Like Father like Daughter: Surgical Redo Thoracoabdominal Aneurysm Repairs in a Family With Loeys-Dietz Syndrome.

Loeys Dietz Syndrome (LDS) is an autosomal dominant connective tissue disorder resulting from a mutation in the transforming growth factor beta receptor (TGFBR) family of genes. It is commonly associated with the development of aortic aneurysms and dissections. We report the successful open surgical management of thoracoabdominal aneurysms in a father and daughter with Loeys-Dietz Syndrome after failed endovascular repair. The daughter required stent graft explantation, while the stent graft remained in the father. These cases highlight the importance of early genetic testing of both patients and first-degree family members in those with a strong history of aortic disease, even when there is a lack of typical connective tissue disorder associated physical exam findings and open surgical index operations.

Wearable magnetoencephalography in a lightly shielded environment.

Wearable magnetoencephalography based on optically pumped magnetometers (OPM-MEG) offers non-invasive and high-fidelity measurement of human brain electrophysiology. The flexibility of OPM-MEG also means it can be deployed in participants of all ages and permits scanning during movement. However, the magnetic fields generated by neuronal currents - which form the basis of the OPM-MEG signal - are much smaller than environmental fields, and this means measurements are highly sensitive to interference. Further, OPMs have a low dynamic range, and should be operated in near-zero background field. Scanners must therefore be housed in specialised magnetically shielded rooms (MSRs), formed from multiple layers of shielding material. The MSR is a critical component, and current OPM-optimised shields are large (>3 m in height), heavy (>10,000 kg) and expensive (with up to 5 layers of material). This restricts the uptake of OPM-MEG technology. Here, we show that the application of the Maxwell filtering techniques signal space separation (SSS) and its spatiotemporal extension (tSSS) to OPM-MEG data can isolate small signals of interest measured in the presence of large interference. We compare phantom recordings and MEG data from a participant performing a motor task in a state-of-the-art 5-layer MSR, to similar data collected in a lightly shielded room: application of tSSS to data recorded in the lightly shielded room allowed accurate localisation of a dipole source in the phantom and neuronal sources in the brain. Our results point to future deployment of OPM-MEG in lighter, cheaper and easier-to-site MSRs which could catalyse widespread adoption of the technology.

Superior Vena Cava Syndrome Masquerading as Angioedema: A Chemotherapy Port Complication.

Superior vena cava (SVC) syndrome is a constellation of symptoms that occur secondary to external compression of the SVC, most commonly by a mediastinal malignancy. With the increased use of implanted cardiac devices and indwelling central venous catheters, SVC syndrome from a benign cause has become quite common. This report follows a 62-year-old female who was initially admitted to the critical care unit for treatment of angioedema without a history of malignancy but was found to have a surgically placed port used to treat her rheumatoid arthritis. Despite treatment of what was presumed to be angioedema, her symptoms failed to resolve. Imaging of the thorax revealed a venous thrombosis in the previously placed port. The port was subsequently removed, and the patient's symptoms hastily resolved. This case report underscores the importance of obtaining a thorough history, maintaining a broad differential diagnosis, and revising the differential when the patient's symptoms fail to improve.

Oncology stewardship practice in the United States: A Hematology/Oncology Pharmacy Association national survey.

INTRODUCTION: The treatment of cancer is associated with high risk for toxicity and high cost. Strategies to enhance the value, quality, and safety of cancer care are often managed independently of one another. Oncology stewardship is a potential framework to unify these efforts and enhance outcomes. This landscape survey establishes baseline information on oncology stewardship in the United States. METHODS: The Hematology/Oncology Pharmacy Association (HOPA) distributed a 38-item survey composed of demographic, institutional, clinical decision-making, support staff, metrics, and technology sections to 675 HOPA members between 9 September 2022 and 9 October 2022. RESULTS: Most organizations (78%) have adopted general pharmacy stewardship practices; however, only 31% reported having established a formalized oncology stewardship team. More than 70% of respondents reported implementation of biosimilars, formulary management, and dose rounding as oncology stewardship initiatives in both inpatient and outpatient settings. Frequently cited barriers to oncology stewardship included lack of clinical pharmacist availability (74%), lack of oncology stewardship training (62%), lack of physician/provider buy-in (32%), and lack of cost-saving metrics (33%). Only 6.6% of survey respondents reported their organization had defined "value in oncology." Lack of a formalized stewardship program was most often cited (77%) as the rationale for not defining value. CONCLUSIONS: Less than one-third of respondents have established oncology stewardship programs; however, most are providing oncology stewardship practices. This manuscript serves as a call to action for stakeholders to work together to formalize oncology stewardship programs that optimize value, quality, and safety for patients with cancer.

Outcomes of Deep Hypothermic Circulatory Arrest for Descending and Thoracoabdominal Aneurysm Repair.

BACKGROUND: Deep hypothermic circulatory arrest (DHCA) in patients undergoing descending thoracic (DTAA) or thoracoabdominal aortic aneurysm (TAAA) repair is associated with increased morbidity and mortality. We present our outcomes after open DTAA and TAAA repair with and without DHCA. METHODS: From 1999 to 2022, 81 (38.8%) patients undergoing DTAA or TAAA repair required DHCA because proximal cross-clamping was not feasible or aneurysmal pathology extended into the arch and 128 (61.2%) patients required only distal bypass. Because of intrinsic pathological differences in patients requiring DHCA, confidence intervals (CIs) were used to compare groups in lieu of formal hypothesis tests. RESULTS: DHCA patients had more chronic dissections (64.2% vs. 43.8%, 95% CI for difference: 6-35%) and higher body mass indices (29.5 ± 6.8 vs. 27.2 ± 6.6, CI: 26-421%). More non-DHCA patients had medial degeneration (9.9% vs. 31.3%, CI: -33 to -7%). There were 10 (12.4%) in-hospital deaths for the DHCA and 10 (7.8%) for the non-DHCA group (CI: -5 to 14%). Survival at 10 years was 52.6% (CI: 42.1-65.7%) for the non-DHCA group and 48.3% (CI: 40.3-57.9%) for the DHCA group. The only meaningful differences in postoperative outcomes were intensive care unit (5.5 days vs. 6 days, CI: 12-410%) and hospital stay (19 days vs. 12 days, CI: 74-470%), which were longer in the DHCA group. CONCLUSIONS: Despite longer intensive care unit and hospital length of stays, selective use of DHCA is safe and effective with comparable morbidity and mortality to non-DHCA in open DTAA and TAAA repair.

Bilateral antegrade cerebral perfusion during hypothermic circulatory arrest before sternal reentry for aortic pseudoaneurysm repair.

Sternal reentry for repair of aortic pseudoaneurysms poses a unique technical challenge to prevent exsanguination. Initiation of peripheral cardiopulmonary bypass and deep hypothermic circulatory arrest prior to reentry are the cornerstones of a successful surgical approach. Adjunctive bilateral antegrade cerebral perfusion increases safe arrest time and reduces neurologic morbidity. Herein, we describe our safe reentry technique for aortic pseudoaneurysm repair in two patients.

Reducing Cancer Drug Cost: 3-Year Analysis of Automated Dose Rounding in Electronic Health Records.

PURPOSE: Globally, cancer drug expenditure exceeds $185 in US dollars (USD) billion, with the United States contributing $75 (USD) billion. Many cancer drug doses are calculated on the basis of body weight or body surface area, which often results in leftover drug in partially used single-dose vials (SDVs). The cost of wasted drug is a huge financial burden on the US health care system. We evaluated the cost savings resulting from the reduction of SDV wastage, achieved through the implementation of automated dose rounding rules in electronic health records (EHRs). METHODS: Mayo Clinic implemented automated dose rounding rules within the EHR. These rules were designed to round calculated doses to the nearest SDV if the vial size closely matched the original calculated dose, within a 10% threshold. We assessed doses administered between January 2019 and December 2021, and computed cost-savings, waste reduction, and cost of waste for chemotherapy drugs. RESULTS: In 3 years, 36.1% of doses were rounded down, 35.8% were rounded up, and 28.1% were exact doses. By rounding doses down to a vial size, we achieved cost-savings of $39.75 (USD) million and prevented 62,065 SDV of cancer drugs from going to waste. By rounding doses up, we avoided wasting $9.95 (USD) million worth of drugs. However, there were still instances where the rounding fell outside of the 10%, resulting in wasted drugs worth $25 (USD) million. CONCLUSION: The substantial burden imposed on patients and the US health care system because of cancer drug wastage is of significant concern. Although the automated dose rounding system represents a partial solution for this issue, a comprehensive approach involves the imperative development of policy and legislative solutions to effectively mitigate the challenges associated with cancer drug waste.

Non-invasive ventral cervical magnetoneurography as a proxy of in vivo lipopolysaccharide-induced inflammation.

Maintenance of autonomic homeostasis is continuously calibrated by sensory fibers of the vagus nerve and sympathetic chain that convey compound action potentials (CAPs) to the central nervous system. Lipopolysaccharide (LPS) intravenous challenge reliably elicits a robust inflammatory response that can resemble systemic inflammation and acute endotoxemia. Here, we administered LPS intravenously in nine healthy subjects while recording ventral cervical magnetoneurography (vcMNG)-derived CAPs at the rostral Right Nodose Ganglion (RNG) and the caudal Right Carotid Artery (RCA) with optically pumped magnetometers (OPM). We observed vcMNG RNG and RCA neural firing rates that tracked changes in TNF-α levels in the systemic circulation. Further, endotype subgroups based on high and low IL-6 responders segregate RNG CAP frequency (at 30-120 min) and based on high and low IL-10 response discriminate RCA CAP frequency (at 0-30 min). These vcMNG tools may enhance understanding and management of the neuroimmune axis that can guide personalized treatment based on an individual's distinct endophenotype.

A Systematic Review Supporting the Endocrine Society Clinical Practice Guidelines on Vitamin D.

CONTEXT: Low vitamin D status is common and is associated with various common medical conditions. OBJECTIVE: To support the development of the Endocrine Society's Clinical Practice Guideline on Vitamin D for the Prevention of Disease. METHODS: We searched multiple databases for studies that addressed 14 clinical questions prioritized by the guideline panel. Of the 14 questions, 10 clinical questions assessed the effect of vitamin D vs no vitamin D in the general population throughout the lifespan, during pregnancy, and in adults with prediabetes; 1 question assessed dosing; and 3 questions addressed screening with serum 25-hydroxyvitamin D (25[OH]D). The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess certainty of evidence. RESULTS: Electronic searches yielded 37 007 citations, from which we included 151 studies. In children and adolescents, low-certainty evidence suggested reduction in respiratory tract infections with empiric vitamin D. There was no significant effect on select outcomes in healthy adults aged 19 to 74 years with variable certainty of evidence. There was a very small reduction in mortality among adults older than 75 years with high certainty of evidence. In pregnant women, low-certainty evidence suggested possible benefit on various maternal, fetal, and neonatal outcomes. In adults with prediabetes, moderate certainty of evidence suggested reduction in the rate of progression to diabetes. Administration of high-dose intermittent vitamin D may increase falls, compared to lower-dose daily dosing. We did not identify trials on the benefits and harms of screening with serum 25(OH)D. CONCLUSION: The evidence summarized in this systematic review addresses the benefits and harms of vitamin D for the prevention of disease. The guideline panel considered additional information about individuals' and providers' values and preferences and other important decisional and contextual factors to develop clinical recommendations.

Tracking the neurodevelopmental trajectory of beta band oscillations with optically pumped magnetometer-based magnetoencephalography.

Neural oscillations mediate the coordination of activity within and between brain networks, supporting cognition and behaviour. How these processes develop throughout childhood is not only an important neuroscientific question but could also shed light on the mechanisms underlying neurological and psychiatric disorders. However, measuring the neurodevelopmental trajectory of oscillations has been hampered by confounds from instrumentation. In this paper, we investigate the suitability of a disruptive new imaging platform - optically pumped magnetometer-based magnetoencephalography (OPM-MEG) - to study oscillations during brain development. We show how a unique 192-channel OPM-MEG device, which is adaptable to head size and robust to participant movement, can be used to collect high-fidelity electrophysiological data in individuals aged between 2 and 34 years. Data were collected during a somatosensory task, and we measured both stimulus-induced modulation of beta oscillations in sensory cortex, and whole-brain connectivity, showing that both modulate significantly with age. Moreover, we show that pan-spectral bursts of electrophysiological activity drive task-induced beta modulation, and that their probability of occurrence and spectral content change with age. Our results offer new insights into the developmental trajectory of beta oscillations and provide clear evidence that OPM-MEG is an ideal platform for studying electrophysiology in neurodevelopment.

A Novel, Robust, and Portable Platform for Magnetoencephalography using Optically Pumped Magnetometers.

Magnetoencephalography (MEG) measures brain function via assessment of magnetic fields generated by neural currents. Conventional MEG uses superconducting sensors, which place significant limitations on performance, practicality, and deployment; however, the field has been revolutionised in recent years by the introduction of optically-pumped-magnetometers (OPMs). OPMs enable measurement of the MEG signal without cryogenics, and consequently the conception of 'OPM-MEG' systems which ostensibly allow increased sensitivity and resolution, lifespan compliance, free subject movement, and lower cost. However, OPM-MEG remains in its infancy with limitations on both sensor and system design. Here, we report a new OPM-MEG design with miniaturised and integrated electronic control, a high level of portability, and improved sensor dynamic range (arguably the biggest limitation of existing instrumentation). We show that this system produces equivalent measures when compared to an established instrument; specifically, when measuring task-induced beta-band, gamma-band and evoked neuro-electrical responses, source localisations from the two systems were highly comparable and temporal correlation was >0.7 at the individual level and >0.9 for groups. Using an electromagnetic phantom, we demonstrate improved dynamic range by running the system in background fields up to 8 nT. We show that the system is effective in gathering data during free movement (including a sitting-to-standing paradigm) and that it is compatible with simultaneous electroencephalography (EEG - the clinical standard). Finally, we demonstrate portability by moving the system between two laboratories. Overall, our new system is shown to be a significant step forward for OPM-MEG technology and offers an attractive platform for next generation functional medical imaging.

Three-Dimensional Epitaxy of Low-Defect 3C-SiC on a Geometrically Modified Silicon Substrate.

We demonstrate the growth of 3C-SiC with reduced planar defects on a micro-scale compliant substrate. Heteroepitaxial growth of 3C-SiC on trenches with a width and separation of 2 µm, etched into a Si(001) substrate, is found to suppress defect propagation through the epilayer. Stacking faults and other planar defects are channeled away from the center of the patterned structures, which are rounded through the use of H2 annealing at 1100 °C. Void formation between the columns of 3C-SiC growth acts as a termination point for defects, and coalescence of these columns into a continuous epilayer is promoted through the addition of HCl in the growth phase. The process of fabricating these compliant substrates utilizes standard processing techniques found within the semiconductor industry and is independent of the substrate orientation and offcut.

Structure-Based Optimization of Selective and Brain Penetrant CK1δ Inhibitors for the Treatment of Circadian Disruptions.

Neuropsychiatric disorders such as major depressive disorders and schizophrenia are often associated with disruptions to the normal 24 h sleep wake cycle. Casein kinase 1 (CK1δ) is an integral part of the molecular machinery that regulates circadian rhythms. Starting from a cluster of bicyclic pyrazoles identified from a virtual screening effort, we utilized structure-based drug design to identify and reinforce a unique "hinge-flip" binding mode that provides a high degree of selectivity for CK1δ versus the kinome. Pharmacokinetics, brain exposure, and target engagement as measured by ex vivo autoradiography are described for advanced analogs.

A Design-Conversed Strategy Establishes the Performance Safe Space for Doxorubicin Nanosimilars.

Nanomedicines exhibit multifaceted performances, yet their biopharmaceutics remain poorly understood and present several challenges in the translation from preclinical to clinical research. To address this issue and promote the production of high-quality nanomedicines, a systematic screening of the design space and in vivo performance is necessary. Establishing formulation performance specifications early on enables an informed selection of candidates and promotes the development of nanosimilars. The deconvolution of the pharmacokinetics enables the identification of key characteristics that influence their performances and disposition. Using an in vitro-in vivo rank-order relationship for doxorubicin nanoformulations, we defined in vitro release specifications for Doxil/Caelyx-like follow-on products. Additionally, our model predictions were used to establish the bioequivalence of Lipodox, a nanosimilar of Doxil/Caelyx. Furthermore, a virtual safe space was established, providing crucial insights into expected disposition kinetics and informing formulation development. By addressing bottlenecks in biopharmaceutics and formulation screening, our research advances the translation of nanomedicine from bench to bedside.

The neurodevelopmental trajectory of beta band oscillations: an OPM-MEG study.

Neural oscillations mediate the coordination of activity within and between brain networks, supporting cognition and behaviour. How these processes develop throughout childhood is not only an important neuroscientific question but could also shed light on the mechanisms underlying neurological and psychiatric disorders. However, measuring the neurodevelopmental trajectory of oscillations has been hampered by confounds from instrumentation. In this paper, we investigate the suitability of a disruptive new imaging platform - Optically Pumped Magnetometer-based magnetoencephalography (OPM-MEG) - to study oscillations during brain development. We show how a unique 192-channel OPM-MEG device, which is adaptable to head size and robust to participant movement, can be used to collect high-fidelity electrophysiological data in individuals aged between 2 and 34 years. Data were collected during a somatosensory task, and we measured both stimulus-induced modulation of beta oscillations in sensory cortex, and whole-brain connectivity, showing that both modulate significantly with age. Moreover, we show that pan-spectral bursts of electrophysiological activity drive task-induced beta modulation, and that their probability of occurrence and spectral content change with age. Our results offer new insights into the developmental trajectory of beta oscillations and provide clear evidence that OPM-MEG is an ideal platform for studying electrophysiology in neurodevelopment.

The Royal College of Ophthalmologists' National Ophthalmology Database Study of Cataract Surgery: Report 13, monitoring post-cataract surgery endophthalmitis rates-the rule of X.

BACKGROUND: Cataract surgical safety has improved over recent decades, with endophthalmitis rates before 2006 typically 0.13-0.15% compared with the most recent UK national estimate of 0.02%. There remains, however, substantial variation in reported rates from different centres. Due to the low event rate, this disparity may not be noticed and opportunities to improve therefore be missed. We propose a method of monitoring post-cataract endophthalmitis rates that would help centres with higher rates identify this. METHODS: A statistical tool, available to download or use online, permits comparison of local endophthalmitis rate with the estimated UK rate of 0.02%. Centres are encouraged to maintain a register of endophthalmitis cases, and when the number reaches a threshold (X cases), either in a certain time period or in a fixed number of procedures, then the centre can consider itself as an outlier and trigger local investigations to improve infection control. RESULTS: Example outputs are offered, such as for a unit doing 5000 cataracts annually, a value of X is suggested such that the third case of endophthalmitis (X = 3) in a 12-month period would give 85% confidence, the fourth case 90% confidence and the fifth case 95% confidence that the true endophthalmitis rate for that unit was higher than the national average. CONCLUSIONS: This statistical tool provides a basis for units to set a threshold number of cases of endophthalmitis within a given period that would trigger local processes, thus helping inform local monitoring processes for this rare but potentially catastrophic complication of cataract surgery.

Upper Hemisternotomy Versus Full Sternotomy for Replacement of the Supracoronary Ascending Aorta and Aortic Valve.

OBJECTIVE: Upper hemisternotomy (UHS) for supracoronary ascending aorta replacement (scAAR) with concomitant aortic valve replacement (AVR) results in less trauma and potentially faster convalescence compared with full sternotomy (FS). Direct head-to-head studies are lacking. We compared a group of UHS patients with a matched group of FS patients undergoing scAAR and AVR. METHODS: There were 198 patients who underwent scAAR and AVR procedures by a single surgeon between 1999 and 2020. After matching 6 preoperative characteristics, there were 50 UHS and 50 FS patients. Patients who required acute type A aortic dissection repair, reoperations, concomitant procedures, or hypothermic circulatory arrest were excluded. RESULTS: In the matched sample, the hospital mortality rate was 1% (1 of 100). The median cardiopulmonary bypass time was 150 (interquartile range [IQR], 131 to 172) min and 164.5 (IQR, 138 to 190) min, respectively, for the UHS and FS groups (P = 0.08). The median aortic cross-clamp time was 121 (IQR, 107 to 139) min during UHS and 131 (IQR, 115 to 159) min during FS (P = 0.05). The median ventilation time was 7 (IQR, 3 to 14) h versus 17 (IQR, 10 to 24) h, respectively, after UHS and FS (P = 0.005). The median hospital length of stay was 7 (IQR, 6 to 9) days after UHS and 8 (IQR, 7 to 11) days after FS (P = 0.05). CONCLUSIONS: The low morbidity and mortality support the wider use of UHS for scAAR and AVR in appropriately selected patients. Larger studies are needed to confirm these initial findings.

Interventions to Increase Cancer Screening Adherence Among Somali Immigrants in the US and Europe: A Systematic Review.

Cancer screening rates among immigrant and refugee populations in high income countries is significantly lower than native born populations. The objective of this study is to systematically review the effectiveness of interventions to improve screening adherence for breast, cervical and colorectal cancer among Somali immigrants. A literature search was conducted for the years 2000-2021 and eight studies met eligibility criteria. The following intervention components were found to increase adherence to cervical cancer screening: home HPV test, educational workshop for women and education for general practitioners. A patient navigator intervention was found to increase screening for breast cancer. Educational workshops motivated or increased knowledge regarding cancer screening for breast, cervical and colorectal cancer. However, most of the studies had limitations due to methodology with potential for introduction of bias. Therefore, future studies comparing effectiveness of specific intervention components to reduce disparities in cancer screening among Somali immigrants and refugees are encouraged.

Evaluating the Impact of Pharmacist Dual Verification of Anticancer Therapy in the Modern Era.

Background: Pharmacist order verification is a critical step in ensuring medication safety for patients. While the second pharmacist verification (SPV) before dispensing anticancer therapies has been a longstanding practice, its continued necessity in the context of modern electronic health systems lacks robust evidence. Objective: This study aimed to assess the frequency of interventions performed by a second pharmacist to determine the ongoing effectiveness of the SPV process. Methods: This retrospective chart review was conducted at the Mayo Clinic, encompassing all anticancer therapy orders that necessitated an SPV. The study period extended from January 1, 2019, to June 30, 2021, and included inpatient and outpatient anticancer orders. The quantification and reporting of alterations made to discrete order fields subsequent to initial pharmacist verification of clinical significance were performed, utilizing the total number of anticancer therapy orders as the denominator. Results: Approximately 300 000 anticancer therapy orders were screened for inclusion criteria and 2.6% (N = 7634) of orders were modified on the SPV. Most changes were in the categories of rate (N = 1962), order start time (N = 1219), and pharmacy communication note (N = 777). Dosing changes greater than 10% accounted for 0.03% (N = 99) of the orders, with 10 anticancer therapies responsible for more than 50% of these changes. Conclusion and relevance: This study represents the largest report on the impact of SPV in a modern era. Our results suggest the SPV may be valuable for a small proportion of chemotherapy orders but raises questions about the necessity for broad application of this practice.