Surgical Modulation of Pulmonary Artery Shear Stress: A Patient-Specific CFD Analysis of the Norwood Procedure.

PURPOSR: This study created 3D CFD models of the Norwood procedure for hypoplastic left heart syndrome (HLHS) using standard angiography and echocardiogram data to investigate the impact of shunt characteristics on pulmonary artery (PA) hemodynamics. Leveraging routine clinical data offers advantages such as availability and cost-effectiveness without subjecting patients to additional invasive procedures. METHODS: Patient-specific geometries of the intrathoracic arteries of two Norwood patients were generated from biplane cineangiograms. "Virtual surgery" was then performed to simulate the hemodynamics of alternative PA shunt configurations, including shunt type (modified Blalock-Thomas-Taussig shunt (mBTTS) vs. right ventricle-to-pulmonary artery shunt (RVPAS)), shunt diameter, and pulmonary artery anastomosis angle. Left-right pulmonary flow differential, Qp/Qs, time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) were evaluated. RESULTS: There was strong agreement between clinically measured data and CFD model output throughout the patient-specific models. Geometries with a RVPAS tended toward more balanced left-right pulmonary flow, lower Qp/Qs, and greater TAWSS and OSI than models with a mBTTS. For both shunt types, larger shunts resulted in a higher Qp/Qs and higher TAWSS, with minimal effect on OSI. Low TAWSS areas correlated with regions of low flow and changing the PA-shunt anastomosis angle to face toward low TAWSS regions increased TAWSS. CONCLUSION: Excellent correlation between clinically measured and CFD model data shows that 3D CFD models of HLHS Norwood can be developed using standard angiography and echocardiographic data. The CFD analysis also revealed consistent changes in PA TAWSS, flow differential, and OSI as a function of shunt characteristics.

Functional medicine health coaching improved elimination diet compliance and patient-reported health outcomes: Results from a randomized controlled trial.

BACKGROUND: The objective of this study was to determine whether an elimination diet with virtually provided functional medicine health coaching support would be more effective than a typical self-guided elimination diet with respect to dietary compliance and patient-reported health and quality of life. METHODS: A parallel arm, randomized controlled trial was conducted among a sample of healthcare professionals. Participants were randomized to either an elimination diet with 5 sessions of functional medicine health coaching support (intervention arm) or a self-guided elimination diet (control arm). Outcomes assessed at baseline and at the conclusion of the 10-week study included PROMIS Global Health (GH) and medical symptoms questionnaire (MSQ). Compliance with the elimination diet was assessed at the conclusion of the study. Baseline and end of study outcomes were compared within study arms via paired t tests and between study arms with unpaired t tests. Subgroup analysis of symptomatology at baseline was performed. RESULTS: 125 randomized participants (n = 64 intervention, n = 61 control) provided baseline outcomes data. There were statistically and clinically significant within-group improvements in patient-reported outcomes in both the intervention arm (PROMIS GH-physical = 4.68, PROMIS GH-mental = 3.53, MSQ = 28.9) and control arm (PROMIS GH-physical = 48.4, PROMIS GH-mental = 3.18, MSQ = 24.1). There were no between-group differences in the primary analysis (P > .1). However, participants with more symptoms at baseline had statistically and clinically significant between-group differences in PROMIS GH-mental health (3.90, P = .0038) and MSQ (12.3, P = .047) scores that favored the functional medicine health coaching arm. CONCLUSIONS: An elimination diet, whether self-guided or with functional medicine health coaching support, may improve patient-reported health outcomes among relatively healthy healthcare professionals. While studies in more diverse samples are needed, functional medicine health coaching support appears to be superior to a self-guided approach with regard to both dietary compliance and improving health outcomes among those with greater symptomatology.

Misleading Presentation: Chest Pain Masking Euglycemic Diabetic Ketoacidosis Possibly Induced by Empagliflozin.

Diabetic ketoacidosis (DKA) is a life-threatening metabolic emergency traditionally associated with Type 1 diabetes but is increasingly recognized in Type 2 diabetes, particularly with the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Euglycemic DKA, characterized by near-normal blood glucose levels, is a distinct variant that has gained attention. This case report highlights a unique presentation of euglycemic DKA in a 56-year-old female with a past medical history of Type 2 Diabetes Mellitus who presented to the emergency department with a one-week history of chest pain.

Kernicterus on the Spectrum.

Kernicterus is the potential toxic sequela of extreme neonatal hyperbilirubinemia resulting from the passage of excess free, unconjugated bilirubin across the blood-brain barrier, irreversibly and selectively damaging vulnerable target brain cells including the basal ganglia, the cerebellum, and the auditory system. Kernicterus continues to plague the modern world. Not only does it continue to be uncontrolled in developing countries with underdeveloped medical systems, and health organizations rendered ineffective by the ravages of war, but it also remains prevalent in industrialized countries. In this review, we attempt to clarify the different and overlapping nomenclature used in the past to describe this entity and aim to offer a uniform approach to defining kernicterus spectrum disorder. We also discuss the different spectrum subtypes including motor-predominant kernicterus, auditory neural sensory dysfunction, subtle kernicterus, and kernicterus plus. In addition to reviewing several genetic factors that increase the risk of developing kernicterus, we also present some exciting potential therapeutic approaches.

Patient well-being and the clinical and economic burdens associated with obesity in the United States.

Obesity is a serious, progressive, chronic disease that is associated with a spectrum of complications and poor outcomes (eg, premature death, diminished quality of life) and is a risk factor for several other diseases. Obesity increases the risk of developing type 2 diabetes, cardiovascular disease, and certain cancers. More recently, obesity was recognized as a risk factor for poor outcomes in patients with COVID-19. When experienced concurrently with a serious disease, obesity may increase the risk of negative health outcomes. Furthermore, individuals with obesity are more likely to experience social stigma and discrimination at work and in educational and health care settings; these may impact mental and physical health and contribute to increased adiposity. In the United States, the economic burden of obesity is immense-according to estimates, hundreds of billions of dollars are spent annually on direct medical needs and lost productivity associated with obesity. More severe classes of obesity greatly impact both the health of individuals and health care expenditures. As obesity becomes more prevalent, policy makers, health care professionals, and payers must consider its clinical, social, and economic implications.

Managed care considerations of weight management interventions for obesity.

The growing prevalence of obesity in the United States has presented an opportunity to increase knowledge about optimal treatment approaches based on a better understanding of patient and provider biases, health care coverage and practices, and social determinants of health. Guideline-recommended obesity treatment begins with lifestyle intervention, and weight management may be enhanced by metabolic and bariatric surgery or anti-obesity medication (AOM) use. However, patient and provider perceptions surrounding obesity and different treatment modalities may present barriers to discussion and uptake of these interventions. Furthermore, it is uncommon for all effective obesity treatments (particularly AOMs) to be covered by insurance. Limited patient access to these treatments carries the potential for negative health consequences and higher health care costs. For these reasons, managed care decision makers are encouraged to improve access to effective obesity treatments, including coverage of AOMs such as semaglutide 2.4 mg.

Mechanical extraction of chronic venous thrombus using a novel device: a report of two cases.

In deep vein thrombosis (DVT), the structure and composition of the venous thrombus can change rapidly over time. Studies have shown mixed results with anticoagulant and thrombolytic therapies, and the issue will be exacerbated in the case of chronic DVT (defined as thrombus still present after ≥4 weeks of failed treatment after a DVT diagnosis), with no well-accepted interventions. In the present report, we have described two patients in whom mechanical thrombectomy with a novel device was used to remove extensive, chronic thrombus. At follow-up, both patients showed improved blood flow and patency with resolution of their edema and pain. Because thrombus can often be more chronic than expected from a patient's medical history alone, mechanical intervention as the first approach might be warranted.

Breastfeeding challenges and support in a high initiation population.

BACKGROUND: The breastfeeding initiation rate in Israel is approximately 90%, yet exclusive breastfeeding drops sharply in the early postnatal period. The study objective was to assess early postpartum professional breastfeeding support, its association with breastfeeding success and identification of risk factors for early breastfeeding discontinuation. METHODS: As part of a post-discharge newborn follow-up study, a convenience sample of 868 mothers attending Maternal and Child Health Centers (MCHCs) up to three months post-partum were interviewed using a 26-item questionnaire. Breastfeeding-related questions covered demographic variables, pregnancy and birth details; breastfeeding duration, lactation support in hospital and post-discharge; and problems experienced. RESULTS: Most mothers, 797 (91.8%), initiated breastfeeding in hospital. All women who initiated breastfeeding in the hospital reported exclusive breastfeeding; by two weeks postpartum, 70 women (13.2%) were supplementing with formula (partial breastfeeding). Kaplan-Meier Survival Analysis revealed an estimated mean duration of exclusive breastfeeding in the sample population of 66.8 ± 1.5 days. This duration was shorter for women with preterm births, low birthweight infants (LBW), cesarean births, and hospitalizations in neonatal intensive care units (NICU). A total of 472 (59.3%) breastfeeding mothers reported receiving in-hospital guidance. Of these, 290 (61.3%) were observed breastfeeding. Of all women who initiated breastfeeding, 280 (35.1%) attended MCHC follow-up within 72 h of hospital discharge. A higher proportion of women experiencing breastfeeding difficulties attended an MCHC within 72 h (131/297, 44.1%) compared to women not experiencing difficulties (148/499, 29.7%). The most frequently reported problems were mechanical (55.2%) or milk supply concerns (18.5%). First-time mothers were more likely to report problems, as were Jewish (vs Arab) mothers. CONCLUSIONS: Even in a population with high initiation rates of breastfeeding, breastfeeding duration, both exclusive and partial, is less than recommended. As much of this drop-off occurs during maternity leave, it is likely related to breastfeeding challenges other than employment. Breastfeeding support needs of women are currently not adequately met; staffing and time for both in-hospital and community-based counseling needs to be funded as well as mandated. Counseling hours should be tailored to assure adequate coverage of high-risk groups such as women after cesarean delivery and newborns requiring intensive care.

89Zr-panitumumab Combined With 18F-FDG PET Improves Detection and Staging of Head and Neck Squamous Cell Carcinoma.

PURPOSE: Determine the safety and specificity of a tumor-targeted radiotracer (89Zr-pan) in combination with 18F-FDG PET/CT to improve diagnostic accuracy in head and neck squamous cell carcinoma (HNSCC). EXPERIMENTAL DESIGN: Adult patients with biopsy-proven HNSCC scheduled for standard-of-care surgery were enrolled in a clinical trial and underwent systemic administration of 89Zirconium-panitumumab and panitumumab-IRDye800 followed by preoperative 89Zr-pan PET/CT and intraoperative fluorescence imaging. The sensitivity, specificity, and AUC were evaluated. RESULTS: A total of fourteen patients were enrolled and completed the study. Four patients (28.5%) had areas of high 18F-FDG uptake outside the head and neck region with maximum standardized uptake values (SUVmax) greater than 2.0 that were not detected on 89Zr-pan PET/CT. These four patients with incidental findings underwent further workup and had no evidence of cancer on biopsy or clinical follow-up. Forty-eight lesions (primary tumor, LNs, incidental findings) with SUVmax ranging 2.0-23.6 were visualized on 18F-FDG PET/CT; 34 lesions on 89Zr-pan PET/CT with SUVmax ranging 0.9-10.5. The combined ability of 18F-FDG PET/CT and 89Zr-pan PET/CT to detect HNSCC in the whole body was improved with higher specificity of 96.3% [confidence interval (CI), 89.2%-100%] compared to 18F-FDG PET/CT alone with specificity of 74.1% (CI, 74.1%-90.6%). One possibly related grade 1 adverse event of prolonged QTc (460 ms) was reported but resolved in follow-up. CONCLUSIONS: 89Zr-pan PET/CT imaging is safe and may be valuable in discriminating incidental findings identified on 18F-FDG PET/CT from true positive lesions and in localizing metastatic LNs.

Aldehyde dehydrogenase 3A1 deficiency leads to mitochondrial dysfunction and impacts salivary gland stem cell phenotype.

Adult salivary stem/progenitor cells (SSPC) have an intrinsic property to self-renew in order to maintain tissue architecture and homeostasis. Adult salivary glands have been documented to harbor SSPC, which have been shown to play a vital role in the regeneration of the glandular structures postradiation damage. We have previously demonstrated that activation of aldehyde dehydrogenase 3A1 (ALDH3A1) after radiation reduced aldehyde accumulation in SSPC, leading to less apoptosis and improved salivary function. We subsequently found that sustained pharmacological ALDH3A1 activation is critical to enhance regeneration of murine submandibular gland after radiation damage. Further investigation shows that ALDH3A1 function is crucial for SSPC self-renewal and survival even in the absence of radiation stress. Salivary glands from Aldh3a1 -/- mice have fewer acinar structures than wildtype mice. ALDH3A1 deletion or pharmacological inhibition in SSPC leads to a decrease in mitochondrial DNA copy number, lower expression of mitochondrial specific genes and proteins, structural abnormalities, lower membrane potential, and reduced cellular respiration. Loss or inhibition of ALDH3A1 also elevates ROS levels, depletes glutathione pool, and accumulates ALDH3A1 substrate 4-hydroxynonenal (4-HNE, a lipid peroxidation product), leading to decreased survival of murine SSPC that can be rescued by treatment with 4-HNE specific carbonyl scavengers. Our data indicate that ALDH3A1 activity protects mitochondrial function and is important for the regeneration activity of SSPC. This knowledge will help to guide our translational strategy of applying ALDH3A1 activators in the clinic to prevent radiation-related hyposalivation in head and neck cancer patients.

Glacier fluctuations in the northern Patagonian Andes (44°S) imply wind-modulated interhemispheric in-phase climate shifts during Termination 1.

The Last Glacial Termination (T1) featured major changes in global circulation systems that led to a shift from glacial to interglacial climate. While polar ice cores attest to an antiphased thermal pattern at millennial timescales, recent well-dated moraine records from both hemispheres suggest in-phase fluctuations in glaciers through T1, which is inconsistent with the bipolar see-saw paradigm. Here, we present a glacier chronology based on 30 new 10Be surface exposure ages from well-preserved moraines in the Lago Palena/General Vintter basin in northern Patagonia (~ 44°S). We find that the main glacier lobe underwent profound retreat after 19.7 ± 0.7 ka. This recessional trend led to the individualization of the Cerro Riñón glacier by ~ 16.3 ka, which underwent minor readvances at 15.9 ± 0.5 ka during Heinrich Stadial 1, during the Antarctic Cold Reversal with successive maxima at 13.5 ± 0.4, 13.1 ± 0.4, and 13.1 ± 0.5 ka, and a minor culmination at 12.5 ± 0.4 ka during Younger Dryas time. We conclude that fluctuations of Patagonian glaciers during T1 were controlled primarily by climate anomalies brought by shifts in the Southern Westerly Winds (SWW) locus. We posit that the global covariation of mountain glaciers during T1 was linked to variations in atmospheric CO2 (atmCO2) promoted by the interplay of the SWW-Southern Ocean system at millennial timescales.

Characterization of hemodynamics in anomalous aortic origin of coronary arteries using patient-specific modeling.

The anomalous aortic origin of coronary arteries (AAOCA) is a congenital disease that can lead to sudden cardiac death (SCD) during strenuous physical activity. Despite AAOCA being the second leading cause of SCD among young athletes, the mechanism behind sudden cardiac death remains mostly unknown. Computational fluid dynamics provides a powerful tool for studying how pathologic anatomy can affect different hemodynamic states. The present study investigates the effect of AAOCA on patient hemodynamics. We performed patient-specific hemodynamic simulations of interarterial AAOCA at baseline and in the exercise state using our massively parallel flow solver. Additionally, we investigate how surgical correction via coronary unroofing impacts patient blood flow. Results show that patient-specific AAOCA models exhibited higher interarterial time-averaged wall shear stress (TAWSS) values compared to the control patients. The oscillatory shear index had no impact on AAOCA. Finally, the coronary unroofing procedure normalized the elevated TAWSS by decreasing TAWSS in the postoperative patient. The present study provides a proof of concept for the potential hemodynamic factors underlying coronary ischemia in AAOCA during exercise state.

Multisite evaluation of fire ant venom immunotherapy safety and efficacy.

Background: Imported fire ant (IFA) venom immunotherapy (VIT) is the only disease-modifying treatment reported to be effective at decreasing the risk of systemic reactions (SRs) to IFA stings. Objective: Our aims were to determine the baseline rates of IFA sensitization in subjects, describe IFA VIT prescribing patterns across the military health system (MHS), and retrospectively evaluate the safety and efficacy of IFA VIT. Methods: We prospectively compared IFA sensitization in participants with and without an SR to flying Hymenoptera venom. Separately, IFA VIT prescription records were extracted from a centralized repository, and rates were described across the MHS. Additionally, we retrospectively reviewed the clinical course of patients being treated with IFA VIT at 11 military treatment facilities. Results: The in vitro IFA sensitization rates in our prospective cohort ranged from 19.1% to 24.1%. Sensitization rates did not differ statistically between the subjects with or without an SR to flying Hymenoptera venom. We found that 60.9% of all MHS IFA VIT prescriptions (491 of 806) were from the 11 facilities in this study. We retrospectively identified 137 subjects actively undergoing IFA VIT. Among the subjects actively undergoing IFA VIT, 28 reported an SR to IFA venom and repeat stings by IFAs after reaching VIT maintenance, and 85.7% (24 of 28) of the subjects noted symptoms no worse than a large swelling reaction after a repeat IFA sting. Notably, only 2.9% of the subjects (4 of 137) had an SR due to VIT. Conclusion: This study's results align with those of prior IFA sensitization reports. A substantial proportion of patients undergoing IFA VIT experienced protection against anaphylaxis with reexposure, with relatively few adverse events.

Seroepidemiologic Investigation of a COVID-19 Outbreak Aboard a U.S. Navy Ship.

The crew of USS Kidd experienced a COVID-19 outbreak identified in April 2020. This is the earliest documented COVID-19 study with RT-PCR, serology, and pre-exposure test data on the entirety of the exposed population (n=333). Case definitions included 121 confirmed (36.3% of crewmembers) and 18 probable (5.4% of crewmembers) based on laboratory diagnostic test results. At the time of testing positive, 62 (44.6%) cases reported no symptoms. Hispanic ethnicity (AOR: 2.71, CI: 1.40-5.25) and non-smoker status (AOR: 2.28, CI: 1.26-4.12) were identified as statistically significant risk factors. This study highlights the value of rapid, onboard diagnostic testing to quickly identify an outbreak and enumerate cases, as well as the serological testing to flag potential cases missed with standard viral case identification methodologies.

Hyperbilirubinemia in the Term Infant: Re-evaluating What We Think We Know.

This article attempts to highlight contemporary issues relating to term neonatal hyperbilirubinemia and to focus attention on controversial issues and concepts with the potential to effect change in clinical approach. On the one hand, the focus is bilirubin neurotoxicity, which is now known to encompass a wide, diverse spectrum of features. The various aspects of this spectrum are outlined and defined. On the other hand, bilirubin also possesses antioxidant properties. As such, mild hyperbilirubinemia is suggested as actually offering the neonate some protective advantage.

Landscape of innate lymphoid cells in human head and neck cancer reveals divergent NK cell states in the tumor microenvironment.

Natural killer (NK) cells comprise one subset of the innate lymphoid cell (ILC) family. Despite reported antitumor functions of NK cells, their tangible contribution to tumor control in humans remains controversial. This is due to incomplete understanding of the NK cell states within the tumor microenvironment (TME). Here, we demonstrate that peripheral circulating NK cells differentiate down two divergent pathways within the TME, resulting in different end states. One resembles intraepithelial ILC1s (ieILC1) and possesses potent in vivo antitumor activity. The other expresses genes associated with immune hyporesponsiveness and has poor antitumor functional capacity. Interleukin-15 (IL-15) and direct contact between the tumor cells and NK cells are required for the differentiation into CD49a+CD103+ cells, resembling ieILC1s. These data explain the similarity between ieILC1s and tissue-resident NK cells, provide insight into the origin of ieILC1s, and identify the ieILC1-like cell state within the TME to be the NK cell phenotype with the greatest antitumor activity. Because the proportions of the different ILC states vary between tumors, these findings provide a resource for the clinical study of innate immune responses against tumors and the design of novel therapy.