 0.97). Group comparison between Fontan and controls as well as between Fontan with normal and abnormal MCR was performed using Fisher's exact and t tests. Pearson and Spearman's correlations and multivariate regressions were performed to analyze the relations between the MCR, iIVC, and CI. Abnormal MCR was noted in 13/39(33%) of Fontan patients. The mean iIVC was larger in the Fontan compared to controls (p < 0.0001) and in Fontan with abnormal MCR compared to those with normal MCR (p = 0.0006). A positive correlation (r = 0.62; p < 0.001) was noted between MCR and iIVC. All patients with abnormal MCR had the iIVC > 1 cm/m2. There were no significant relations between the CI and MCR. Significant prevalence of nephropathy late after Fontan palliation warrents screening. Echocardiographic measurement of iIVC could serve as one of the screening measures. The finding of the iIVC diameter > 1 cm/m2 should prompt further renal evaluation.

Assessment and Management of Patients with Hyperlipidemia Referred for Initiation of PCSK9 Inhibitor Therapy: A Lipid Clinic Experience.

PURPOSE: Previous studies have reported that monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9) in clinical practice have been underutilized due to several barriers, including high cost, stringent insurance authorization, patient cost-sharing and insufficient documentation of a patient's medical history. The purpose of our study was to determine if prescribing PCSK9 inhibitors only to patients meeting the established indications would significantly improve the approval rate and utilization. METHODS: We conducted a review and analysis of the medical records of patients referred by their physician to a hospital-based lipid clinic over a 20-month period specifically for initiation of a PCSK9 inhibitor. RESULTS: There were 180 patients referred to our lipid clinic by their cardiologist or internist specifically for initiation of a PCSK9 inhibitor. Only 76 (42%) of these patients met the approved indications for this therapy and were provided PCSK9 inhibitor prescriptions. All received insurance approval within 3 weeks. Three did not initiate therapy due to excessive out-of-pocket cost, three discontinued therapy after two injections because of intolerable side effects (rhinorrhea), with the remaining 70 patients starting and continuing therapy, long-term. The remaining 104 patients were not given a PCSK9 inhibitor prescription and were treated with oral lipid-lowering medications. CONCLUSION: Our findings suggest that those physicians who referred patients to our lipid clinic specifically for initiation of a PCSK9 inhibitor were not aware of the established indications. By prescribing a PCSK9 inhibitor to only those patients meeting the established indications, 100% obtained approval. Therefore, to achieve higher insurance approval rates and utilization, it is essential that physicians understand the indications for PCSK9 inhibitor therapy and prescribe them only to patients meeting the established indications.

Cardiac Murmur in a Boy with Normal Paternal Prenatal Carrier Screening for Pompe Disease.

INTRODUCTION: Pompe disease is an autosomal recessive lysosomal storage disorder with marked morbidity and mortality, if untreated. With the advent of enzyme replacement therapy, it is essential to identify the infantile-type as early as possible to mitigate the effects of the enzyme deficiency. Identification is possible prenatally with testing of both parents. More recently, many states have instituted newborn screening for this condition. CASE: We report a patient with infantile-onset Pompe disease with a normal paternal carrier genetic test, born prior to newborn screening for Pompe disease in the state of Michigan. The infant's father was retested once the infant was diagnosed with Pompe disease postnatally and noted to have a mutation conducive to Pompe disease. CONCLUSION: Providers should have a strong clinical suspicion for disorders even if prenatal parental carrier screening is normal. A normal parental prenatal test does not exclude the possibility that the fetus may be diagnosed with a disorder postnatally, and pediatricians may be faced with limitations in accuracy of parents' recollection of parental testing results.

Radiation Exposure in Pediatric Intensive Care Unit Patients: How Much Is Too Much?

We aimed to determine median cumulative radiation exposure in pediatric intensive care unit (PICU) patients, proportion of patients with high radiation exposure (above annual average radiation per person of 6.2 mSv), and determine risk factors for high exposure. This was a retrospective chart review of PICU patients up to 18 years of age admitted to a large community hospital over 2 years. Radiologic studies and radiation exposure were determined for each patient, and total hospital radiation exposure was classified as high (>6.2 mSv) or not (≤6.2 mSv). Median radiation exposure per patient was 0.2 mSv (interquartile range = 2.1) and 11.7% of patients received >6.2 mSv radiation during their hospitalization. Factors associated with high radiation exposure included admission for trauma or surgery, number of computed tomography scans, age, and PICU length of stay (all P < .0001). We concluded that subsets of PICU patients are at risk of high radiation exposure. Policies and protocols may help minimize radiation exposure among PICU patients.

Yield of Echocardiogram and Predictors of Positive Yield in Pediatric Patients: A Study in an Urban, Community-Based Outpatient Pediatric Cardiology Clinic.

The yield of outpatient echocardiograms varies based on the indication for the echocardiogram and the age of the patient. The purpose of this study was to determine the cumulative yield of outpatient echocardiograms by age group and reason for the test. A secondary aim was to determine the predictors of a positive echocardiogram in an outpatient cardiology clinic at a large community teaching hospital. We retrospectively reviewed the charts of 891 patients who had a first-time echocardiogram between 2011 and 2015. Positive yield was defined as echocardiographic findings that explained the reason for the echocardiogram. The overall positive yield was 8.2%. Children between birth and 3 months of age had the highest yield (34.2%), and children between 12 and 18 years of age had the lowest yield (1%). Patients with murmurs (18.1%) had the highest yield compared with patients with other signs or symptoms. By age group and reason, the highest yields were as follows: 0 to 3 months of age, murmur (39.2%); 4 to 11 months of age, >1 symptom (50%); and 1 to 5 years of age, shortness of breath (66.7%). Based on our study, the overall yield of echocardiograms in the outpatient pediatric setting is low. Age and symptoms should be considered before ordering an echocardiogram.

Large pseudoaneurysm following right ventricle to pulmonary artery homograft placement in an infant.

Pseudoaneurysm (PSA) is a known but rare complication of the right ventricle to pulmonary artery (RV-PA) conduits. The patient's clinical presentation can be variable ranging from asymptomatic to potential rupture. We describe an unusual case of a massive PSA in an infant who underwent RV-PA pulmonary homograft placement after relief of right ventricular outflow tract obstruction.

Lysosomal acid lipase deficiency in all siblings of the same parents.

We present 4 normal-weight sibling children with lysosomal acid lipase deficiency (LAL-D). LAL-D was considered in the differential diagnosis based on the absence of secondary causes and primary inherited traits for their marked hyperlipidemia, together with unexplained hepatic transaminase elevation. Residual lysosomal acid lipase activity confirmed the diagnosis. DNA sequencing of LIPA indicated that the siblings were compound heterozygotes (c.894G>A and c.428+1G>A). This case describes the unusual occurrence of all offspring from the same nonconsanguineous mother and father inheriting compound heterozygosity of a recessive trait and the identification of an apparently unique LIPA mutation (c.428+1G>A). It highlights the collaborative effort between a lipidologist and gastroenterologist in developing a differential diagnosis leading to the confirmatory diagnosis of this rare, life-threatening disease. With the availability of an effective enzyme replacement therapy (sebelipase alfa), LAL-D should be entertained in the differential diagnosis of children, adolescents, and young adults with idiopathic hyperlipidemia and unexplained hepatic transaminase elevation.

Tissue Doppler Imaging and Focal, Late-Onset Anthracycline-Induced Cardiovascular Disease in Long Term Survivors of Childhood Cancer: A Research Article.

INTRODUCTION: In anthracycline-induced cardiomyopathy, the onset of diastolic dysfunction occurs before systolic dysfunction. Although, conventional echocardiogram is the standard method to assess cardiac function post anthracycline therapy, Tissue Doppler Imaging (TDI) may detect early onset cardiac diastolic dysfunction among anthracycline-recipient survivors of childhood cancers. There are limited data on the use of TDI in assessing anthracycline-associated cardiotoxicity in children. AIM: To evaluate the role of Tissue Doppler Imaging (TDI) in assessing late-onset cardiotoxicity in survivors of paediatric cancers. MATERIALS AND METHODS: This was a single site, observational, blinded study of 11 long-term survivors of childhood cancer who had been treated with anthracyclines and 22 age-matched controls. The study group and the control group underwent conventional echo and TDI; operators were blind to study group. Conventional echo measurements were obtained. TDI was used to assess systolic and diastolic parameters at the mid-interventricular septum and lateral and medial annuli of the mitral valve; these parameters included: systolic wave (S'), early diastolic wave (E'), late diastolic wave (A'), Isovolemic Contraction Time (ICT), Isovolemic Relaxation Time (IRT) and Ejection Time (ET). Myocardial Performance Index (MPI) was also calculated. RESULTS: Conventional echo measurements were similar in both groups. Using TDI, cases had a lower mean E' velocity (9.7 ± 1.7 cm/s vs. 11.4 ± 1.3 cm/s, p=0.004) and a lower E'/A' (1.8 ± 0.5 vs. 2.2 ± 0.4, p=0.022) at the mid-interventricular septum than controls. The mean E' septum velocity in chemotherapy-recipients who also received chest radiotherapy was 8.5±0.5 cm/s in comparison to 10.2±1.7 cm/s in those that did not receive chest radiotherapy but this not achieve statistical significance. We did not find any additional associations between TDI parameters and patients' gender, age of diagnosis, length of follow-up and dose of anthracycline. CONCLUSION: In long-term survivors of childhood cancer who received anthracyclines, diastolic dysfunction can be detected earlier by using TDI before overt systolic dysfunction. Further large-scale multicenter studies are needed.

Incidental Finding of Ebstein's Anomaly in an Adolescent with an Upper Respiratory Infection: A Case Report.

Ebstein's anomaly is a rare congenital heart disorder and has a varied clinical course, with detection as late as the seventh decade. We hereby describe an 11-year-old child in whom Ebstein's anomaly was diagnosed. The most common presentation in early second decade is due to an arrhythmia; however, the present case report is about a patient who presented with acute congestive heart failure due to decompensation from an acute upper respiratory tract infection, which is a rather uncommon presentation.

Congenital Atresia of Wharton's Duct.

This is a case report of a three-month-old male who presented to clinic with a cystic lesion under the tongue. On clinical examination, a cystic lesion was observed in the, floor-of-mouth. The patient was referred to Paediatric Otorhinolaryngology service for further management. The differential diagnoses for floor-of-mouth lesions should be reviewed with primary focus on the Wharton's duct atresia and its management. It is crucial to recognize submandibular duct atresia in the primary Paediatric clinic in order to expedite management of lesion before complications arise including infection, enlargement of cyst, and feeding and breathing difficulties.

Predictors of screening for hyperlipidemia in an urban pediatric tertiary care center.

INTRODUCTION: It is unknown how the conflicting recommendations of the American Academy of Pediatrics and the US Preventive Services Task Force on pediatric hyperlipidemia affect screening. OBJECTIVES: (a) Identify clinical predictors for screening for hyperlipidemia, (b) assess the adherence to the 2008 American Academy of Pediatrics guidelines, and (c) determine the efficacy of reminder cards in increasing the adherence to the aforementioned guidelines. METHODS: Retrospective chart review in the resident, attending, and adolescent medicine clinics during a 3-month period. Reminder cards on each patient chart outlining guidelines for lipid screening for the same clinics were inserted and prospectively assessed for adherence during the following 3 months. RESULTS: Older age and higher body mass index increased likelihood (odds ratio = 1.2 and 12.7, respectively) for lipid screening. Reminder cards improved adherence in the resident clinic only (χ2 P = .016). CONCLUSIONS: Age and body mass index were the most significant predictors for lipid screening. Reminder cards modestly improved adherence among resident physicians.

Heart rate variability evaluation in the assessment and management of in-utero drug-exposed infants.

AIM: To determine whether heart rate variability parameters vary between in-utero drug-exposed infants and controls. To determine correlations between Finnegan score and heart rate variability parameters. To differentiate those drug-exposed infants who require treatment from those infants who do not. METHODS: A total of 24 jaundiced control subjects and 25 in-utero drug-exposed infants were enrolled. The Finnegan score and an electrocardiographic rhythm strip were obtained at 4-h intervals. RR intervals (time between consecutive R waves) were manually tabulated from the rhythm strip and analyzed. Time-domain heart rate variability parameters were calculated and analyzed for both groups. RESULTS: Heart rate variability parameters were cumulatively lower over 3 days in in-utero drug-exposed infants compared with controls (p < 0.05). Root mean square of differences of standard deviation of RR intervals on first day of life, and standard deviation of RR intervals, percentage of consecutive RR intervals greater than 50 ms, and root mean square of differences of standard deviation of RR intervals on the second day of life were significantly lower between in-utero drug-exposed infants and control infants. Three out of five parameters were significantly lower in in-utero drug-exposed infants pre-treatment versus post-treatment (p = 0.001, p = 0.0001, and p = 0.021, respectively). Root mean square of differences of standard deviation of RR intervals was able to differentiate in-utero drug-exposed infants requiring opiate therapy and in-utero drug-exposed infants that did not (p = 0.02). CONCLUSION: Heart rate variability analysis can contribute to the management of in-utero drug-exposed infants. Heart rate variability could be used in dose titration.

Infantile hypotonia with failure to thrive.

BACKGROUND: Pompe disease is a lysosomal glycogen storage disease (GSDII) characterized by deficiency of acid glucosidase, resulting in lysosomal glycogen accumulation in multiple tissues, with cardiac and skeletal muscles being the most seriously affected. It manifests itself as a spectrum in multiple age groups including infancy, childhood and adulthood. CASE REPORT: We present a case of infantile Pompe disease that was detected at a four month well visit in the presence of hypotonia and failure to thrive. CONCLUSIONS: Pompe disease can be diagnosed clinically by plotting growth parameters and performing developmental screening accurately. Enzyme replacement is the only available medical treatment for Pompe disease. High index of suspicion is necessary in diagnosing Pompe disease.

Nephropathy in patients after Fontan palliation.

UNLABELLED: As the effect of Fontan circulation on the kidneys has not been defined, the purpose of this study was to determine whether it is associated with nephropathy. METHODS: Patients with single ventricle physiology at least 2 years after Fontan procedure with normal cardiac function by echocardiography, history of normal renal ultrasound, and no co-morbidities known to affect the kidneys were evaluated. Patient's demographics, diagnoses, pre- and post-Fontan catheterization data, and current medications were collected. A current glomerular filtration rate (eGFR) was calculated. Morning urine samples were collected for microalbumin/creatinine ratio (MCR). RESULTS: Twenty-one subjects (M:F=13:8, ages 15.2+/-8.8 years) were studied. Primary diagnoses included hypoplastic left ventricle in 9, forms of hypoplastic right ventricle in 10, and unbalanced atrio-ventricular canal in 2 patients. Time after Fontan completion was 11.4+/-6.5 years. Current medications included aspirin (14 patients), coumadin (4), enalapril (8), lisinopril (10), digoxin (11), diuretics (5), and beta-blockers (5). Four subjects had pacemakers. All patients had a normal blood pressure and eGFR. Nine patients (43%) had a pathologic MCR (>20 microg/mg). There were no significant differences between the MCR-normal and MCR-abnormal groups in age, gender, type of single ventricle, type of the procedure, age at or time since Fontan operation. The groups differed in post-Fontan pulmonary vascular resistance (PVR) (p<0.01) and strong positive correlations were found between the MCR and pre- and post-Fontan PVR (r=0.51, p<0.05 and r=0.61, p=0.02 respectively). The MCR-normal and MCR-abnormal groups did not differ in pacemaker, digoxin, diuretics, or anticoagulant use. However, the groups were different in using ACE inhibitors with a negative correlation (r=-0.45, p=0.04) between the MCR and lisinopril-equivalent ACE inhibitor dose. Moreover, no patient receiving a lisinopril-equivalent dose greater than 0.4 mg/kg/day had pathologic microalbuminuria. In conclusion, our study demonstrates that patients with Fontan circulation have high incidence of pathologic microalbuminuria, an indicator of renal injury. The use of ACE inhibitors may be beneficial in preserving their renal function.

Morphological studies on microfilaments and their organizing center in killifish (Fundulus heteroclitus L.) melanophores.

Fish chromatophores serve as excellent study models for cytoskeleton-dependent organelle translocations because the distribution of pigmentary organelles can be observed against a time frame by microscopy. In this study the distribution of microfilaments along with microtubules in cultured melanophores of the killifish (Fundulus heteroclitus Linneaus) are examined using whole-cell transmission electron microscopy (WCTEM), fluorescence, and laser scanning confocal microscopy. Dispersing, dispersed, aggregating and aggregated states of pigment are induced by adding either caffeine (for dispersion) or epinephrine (for aggregation) to the cells in a standard culture medium. The cells that exhibited a random melanosome distribution in the standard culture media without these two reagents, served as the control. The results indicate that: (i) a structure considered to be the actin-filament organizing center (AFOC) is in close proximity to the microtubule-organizing center (MTOC); (ii) the radial layout of microfilaments remains similar over four physiological states of pigmentary response with the exception of epinephrine-aggregated pigment, in which the aggregate blocks the viewing of the AFOC and central microfilament rays, yet radial microfilaments, whether central and/or peripheral, are apparent in all physiological states of distribution; and (iii) microfilaments serve, together with microtubules, as scaffolding for melanosomes which migrate in bi-directional rows on cross-bridges, thus shedding light on the mechanisms for orderly melanosome translocations in a structural continuum.