A Comprehensive Evaluation of Emergency Department Utilization by Patients With Cirrhosis.

INTRODUCTION: Emergency department (ED)-based care is required for cirrhosis management, yet the burden of cirrhosis-related ED healthcare utilization is understudied. We aimed to describe ED utilization within a statewide health system and compare the outcomes of high ED use (HEDU) vs non-HEDU in individuals with cirrhosis. METHODS: We retrospectively reviewed charts of adults with cirrhosis who presented to any of 16 EDs within the Indiana University Health system in 2021. Patient characteristics, features of the initial ED visit, subsequent 90-day healthcare use, and 360-day outcomes were collected. Multivariable logistic regression models were used to identify predictors HEDU status which was defined as ≥2 ED visits within 90 days after the index ED visit. RESULTS: There were 2,124 eligible patients (mean age 61.3 years, 53% male, and 91% White). Major etiologies of cirrhosis were alcohol (38%), metabolic dysfunction-associated steatohepatitis (27%), and viral hepatitis (21%). Cirrhosis was newly diagnosed in the ED visit for 18.4%. Most common reasons for ED visits were abdominal pain (21%), shortness of breath (19%), and ascites/volume overload (16%). Of the initial ED visits, 20% (n = 424) were potentially avoidable. The overall 90-day mortality was 16%. Within 90 days, there were 366 HEDU (20%). Notable variables independently associated with HEDU were model for end-stage liver disease-sodium (adjusted odds ratio [aOR] 1.044, 95% confidence interval [CI] 1.005-1.085), prior ED encounter (aOR 1.520, 95% CI 1.136-2.034), and avoidable initial ED visit (aOR 1.938, 95% CI 1.014-3.703). DISCUSSION: Abdominal pain, shortness of breath, and ascites/fluid overload are the common presenting reasons for ED visits for patients with cirrhosis. Patients with cirrhosis presenting to the ED experience a 90-day mortality rate of 16%, and among those who initially visited the ED, 20% were HEDU. We identified several variables independently associated with HEDU. Our observations pave the way for developing interventions to optimize the care of patients with cirrhosis presenting to the ED and to lower repeated ED visits.

Letter to the editor RE: Management of Anterior Urethral Stricture: A survey of Contemporary Practice of Iranian Urologists.

We read with interest the recent paper by Hosseini et al detailing the management practice of Iranian Urologists towards the management of anterior urethral stricture disease. Please find our letter to the editor regarding this.

Peripartum Cardiac Arrest with Terminal QRS Distortion: A Case Report.

Introduction: Peripartum cardiac arrest is increasing in incidence. While pulmonary embolism (PE) remains an important cause of peripartum morbidity and mortality, other cardiovascular emergencies such as myocardial infarction (MI) are now the leading cause of pregnancy-related death. Emergency physicians (EP) need to be well versed in subtle electrocardiographic (ECG) signs of coronary ischemia to better care for peripartum patients in cardiac arrest. Case Report: A 38-year-old gravida 2 parity1 female three days post-partum presented in cardiac arrest. After approximately 12 minutes of Advanced Cardiac Life Support including electric defibrillation, the patient experienced sustained return of spontaneous circulation. The physician team was primarily concerned for PE based on an initial ECG demonstrating terminal QRS distortion in V2 but no ST-segment elevation myocardial infarction (STEMI). Computed tomography angiography (CTA) of the chest did not reveal PE. Repeat ECG after CTA demonstrated STEMI criteria, and the patient was emergently taken to the cardiac catheterization laboratory where she was found to have 99% occlusion of the left anterior descending artery. Conclusion: Emergency physicians should have a high index of suspicion for MI when managing peripartum patients in cardiac arrest. The ECG findings specific for coronary-occlusive acute MI but not included in the classic STEMI criteria increase accuracy and prevent delays in diagnosis; however, the clinical uptake of this paradigm has been slow. Early recognition of terminal QRS distortion can help EPs more rapidly diagnose the etiology of cardiac arrest.

Diagnostic accuracy of prehospital lung ultrasound for acute decompensated heart failure: A systematic review and Meta-analysis.

BACKGROUND: Lung ultrasound (LUS) reduces time to diagnosis and treatment of acute decompensated heart failure (ADHF) in emergency department (ED) patients with undifferentiated dyspnea. We conducted a systematic review to evaluate the diagnostic accuracy and clinical impact of LUS for ADHF in the prehospital setting. METHODS: We performed a keyword search of multiple databases from inception through June 1, 2023. Included studies were those enrolling prehospital patients with undifferentiated dyspnea or suspected ADHF, and specifically diagnostic studies comparing prehospital LUS to a gold standard and intervention studies with a non-US comparator group. Title and abstract screening, full text review, risk of bias (ROB) assessments, and data extraction were performed by multiple authors. and adjudicated. The primary outcome was pooled sensitivity, specificity, and diagnostic likelihood ratios (LR) for prehospital LUS. A test-treatment threshold of 0.7 was applied based on prior ADHF literature in the ED. Intervention outcomes included mortality, mechanical ventilation, and time to HF specific treatment. RESULTS: Eight diagnostic studies (n = 691) and two intervention studies (n = 70) met inclusion criteria. No diagnostic studies were low-ROB. Both intervention studies were critical-ROB, and not pooled. Pooled sensitivity and specificity of prehospital LUS for ADHF were 86.7% (95%CI:70.8%-94.6%) and 87.5% (78.2%-93.2%), respectively, with similar performance by physician vs. paramedic LUS and number of lung zones evaluated. Pooled LR+ and LR- were 7.27 (95% CI: 3.69-13.10) and 0.17 (95% CI: 0.06-0.34), respectively. Area under the summary receiver operating characteristic curve was 0.922. At the observed 42.4% ADHF prevalence (pre-test probability), positive pre-hospital LUS exceeded the 70% threshold to initiate treatment (post-test probability 84%, 80-88%). CONCLUSIONS: LUS had similar diagnostic test characteristics for ADHF diagnosis in the prehospital setting as in the ED. A positive prehospital LUS may be sufficient to initiate early ADHF treatment based on published test-treatment thresholds. More studies are needed to determine the clinical impact of prehospital LUS.

Short-Stay Units vs Routine Admission From the Emergency Department in Patients With Acute Heart Failure: The SSU-AHF Randomized Clinical Trial.

Importance: More than 80% of patients who present to the emergency department (ED) with acute heart failure (AHF) are hospitalized. With more than 1 million annual hospitalizations for AHF in the US, safe and effective alternatives are needed. Care for AHF in short-stay units (SSUs) may be safe and more efficient than hospitalization, especially for lower-risk patients, but randomized clinical trial data are lacking. Objective: To compare the effectiveness of SSU care vs hospitalization in lower-risk patients with AHF. Design, Setting, and Participants: This multicenter randomized clinical trial randomly assigned low-risk patients with AHF 1:1 to SSU or hospital admission from the ED. Patients received follow-up at 30 and 90 days post discharge. The study began December 6, 2017, and was completed on July 22, 2021. The data were analyzed between March 27, 2020, and November 11, 2023. Intervention: Randomized post-ED disposition to less than 24 hours of SSU care vs hospitalization. Main Outcomes and Measures: The study was designed to detect at least 1-day superiority for a primary outcome of days alive and out of hospital (DAOOH) at 30-day follow-up for 534 participants, with an allowance of 10% participant attrition. Due to the COVID-19 pandemic, enrollment was truncated at 194 participants. Before unmasking, the primary outcome was changed from DAOOH to an outcome with adequate statistical power: quality of life as measured by the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). The KCCQ-12 scores range from 0 to 100, with higher scores indicating better quality of life. Results: Of the 193 patients enrolled (1 was found ineligible after randomization), the mean (SD) age was 64.8 (14.8) years, 79 (40.9%) were women, and 114 (59.1%) were men. Baseline characteristics were balanced between arms. The mean (SD) KCCQ-12 summary score between the SSU and hospitalization arms at 30 days was 51.3 (25.7) vs 45.8 (23.8) points, respectively (P = .19). Participants in the SSU arm had 1.6 more DAOOH at 30-day follow-up than those in the hospitalization arm (median [IQR], 26.9 [24.4-28.8] vs 25.4 [22.0-27.7] days; P = .02). Adverse events were uncommon and similar in both arms. Conclusions and Relevance: The findings show that the SSU strategy was no different than hospitalization with regard to KCCQ-12 score, superior for more DAOOH, and safe for lower-risk patients with AHF. These findings of lower health care utilization with the SSU strategy need to be definitively tested in an adequately powered study. Trial Registration: ClinicalTrials.gov Identifier: NCT03302910.

Emergency department management of patients with right heart failure.

Right heart failure (RHF) can result from many cardiac, pulmonary, and systemic pathologies. Common causes of RHF include pulmonary embolism, left heart failure, congenital heart disease, chronic lung disease, acute myocardial infarction, infiltrative disease, infectious disease, and valvular abnormalities. Acute and chronic RHF confer a high risk for morbidity and mortality in the acute care setting, and interventions commonly used in emergency care can prompt acute decompensation if the RHF is not recognized. The severity of presentation may range from compensated clinically silent cardiovascular dysfunction to venous congestion, multiorgan failure, and circulatory collapse. This review describes the pathophysiology of right heart failure and offers an evidence-based approach to the diagnosis, management, and disposition of both acute and chronic RHF.

The prognostic value of improving congestion on lung ultrasound during treatment for acute heart failure differs based on patient characteristics at admission.

BACKGROUND: Lung ultrasound congestion scoring (LUS-CS) is a congestion severity biomarker. The BLUSHED-AHF trial demonstrated feasibility for LUS-CS-guided therapy in acute heart failure (AHF). We investigated two questions: 1) does change (∆) in LUS-CS from emergency department (ED) to hospital-discharge predict patient outcomes, and 2) is the relationship between in-hospital decongestion and adverse events moderated by baseline risk-factors at admission? METHODS: We performed a secondary analysis of 933 observations/128 patients from 5 hospitals in the BLUSHED-AHF trial receiving daily LUS. ∆LUS-CS from ED arrival to inpatient discharge (scale -160 to +160, where negative = improving congestion) was compared to a primary outcome of 30-day death/AHF-rehospitalization. Cox regression was used to adjust for mortality risk at admission [Get-With-The-Guidelines HF risk score (GWTG-RS)] and the discharge LUS-CS. An interaction between ∆LUS-CS and GWTG-RS was included, under the hypothesis that the association between decongestion intensity (by ∆LUS-CS) and adverse outcomes would be stronger in admitted patients with low-mortality risk but high baseline congestion. RESULTS: Median age was 65 years, GWTG-RS 36, left ventricular ejection fraction 36 %, and ∆LUS-CS -20. In the multivariable analysis ∆LUS-CS was associated with event-free survival (HR = 0.61; 95 % CI: 0.38-0.97), while discharge LUS-CS (HR = 1.00; 95%CI: 0.54-1.84) did not add incremental prognostic value to ∆LUS-CS alone. As GWTG-RS rose, benefits of LUS-CS reduction attenuated (interaction p < 0.05). ∆LUS-CS and event-free survival were most strongly correlated in patients without tachycardia, tachypnea, hypotension, hyponatremia, uremia, advanced age, or history of myocardial infarction at ED/baseline, and those with low daily loop diuretic requirements. CONCLUSIONS: Reduction in ∆LUS-CS during AHF treatment was most associated with improved readmission-free survival in heavily congested patients with otherwise reassuring features at admission. ∆LUS-CS may be most useful as a measure to ensure adequate decongestion prior to discharge, to prevent early readmission, rather than modify survival.

Small bowel obstruction secondary to phytobezoar in a patient with myotonic dystrophy.

A male patient in his 30s, with myotonic dystrophy (DM), presented to the emergency department with abdominal pain and vomiting. CT imaging revealed a soft tissue lesion in the terminal ileum causing small bowel obstruction (SBO). The patient underwent diagnostic laparoscopy which allowed identification and removal of the obstructing lesion. This was in the form of an intact, undigested potato, a phytobezoar. Bezoars are collections of undigested material found in the gastrointestinal (GI) tract, a phytobezoar is composed of plant material and is the most common form of bezoar. DM is a multisystem disorder characterised by skeletal muscle weakness, however it often presents with GI symptoms and the muscles of mastication are often affected. DM is a known risk factor for bezoar formation and should be considered as an important differential in DM patients presenting with SBO.

Haemorrhagic cholecystitis in a young patient, complicated by gallbladder perforation and choledocholithiasis.

Haemorrhagic cholecystitis is a rare condition associated with a high risk of morbidity and mortality. Its pathophysiology is thought to be due to gallbladder wall erosion and infarction secondary to inflammation, which subsequently leads to haemorrhage into the gallbladder lumen or the peritoneal cavity. There is no current official guidance on optimal management of this condition. We describe a case of a female patient in her 40s who presented with right upper quadrant pain, followed by haematemesis. After CT scan, a diagnosis of haemorrhagic cholecystitis was made and initially managed conservatively. In this case, haemorrhagic cholecystitis was later complicated by gallbladder perforation and choledocholithiasis. Definitive management was with emergency open cholecystectomy. We believe this to be the first reported case of haemorrhagic cholecystitis complicated by gallbladder perforation and choledocholithiasis. This report highlights the need for early definitive management of haemorrhagic cholecystitis to prevent subsequent complications.

The significance of historical troponin elevation in acute heart failure: Not as reassuring as previously assumed.

BACKGROUND: Historical cardiac troponin (cTn) elevation is commonly interpreted as lessening the significance of current cTn elevations at presentation for acute heart failure (AHF). Evidence for this practice is lacking. Our objective was to determine the incremental prognostic significance of historical cTn elevation compared to cTn elevation and ischemic heart disease (IHD) history at presentation for AHF. METHODS: A total of 341 AHF patients were prospectively enrolled at five sites. The composite primary outcome was death/cardiopulmonary resuscitation, mechanical cardiac support, intubation, new/emergent dialysis, and/or acute myocardial infarction (AMI)/percutaneous coronary intervention (PCI)/coronary artery bypass grafting (CABG) at 90 days. Secondary outcomes were 30-day AMI/PCI/CABG and in-hospital AMI. Logistic regression compared outcomes versus initial emergency department (ED) cTn, the most recent electronic medical record cTn, estimated glomerular filtration rate, age, left ventricular ejection fraction, and IHD history (positive, negative by prior coronary workup, or unknown/no prior workup). RESULTS: Elevated cTn occurred in 163 (49%) patients, 80 (23%) experienced the primary outcome, and 29 had AMI (9%). cTn elevation at ED presentation, adjusted for historical cTn and other covariates, was associated with the primary outcome (adjusted odds ratio [aOR] 2.39, 95% confidence interval [CI] 1.30-4.38), 30-day AMI/PCI/CABG, and in-hospital AMI. Historical cTn elevation was associated with greater odds of the primary outcome when IHD history was unknown at ED presentation (aOR 5.27, 95% CI 1.24-21.40) and did not alter odds of the outcome with known positive (aOR 0.74, 95% CI 0.33-1.70) or negative IHD history (aOR 0.79, 95% CI 0.26-2.40). Nevertheless, patients with elevated ED cTn were more likely to be discharged if historical cTn was also elevated (78% vs. 32%, p = 0.025). CONCLUSIONS: Historical cTn elevation in AHF patients is a harbinger of worse outcomes for patients who have not had a prior IHD workup and should prompt evaluation for underlying ischemia rather than reassurance for discharge. With known IHD history, historical cTn elevation was neither reassuring nor detrimental, failing to add incremental prognostic value to current cTn elevation alone.

Comparison of pulmonary congestion severity using artificial intelligence-assisted scoring versus clinical experts: A secondary analysis of BLUSHED-AHF.

AIM: Acute decompensated heart failure (ADHF) is the leading cause of cardiovascular hospitalizations in the United States. Detecting B-lines through lung ultrasound (LUS) can enhance clinicians' prognostic and diagnostic capabilities. Artificial intelligence/machine learning (AI/ML)-based automated guidance systems may allow novice users to apply LUS to clinical care. We investigated whether an AI/ML automated LUS congestion score correlates with expert's interpretations of B-line quantification from an external patient dataset. METHODS AND RESULTS: This was a secondary analysis from the BLUSHED-AHF study which investigated the effect of LUS-guided therapy on patients with ADHF. In BLUSHED-AHF, LUS was performed and B-lines were quantified by ultrasound operators. Two experts then separately quantified the number of B-lines per ultrasound video clip recorded. Here, an AI/ML-based lung congestion score (LCS) was calculated for all LUS clips from BLUSHED-AHF. Spearman correlation was computed between LCS and counts from each of the original three raters. A total of 3858 LUS clips were analysed on 130 patients. The LCS demonstrated good agreement with the two experts' B-line quantification score (r = 0.894, 0.882). Both experts' B-line quantification scores had significantly better agreement with the LCS than they did with the ultrasound operator's score (p < 0.005, p < 0.001). CONCLUSION: Artificial intelligence/machine learning-based LCS correlated with expert-level B-line quantification. Future studies are needed to determine whether automated tools may assist novice users in LUS interpretation.

Paramagnetic States in Oxygen-Doped Boron Nitride Extend Light Harvesting and Photochemistry to the Deep Visible Region.

A family of boron nitride (BN)-based photocatalysts for solar fuel syntheses have recently emerged. Studies have shown that oxygen doping, leading to boron oxynitride (BNO), can extend light absorption to the visible range. However, the fundamental question surrounding the origin of enhanced light harvesting and the role of specific chemical states of oxygen in BNO photochemistry remains unanswered. Here, using an integrated experimental and first-principles-based computational approach, we demonstrate that paramagnetic isolated OB3 states are paramount to inducing prominent red-shifted light absorption. Conversely, we highlight the diamagnetic nature of O-B-O states, which are shown to cause undesired larger band gaps and impaired photochemistry. This study elucidates the importance of paramagnetism in BNO semiconductors and provides fundamental insight into its photophysics. The work herein paves the way for tailoring of its optoelectronic and photochemical properties for solar fuel synthesis.

Treatment and outcome variation in out-of-hospital cardiac arrest among four urban hospitals in Detroit.

AIMS: To determine whether out-of-hospital cardiac arrest (OHCA) post-resuscitation management and outcomes differ between four Detroit hospitals. INTRODUCTION: Significant variation exists in treatment/outcomes from OHCA. Disparities between hospitals serving a similar population is not well known. METHODS: Retrospective OHCA data was collected from the Detroit-Cardiac Arrest Registry (DCAR) between January 2014 to December 2019. Four hospitals were compared on two treatments (angiography, do not resuscitate (DNR)) and two outcomes (cerebral performance category (CPC) ≤ 2, in-hospital death). Models for death and CPC were tested with and without coronary angiography and DNR status. RESULTS: 999 patients at hospitals A - D differed (p < 0.05) before multivariable adjustment by age, race, witnessed arrest, dispatch-emergency department (ED) time, TTM, coronary angiography, DNR order, and in-hospital death. Rates of death and CPC ≤ 2 were worse in Hospital A (82.8%, 10%, respectively) compared to others (69.1%, 14.1%). After multivariable adjustment, Hospital A performed angiography less compared to B (OR = 0.17) and was more likely to initiate new DNR status than B (OR = 2.9), C (OR = 16.1), or D (OR = 3.6). CPC ≤ 2 were worse in Hospital A compared to B (OR = 0.27) and D (OR = 0.35). After sensitivity analysis, CPC ≤ 2 odds did not differ for A versus B (OR = 0.58, adjusted for angiography) or D (OR = 0.65, adjusted for DNR). Odds of death, despite angiography and DNR differences, were worse in Hospital A compared to B (OR = 1.87) and D (OR = 1.81). CONCLUSION: Differing rates of DNR and coronary angiography was associated with observed disparities in favorable neurologic outcome, but not death, between four Detroit hospitals.

Role of electron localisation in H adsorption and hydride formation in the Mg basal plane under aqueous corrosion: a first-principles study.

Understanding hydrogen-metal interactions is important in various fields of surface science, including the aqueous corrosion of metals. The interaction between atomic H and a Mg surface is a key process for the formation of sub-surface Mg hydride, which may play an important role in Mg aqueous corrosion. In the present work, we performed first-principles Density Functional Theory (DFT) calculations to study the mechanisms for hydrogen adsorption and crystalline Mg hydride formation under aqueous conditions. The Electron Localisation Function (ELF) is found to be a promising indicator for predicting stable H adsorption in the Mg surface. It is found that H adsorption and hydride layer formation is dominated by high ELF adsorption sites. Our calculations suggest that the on-surface adsorption of atomic H, OH radicals and atomic O could enhance the electron localisation at specific sites in the sub-surface region, thus forming effective H traps locally. This is predicted to result in the formation of a thermodynamically stable sub-surface hydride layer, which is a potential precursor of the crucial hydride corrosion product of magnesium.

Pharmacodynamic Biomarkers for Biosimilar Development and Approval: A Workshop Summary.

The US Food and Drug Administration (FDA) Biosimilars Guidance describes how biosimilars may be approved based on clinical pharmacokinetic and pharmacodynamic (PD) biomarker data, without comparative clinical studies with efficacy end points. This type of clinical development program, however, has only been implemented for a small number of FDA-approved biosimilar products over the last decade. To encourage the use of PD biomarkers in biosimilar development and approval, the Duke-Margolis Center for Health Policy collaborated with the FDA to host a two-day virtual public workshop entitled "Pharmacodynamic Biomarkers for Biosimilar Development and Approval" on September 20-21, 2021. The public workshop was a forum for global regulators, biopharmaceutical developers, and academic researchers to discuss the current and future role of PD biomarkers in improving the efficiency of biosimilar development and approval. The workshop objectives included: (i) discuss the current and potential future state of leveraging PD biomarkers for biosimilar development and approval; (ii) summarize the FDA's initiatives to advance biosimilar development; (iii) describe stakeholders' experience with PD biomarkers in biosimilar development; and (iv) explain research efforts to promote broader application of PD biomarkers in biosimilar development. This document summarizes presentations and panel discussions from each session of the two-day September 2021 public workshop covering the application of PD biomarkers for biosimilar development.

Mind the Interface Gap: Exposing Hidden Interface Defects at the Epitaxial Heterostructure between CuO and Cu2O.

Well designed and optimized epitaxial heterostructures lie at the foundation of materials development for photovoltaic, photocatalytic, and photoelectrochemistry applications. Heterostructure materials offer tunable control over charge separation and transport at the same time preventing recombination of photogenerated excitations at the interface. Thus, it is of paramount importance that a detailed understanding is developed as the basis for further optimization strategies and design. Oxides of copper are nontoxic, low cost, abundant materials with a straightforward and stable manufacturing process. However, in individual applications, they suffer from inefficient charge transport of photogenerated carriers. Hence, in this work, we investigate the role of the interface between epitaxially aligned CuO and Cu2O to explore the potential benefits of such an architecture for more efficient electron and hole transfer. The CuO/Cu2O heterojunction nature, stability, bonding mechanism, interface dipole, electronic structure, and band bending were rationalized using hybrid density functional theory calculations. New electronic states are identified at the interface itself, which are originating neither from lattice mismatch nor strained Cu-O bonds. They form as a result of a change in coordination environment of CuO surface Cu2+ cations and an electron transfer across the interface Cu1+-O bond. The first process creates occupied defect-like electronic states above the valence band, while the second leaves hole states below the conduction band. These are constitutional to the interface and are highly likely to contribute to recombination effects competing with the improved charged separation from the suitable band bending and alignment and thus would limit the expected output photocurrent and photovoltage. Finally, a favorable effect of interstitial oxygen defects has been shown to allow for band gap tunability at the interface but only to the point of the integral geometrical contact limit of the heterostructure itself.

Strain-Tuneable Magnetism and Spintronics of Distorted Monovacancies in Graphene.

The electronic and spintronic properties of the monovacancies in freestanding and isotopically compressed graphene are investigated using hybrid exchange density functional perturbation theory. When the effects of electronic self-interaction are taken into account, an integer magnetic moment of 2 µB is identified for a Jahn-Teller reconstructed V1(5-9) monovacancy in freestanding graphene. For graphene with stable ripples induced by a compressive strain of 5%, a bond reconstruction produces a V1(55-66) structure for the monovacancy, which is localized at the saddle points of the ripple. The sizeable local distortion induced by reconstruction modifies both the geometric and electronic properties of rippled graphene and quenches the magnetic moment of the vacancy due to the sp3 hybridization of the central atom. The nonmagnetic V1(55-66) structure is found to be stable on rippled structures, with the formation energy ∼2.3 eV lower than that of the metastable distorted V1(5-9) structures localized at sites other than the saddle points. The electronic ground state of distorted V1(5-9) corresponds to a wide range of fractional magnetic moments (0.50-1.25 µB). The computed relative stabilities and the electronic and magnetic properties of the V1(5-9) structures are found to be closely related to their local distortions. This analysis of the fundamental properties of defective graphene under compression suggests a number of strategies for generating regular defect patterns with tuneable magnetic and electronic properties and may, therefore, be used as a novel technique to achieve more precise control of graphene electronic structure for various application scenarios such as transistors, strain sensors, and directed chemisorption.