Baylor College of Medicine

Most pediatric patients with kidney disease will be hospitalized at some point, and many of them will have multiple hospitalizations. Hospitalization can be challenging for the patient and their family based on several factors such as reason for hospitalization, prior experiences, psychological diagnoses, and typical developmental concerns in addition to logistic concerns of finances, missing work, and arranging care for the patient’s siblings. It is important for the care team to assess patient and family needs and concerns to know how to best support them during a hospitalization. There are several medical team members who help with coping and adjustment to, and support during, the hospitalization to ease the experience for patients and families, such as child life specialists, social workers, and psychologists. These providers have various areas of expertise and work closely with the patient, family, and medical team to support patients and families. Even without easy access to these services, it is important that the medical team complete basic assessments of family needs and help connect families with support. Medical providers should include patients and families in creating their care plan and use appropriate language, education, and support. Close collaboration with the patient, family, and the medical team can help the hospitalization and discharge planning progress more smoothly and lead to higher satisfaction and better overall patient-centered care.

Machine Learning (ML) techniques require novel computer programming skills along with clinical domain knowledge to produce a useful model. We demonstrate the use of a cloud-based ML tool that does not require any programming expertise to develop, validate and deploy a prognostic model for Intracerebral Haemorrhage (ICH). The data of patients admitted with Spontaneous Intracerebral haemorrhage from January 2015 to December 2019 was accessed from our prospectively maintained hospital stroke registry. 80% of the dataset was used for training, 10% for validation, and 10% for testing. Seventeen input variables were used to predict the dichotomized outcomes (Good outcome mRS 0–3/ Bad outcome mRS 4–6), using machine learning (ML) and logistic regression (LR) models. The two different approaches were evaluated using Area Under the Curve (AUC) for Receiver Operating Characteristic (ROC), Precision recall and accuracy. Our data set comprised of a cohort of 1000 patients. The data was split 8:1 for training & testing respectively. The AUC ROC of the ML model was 0.86 with an accuracy of 75.7%. With LR AUC ROC was 0.74 with an accuracy of 73.8%. Feature importance chart showed that Glasgow coma score (GCS) at presentation had the highest relative importance, followed by hematoma volume and age in both approaches. Machine learning models perform better when compared to logistic regression. Models can be developed by clinicians possessing domain expertise and no programming experience using cloud based tools. The models so developed lend themselves to be incorporated into clinical workflow.

Background Multiplexed Assays of Variant Effects (MAVEs) can test all possible single variants in a gene of interest. The resulting saturation-style functional data may help resolve variant classification disparities between populations, especially for Variants of Uncertain Significance (VUS). Methods We analyzed clinical significance classifications in 213,663 individuals of European-like genetic ancestry versus 206,975 individuals of non-European-like genetic ancestry from All of Us and the Genome Aggregation Database. Then, we incorporated clinically calibrated MAVE data into the Clinical Genome Resource’s Variant Curation Expert Panel rules to automate VUS reclassification for BRCA1, TP53, and PTEN. Results Using two orthogonal statistical approaches, we show a higher prevalence (p ≤ 5.95e − 06) of VUS in individuals of non-European-like genetic ancestry across all medical specialties assessed in all three databases. Further, in the non-European-like genetic ancestry group, higher rates of Benign or Likely Benign and variants with no clinical designation (p ≤ 2.5e − 05) were found across many medical specialties, whereas Pathogenic or Likely Pathogenic assignments were increased in individuals of European-like genetic ancestry (p ≤ 2.5e − 05). Using MAVE data, we reclassified VUS in individuals of non-European-like genetic ancestry at a significantly higher rate in comparison to reclassified VUS from European-like genetic ancestry (p = 9.1e − 03) effectively compensating for the VUS disparity. Further, essential code analysis showed equitable impact of MAVE evidence codes but inequitable impact of allele frequency (p = 7.47e − 06) and computational predictor (p = 6.92e − 05) evidence codes for individuals of non-European-like genetic ancestry. Conclusions Generation of saturation-style MAVE data should be a priority to reduce VUS disparities and produce equitable training data for future computational predictors.

The soil is the primary environmental reservoir for many parasites transmitted to humans that cause disease. Our environmental study used a multiparallel real-time quantitative polymerase chain reaction assay to detect parasite DNA in soil collected from the outdoor built environments of 34 houses in rural Yucatan, Mexico. The number of positive houses ( n , %) per parasite species was 18 (53%) for Acanthamoeba spp.; four (12%) for Blastocystis spp. and Ascaris lumbricoides ; three (9%) for Toxocara canis ; and one (3%) for Ancylostoma spp., Trichuris trichiura , Entamoeba histolytica , and Giardia intestinalis. No DNA from Necator americanus , Strongyloides stercoralis , Toxocara cati , or Cryptosporidium spp. was detected. A total of 65% of houses were positive for at least one parasite, 15% had poly-parasites, and up to six different parasites were detected in a single sample. This is one of the first reports of parasite DNA detected in soil samples from the outdoor environment in Yucatan, highlighting the presence of parasites with both zoonotic and medical significance for rural communities.

Esophagopericardial fistulas are an extremely rare structural defect that may arise from malignant or iatrogenic etiologies. This article reports the case of a patient with cardiac tamponade secondary to hydropneumopericardium from esophagopericardial fistula. Given the high morbidity and mortality of this condition, this article describes challenges in diagnosis and clinical decision-making to improve early identification and interdisciplinary management.

B-cell and plasma cell proliferations are frequently observed in nodal T follicular helper (nTfh) cell lymphomas and can present a diagnostic challenge. These proliferations can be monotypic or monoclonal and morphologically resemble lymphoma or plasmacytoma, but their clinical behavior is poorly defined. In this study, we reviewed 414 cases of nTfh lymphoma seen over the past decade at our institution. We identified 78 (19%) cases that exhibited B-cell or plasma cell proliferation detected by morphology, flow cytometry, immunohistochemistry, and/or molecular techniques. The B-cell/plasma cell proliferations occurred before (22%), concurrently with (50%), or after (28%) the diagnosis of nTfh lymphoma. We divided them into 3 categories: (1) focal or scattered B-immunoblastic proliferations recognized morphologically without a monotypic/monoclonal B-cell population (17%), (2) monotypic/monoclonal B-cell/plasma cells identified solely by flow cytometry or molecular clonality studies without morphologic confirmation (11%), and (3) unequivocal B-cell/plasma cell expansions recognized by morphologic assessment (72%). We further subdivided group 3 into proliferations associated with and possibly dependent on neoplastic Tfh cells versus those proliferations occurring in the absence of neoplastic Tfh cells and likely bona fide lymphomas. Follow-up biopsy specimens showed persistence of B-cell/plasma cell proliferations in various patient subcategories, with transformation to higher-grade B-cell proliferation or persistence without Tfh cells in some cases. In conclusion, our data support the notion that most B-cell and plasma cell proliferations associated with neoplastic Tfh clones have little impact on the clinical course of patients with nTfh lymphoma and likely do not constitute an independent B-cell lymphoma, especially those of small B cells of plasma cells. However, B-cell expansions exhibiting aggressive morphologic features may represent an independent B-cell lymphoma.

The study by Grossmann and colleagues uses single-nucleus RNA sequencing in a cohort of matched high-risk neuroblastoma primary tumor samples, obtained from the same patient at diagnosis and definitive surgery, to identify persister cells that survive induction chemotherapy. These persister cells utilize mechanisms of chemoresistance that are both tumor-intrinsic and tumor-extrinsic, are highly dependent on the original genetic profile of the tumor, and represent novel, patient-specific targets to precisely inhibit chemoresistance and disease recurrence. See related article by Grossmann et.al., p. 2387

Importance Metals are established neurotoxicants, but evidence of their association with cognitive performance at low chronic exposure levels is limited. Objective To investigate the association of urinary metal levels, individually and as a mixture, with cognitive tests and dementia diagnosis, including effect modification by apolipoprotein ε4 allele ( APOE 4). Design, Setting, and Participants The multicenter prospective cohort Multi-Ethnic Study of Atherosclerosis (MESA) was started from July 2000 to August 2002, with follow-up through 2018. A total of 6303 MESA participants were included. Data analysis was performed from October 12, 2023, to June 13, 2024. Exposure Urine samples were collected at baseline (2000-2002), and arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc levels were measured in 2020-2022. Main Outcomes and Measures Digit Symbol Coding (DSC) (n = 3819) (possible score range, 0-133), Cognitive Abilities Screening Instrument (CASI) (n = 3918) (possible score range, 0-100), and Digit Span (DS) (n = 4176) (possible score range, 0-30) cognitive tests were administered in 2010-2012; higher scores of each test indicate increasing levels of positive response. Results A total of 6303 participants were followed up for dementia diagnosis through 2018. The median age at baseline was 60 (IQR, 53-70) years, and 3303 participants (52.4%) were female. The median cognitive scores were 51 (IQR, 38-64) for DSC, 90 (IQR, 84-95) for CASI, and 15 (IQR, 12-18) for DS. There were 559 cases of dementia through the follow-up period. Inverse associations with DSC were identified: mean differences in z scores per IQR increase in metal levels were −0.03 (95% CI, −0.07 to 0.00) for arsenic, −0.05 (95% CI, −0.09 to −0.004) for cobalt, −0.05 (95% CI, −0.07 to −0.02) for copper, −0.04 (95% CI, −0.08 to −0.001) for uranium, and −0.03 (95% CI, −0.06 to −0.01) for zinc. Among 1058 APOE 4 carriers, manganese was also inversely associated with DSC. The joint mean difference of DSC comparing percentile 95th with the 25th of the 9-metal mixture was −0.30 (95% CI, −0.47 to −0.14) for APOE4 carriers and −0.10 (95% CI, −0.19 to −0.01) for noncarriers. Arsenic, cadmium, cobalt, copper, tungsten, uranium, and zinc were individually associated with dementia, with hazard ratios per IQR of metal ranging from 1.15 (95% CI, 1.03-1.29) for tungsten to 1.46 (95% CI, 1.06-2.02) for uranium. The joint hazard ratio of dementia comparing percentiles 95th with the 25th of the 9-metal mixture was 1.71 (95% CI, 1.24-3.89), with no significant difference by APOE4 status. Conclusions and Relevance In this study, participants with higher concentrations of metals in their urine, compared with those with lower concentrations, had worse performance on cognitive tests and greater likelihood of developing dementia. The findings of this multicenter multiethnic cohort study might inform screening and potential interventions for prevention of dementia based on individuals’ metal exposure levels and genetic profiles.

Importance Missed diagnosis can lead to preventable patient harm. Objective To develop and implement a portfolio of electronic triggers (e-triggers) and examine their performance for identifying missed opportunities in diagnosis (MODs) in emergency departments (EDs). Design, Setting, and Participants In this retrospective medical record review study of ED visits at 1321 Veterans Affairs health care sites, rules-based e-triggers were developed and implemented using a national electronic health record repository. These e-triggers targeted 6 high-risk presentations for MODs in treat-and-release ED visits. A high-risk stroke e-trigger was applied to treat-and-release ED visits from January 1, 2016, to December 31, 2020. A symptom-disease dyad e-trigger was applied to visits from January 1, 2018, to December 31, 2019. High-risk abdominal pain, unexpected ED return, unexpected hospital return, and test result e-triggers were applied to visits from January 1, 2019, to December 31, 2019. At least 100 randomly selected flagged records were reviewed by physician reviewers for each e-trigger. Data were analyzed between January 2024 and April 2024. Exposures Treat-and-release ED visits involving high-risk stroke, symptom-disease dyads, high-risk abdominal pain, unexpected ED return, unexpected hospital return, and abnormal test results not followed up after initial ED visit. Main Outcomes and Measures Trained physician reviewers evaluated the presence/absence of MODs at ED visits and recorded data on patient and clinician characteristics, types of diagnostic process breakdowns, and potential harm from MODs. Results The high-risk stroke e-trigger was applied to 8 792 672 treat-and-release ED visits (4 967 283 unique patients); the symptom-disease dyad e-trigger was applied to 3 692 454 visits (2 070 979 patients); and high-risk abdominal pain, unexpected ED return, unexpected hospital return, and test result e-triggers were applied to 1 845 905 visits (1 032 969 patients), overall identifying 203, 1981, 170, 116 785, 14 879, and 2090 trigger-positive records, respectively. Review of 625 randomly selected patient records (mean [SD] age, 62.5 [15.2] years; 553 [88.5%] male) showed the following MOD counts and positive predictive values (PPVs) within each category: 47 MODs (PPV, 47.0%) for stroke, 31 MODs (PPV, 25.8%) for abdominal pain, 11 MODs (PPV, 11.0%) for ED returns, 23 MODs (PPV, 23.0%) for hospital returns, 18 MODs (PPV, 18.0%) for symptom-disease dyads, and 55 MODs (PPV, 52.4%) for test results. Patients with MODs were slightly older than those without (mean [SD] age, 65.6 [14.5] vs 61.2 [15.3] years; P < .001). Reviewer agreement was favorable (range, 72%-100%). In 108 of 130 MODs (83.1%; excluding MODs related to the test result e-trigger), the most common diagnostic process breakdown involved the patient-clinician encounter. In 185 total MODs, 20 patients experienced severe harm (10.8%), and 54 patients experienced moderate harm (29.2%). Conclusions and Relevance In this retrospective medical record review study, rules-based e-triggers were useful for post hoc detection of MODs in ED visits. Interventions to target ED work system factors are urgently needed to support patient-clinician encounters and minimize harm from diagnostic errors.

Purpose of Review To summarize selected late-breaking science on cardiovascular disease (CVD) prevention presented at the 2024 European Society of Cardiology (ESC) Congress. Recent Findings Key studies from the 2024 ESC Congress highlight advances in (CVD) management. Apolipoprotein A-1 infusions reduced risk in acute myocardial infarction patients with high LDL cholesterol. Plozasiran cut triglycerides and apolipoprotein C-III levels, lowering pancreatitis risk. A 14-year study linked smoking among youth to cardiac abnormalities. Baseline hsCRP, LDL-C, and Lp(a) were strong predictors of 30-year outcomes in women. Alternative LDL-lowering strategies matched high-intensity statins in effectiveness of LDL-C lowering and reduced diabetes risk. Early combination lipid lowering therapy improved outcomes post-myocardial infarction. Nordic and Mediterranean diets were linked to lower atherosclerotic CVD risk. Summary The findings from the 2024 ESC Congress highlight significant advancements in CVD prevention, including novel lipid-lowering therapies, biomarker-based risk prediction, and lifestyle interventions. These studies underscore the importance of early and personalized treatment strategies to mitigate long-term cardiovascular risk.

Background Distinguishing serous cystadenoma, a benign pancreatic cyst, from potentially malignant mucinous pancreatic cystic lesions carries significant clinical and prognostic implications; and while endoscopic ultrasound-guided fine needle aspiration is the standard diagnostic tool, its low diagnostic yield often results in additional workup. Objective This study evaluates diagnostic yield of fine needle biopsy (FNB) on lesions suggestive of serous cystadenoma on endoscopic ultrasound. Methods Patients with microcystic EUS appearance were identified through retrospective chart review in two institutions. Prior cross sectional imaging diagnosis was also obtained. All microcystic lesions with classic “honeycomb” appearance for serous cystadenoma on EUS were targeted for FNB and their pathology evaluated. Patients were identified through database search from 2015 to 2022 and procedure information was obtained through a retrospective chart review from two large academic centers. Results Thirty-one patients with suspected serous cystadenoma who underwent EUS-FNB were included. EUS FNB was successful in obtaining diagnosis in 96.8% of patients. Serous cystadenoma was diagnosed via EUS FNB in 27 of 31 patients (87.1%). Of the remaining four patients, there was one invasive pancreatic ductal adenocarcinoma, one pancreatic neuroendocrine tumor, one intraductal papillary mucinous neoplasm, and one nondiagnostic sample. Conclusion EUS-FNB sampling for histopathology is a safe and accurate diagnostic tool for pancreatic serous cystadenoma. When microcytic lesions are found on endoscopic ultrasound, our study results suggest that fine needle biopsy for histopathology should be considered as the initial diagnostic evaluation tool given the demonstrated improved diagnostic yield for serous cystadenoma.

Purpose Postoperative analgesic requirements in adults follow circadian rhythm patterns with requirements for opioids and local anesthetics highest in the morning. Procedure time of day may also potentially affect circadian rhythm patterns with surgery at night promoting wakefulness during nighttime hours. This disruption may produce a shift in the circadian rhythm and potentially affect when postoperative opioid requirements are highest. We hypothesized that children undergoing surgery at night would have higher postoperative opioid requirements during nighttime hours secondary to a shift in the circadian rhythm with those requirements remaining higher than daytime requirements for the duration of the hospital stay. Methods A retrospective cohort was completed on all children aged 1–18 years undergoing a laparoscopic appendectomy for complicated appendicitis between January 2018 and December 2019. Outcomes were total postoperative morphine equivalents (mg/kg), including total daytime and nighttime postoperative morphine equivalents (mg/kg) in children undergoing surgery during the day and at night. Results There were 999 children who underwent a laparoscopic appendectomy for complicated appendicitis at Texas Children's Hospital from January 1, 2018 to December 31, 2019. Of these, 758 children underwent the procedure during the day and 241 children at night. The total, daytime, and nighttime median morphine equivalents (mg/kg) for children undergoing an appendectomy during the day were 0.1 (0.0–0.4), 0.0 (0.0–0.2), 0.1 (0.0–0.2), respectively. The total, daytime, and nighttime morphine equivalents (mg/kg) for children undergoing an appendectomy at night were 0.2 (0.0–0.5) ( p = −0.01), 0.1 (0.0–0.3) ( p = 0.01), and 0.1 (0.0–0.2) ( p = 0.03), respectively. All children, irrespective of the procedure time of day, required more morphine equivalents during daytime hours than during nighttime hours. Conclusions We found that procedure time of day did not impact postoperative opioid requirements in children undergoing a laparoscopic appendectomy for complicated appendicitis. Both children undergoing an appendectomy during the day or at night required more morphine equivalents during daytime hours than during nighttime hours. Surgery at night did not produce a shift in opioid requirements postoperatively from daytime hours to nighttime hours in children undergoing an appendectomy at night.

Objectives Identify existing research on impacts of transitions between electronic health record (EHR) systems on patients' healthcare experiences. Methods Scoping review. We searched MedLine, OVID, Embase, CINAHL, and PsycInfo databases for articles on patient experiences with EHR-to-EHR transitions. Results Three studies met inclusion criteria. All three used validated surveys to compare patient satisfaction with care pre- and post-transition. The surveys did not include specific questions about the EHR transition; one study focused on patient perceptions of provider computer use. Satisfaction levels initially decreased following EHR implementation, then returned to baseline between six and 15 months later in two of three studies. Factors associated with changes in observed satisfaction are unknown. Conclusions Patient experience has been given limited attention in studies of EHR-to-EHR transitions. Future research should look beyond satisfaction, and examine how an EHR-to-EHR transition can impact the quality of patients' care, including safety, effectiveness, timeliness, efficiency, and equity. Innovation To our knowledge, this is the first literature review on EHR transitions that specifically focused on patient experiences. In preparation for a transition from one EHR to another, healthcare system leaders should consider the multiple ways patients' experiences with care may be impacted and develop strategies to minimize disruptions in care.

Background For children with HIV on antiretroviral therapy (ART), transitioning to dolutegravir-containing regimens is recommended. The aim of this study was to assess whether introducing viral load testing to inform new nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) for children with HIV and viraemia alongside dolutegravir-based ART is beneficial and of good economic value. Methods We used the Cost-Effectiveness of Preventing AIDS Complications-Pediatric model to project clinical and cost implications of three strategies among a simulated cohort of South African children aged 8 years with HIV receiving abacavir–lamivudine–efavirenz: (1) continue current ART (no dolutegravir; abacavir–lamivudine–efavirenz); (2) transition all children with HIV to dolutegravir, keeping current NRTIs (dolutegravir; abacavir–lamivudine–dolutegravir); or (3) transition to dolutegravir based on viral load testing (viral load plus dolutegravir), keeping current NRTIs if virologically suppressed (abacavir–lamivudine–dolutegravir, 70% of cohort) or switching abacavir to zidovudine (zidovudine) if viraemic (zidovudine–lamivudine–dolutegravir, 30%). We assumed 50% of children who had viraemia after abacavir–lamivudine exposure had NRTI resistance; with resistance, we assumed zidovudine–lamivudine–dolutegravir was more effective than abacavir–lamivudine–dolutegravir. We designated a strategy as preferred if it was most effective and least costly or had an incremental cost-effectiveness ratio less than half the South African 2020 gross domestic product per capita. Findings Under base-case assumptions, the viral load plus dolutegravir strategy would be the most effective (projected undiscounted life expectancy of 39·72 life-years) and least costly strategy (US$24 600 per person); the no dolutegravir strategy was the least effective (34·49 life-years) and most expensive ($26 480 per person). In sensitivity analyses, the 24-week virological suppression probability and subsequent monthly virological failure risks (ie, late failure) were most influential on cost-effectiveness. Only with a high late-failure risk for zidovudine–lamivudine–dolutegravir (ie, ≥0·3% per month in the base case or >0·5% per month if abacavir also confers low virological suppression probability in the presence of NRTI resistance [65%]) would the dolutegravir strategy become preferred above the viral load plus dolutegravir strategy. Interpretation For programmes transitioning to dolutegravir-based regimens, our model predicted that doing so would be more effective and less costly than continuing current ART regimens, regardless of NRTI choice. Whether viral load testing for children with HIV is necessary to inform NRTI choice depends substantially on the comparative outcomes of abacavir and zidovudine after switching to dolutegravir-containing ART. Funding The Eunice Kennedy Shriver Institute for Child Health and Human Development, the National Institute of Allergy and Infectious Diseases, the Massachusetts General Hospital Executive Committee on Research, the Massachusetts General Hospital, and the Medical Research Council.

Two major obstacles to the widespread application of focal therapy include (1) low accuracy of risk classification models of post-focal therapy local and/or metastatic recurrence of cancer foci, (2) recognition of the multifocality of the majority of cases of prostate cancer and the likelihood of secondary (synchronous) cancer, and (3) the lack of specific and sensitive imaging modalities to accurately identify the extent or contours of intraprostatic cancer foci. In this chapter, we will address issues on cancer foci selection of cancer grade and volume, spatial location, patterns of spread, and focality according to the zone of origin—as foundations for focal therapy.

Genetic counseling is the process of helping people understand and adapt to the medical, psychological, and familial implications of genetic contributions to disease. Factors that help with the adaptation to a new genetic diagnosis include providing emotional support, information about the condition, and connections with other parents at the time of the diagnosis and throughout the diagnostic odyssey. This can be challenging if the condition is ultra-rare, as is the case for several of the RASopathies. Individuals with RASopathies are at risk for a diverse range of medical and developmental complications throughout their lifetime; thus, genetic counseling and anticipatory guidance regarding the nuances of each condition are essential in order to optimize care, management, and adaptation to the diagnosis. This chapter will explore the factors that are important when providing genetic counseling for a RASopathy before the diagnosis is made, during the diagnosis disclosure, and after the diagnosis is confirmed. This includes considerations for choosing the appropriate test and laboratory, components of pretest counseling, and variant interpretation. Recommendations for providing psychosocial support, management guidelines, and resources will also be included, in addition to discussion regarding future pregnancies, recurrence risks, and reproductive options.