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Contextualizing India's Medicolegal Controversies Related to Brain Death/Death by Neurologic Criteria: Regulation, Religion, and Resource Allocation

Lewis, Ariane; Zirpe, Kapil
Brain death/death by neurologic criteria (BD/DNC) is accepted as legal death throughout much of the world. The World Brain Death Project and a subsequent review of the literature through 2023 highlighted several medicolegal controversies related to BD/DNC in Canada, the United Kingdom, and the United States but did not discuss medicolegal controversies related to BD/DNC in low- and middle-income countries, such as India. Although the Transplantation of Human Organs Act of 1994 acknowledged BD/DNC as death in India, BD/DNC evaluations are not always completed when BD/DNC is suspected. This has been attributed to lack of awareness/acceptance by medical professionals, lack of public awareness/acceptance of BD/DNC, communication challenges, fear, time limitations, and the inclusion of BD/DNC in organ donation law (but not general law). There has been a gradual rise in the number of donations after BD/DNC (a correlate for the number of BD/DNC determinations) in southern and western states, but the number of donations after BD/DNC has decreased in the southwestern state of Kerala in the setting of recent medicolegal controversies. This article reviews the history of BD/DNC determination in India as a whole, then describes the recent medicolegal controversies related to BD/DNC in the state of Kerala. Finally, these controversies are contextualized relative to the aforementioned controversies in high-income countries. Three key international themes of medicolegal controversies related to BD/DNC are regulation, religion, and resource allocation. The global neurocritical care community must advocate for consistency and accuracy in BD/DNC determination and collaborate with legal and policy experts to develop means to mitigate these challenges through revisions to the law, standardization of practice and policies, education, and communication.
PMID: 40537723
ISSN: 1556-0961
CID: 5871232

Hybrid machine learning for real-time prediction of edema trajectory in large middle cerebral artery stroke

Phillips, Ethan; O'Donoghue, Odhran; Zhang, Yumeng; Tsimpos, Panos; Mallinger, Leigh Ann; Chatzidakis, Stefanos; Pohlmann, Jack; Du, Yili; Kim, Ivy; Song, Jonathan; Brush, Benjamin; Smirnakis, Stelios; Ong, Charlene J; Orfanoudaki, Agni
In treating malignant cerebral edema after a large middle cerebral artery stroke, clinicians need quantitative tools for real-time risk assessment. Existing predictive models typically estimate risk at one, early time point, failing to account for dynamic variables. To address this, we developed Hybrid Ensemble Learning Models for Edema Trajectory (HELMET) to predict midline shift severity, an established indicator of malignant edema, over 8-h and 24-h windows. The HELMET models were trained on retrospective data from 623 patients and validated on 63 patients from a different hospital system, achieving mean areas under the receiver operating characteristic curve of 96.6% and 92.5%, respectively. By integrating transformer-based large language models with supervised ensemble learning, HELMET demonstrates the value of combining clinician expertise with multimodal health records in assessing patient risk. Our approach provides a framework for accurate, real-time estimation of dynamic clinical targets using human-curated and algorithm-derived inputs.
PMCID:12084630
PMID: 40379753
ISSN: 2398-6352
CID: 5844852

Later midline shift is associated with better post-hospitalization discharge status after large middle cerebral artery stroke

Song, Jonathan J; Stafford, Rebecca A; Pohlmann, Jack E; Kim, Ivy So Yeon; Cheekati, Maanyatha; Dennison, Sydney; Brush, Benjamin; Chatzidakis, Stefanos; Huang, Qiuxi; Smirnakis, Stelios M; Gilmore, Emily J; Mohammed, Shariq; Abdalkader, Mohamad; Benjamin, Emelia J; Dupuis, Josée; Greer, David M; Ong, Charlene J
Space occupying cerebral edema is a feared complication after large ischemic stroke, occurring in up to 30% of patients with middle cerebral artery (MCA) occlusion and peaking 2-4 days after injury. Little is known about the factors and outcomes associated with peak edema timing, especially after 96 h. We aimed to characterize differences and compare discharge status between patients who experienced maximum midline shift (MLS) or decompressive hemicraniectomy (DHC) in the acute (< 48 h), average (48-96 h), and subacute (> 96 h) groups. We performed a two-center, retrospective study of patients with ≥ 1/2 MCA territory infarct and MLS. We constructed a multivariable model to test the association of subacute peak edema and favorable discharge status, adjusting for various confounders. Of 321 eligible patients, 32%, 36%, and 32% experienced acute, average, and subacute peak edema. Subacute peak edema was significantly associated with higher odds of favorable discharge than acute peak edema (aOR, 2.05; 95% CI, 1.03-4.11). Subacute peak edema after large MCA stroke is associated with better discharge status compared to acute peak edema courses. Understanding how the timing of cerebral edema affects risk of unfavorable discharge has important implications for treatment decisions and prognostication.
PMID: 40188256
ISSN: 2045-2322
CID: 5819562

Kidney Function Following COVID-19 in Children and Adolescents

Li, Lu; Zhou, Ting; Lu, Yiwen; Chen, Jiajie; Lei, Yuqing; Wu, Qiong; Arnold, Jonathan; Becich, Michael J; Bisyuk, Yuriy; Blecker, Saul; Chrischilles, Elizabeth; Christakis, Dimitri A; Geary, Carol Reynolds; Jhaveri, Ravi; Lenert, Leslie; Liu, Mei; Mirhaji, Parsa; Morizono, Hiroki; Mosa, Abu S M; Onder, Ali Mirza; Patel, Ruby; Smoyer, William E; Taylor, Bradley W; Williams, David A; Dixon, Bradley P; Flynn, Joseph T; Gluck, Caroline; Harshman, Lyndsay A; Mitsnefes, Mark M; Modi, Zubin J; Pan, Cynthia G; Patel, Hiren P; Verghese, Priya S; Forrest, Christopher B; Denburg, Michelle R; Chen, Yong; ,
IMPORTANCE/UNASSIGNED:It remains unclear whether children and adolescents with SARS-CoV-2 infection are at heightened risk for long-term kidney complications. OBJECTIVE/UNASSIGNED:To investigate whether SARS-CoV-2 infection is associated with an increased risk of postacute kidney outcomes among pediatric patients, including those with preexisting kidney disease or acute kidney injury (AKI). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This retrospective cohort study used data from 19 health institutions in the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) initiative from March 1, 2020, to May 1, 2023 (follow-up ≤2 years completed December 1, 2024; index date cutoff, December 1, 2022). Participants included children and adolescents (aged <21 years) with at least 1 baseline visit (24 months to 7 days before the index date) and at least 1 follow-up visit (28 to 179 days after the index date). EXPOSURES/UNASSIGNED:SARS-CoV-2 infection, determined by positive laboratory test results (polymerase chain reaction, antigen, or serologic) or relevant clinical diagnoses. A comparison group included children with documented negative test results and no history of SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Outcomes included new-onset chronic kidney disease (CKD) stage 2 or higher or CKD stage 3 or higher among those without preexisting CKD; composite kidney events (≥50% decline in estimated glomerular filtration rate [eGFR], eGFR ≤15 mL/min/1.73 m2, dialysis, transplant, or end-stage kidney disease diagnosis), and at least 30%, 40%, or 50% eGFR decline among those with preexisting CKD or acute-phase AKI. Hazard ratios (HRs) were estimated using Cox proportional hazards regression models with propensity score stratification. RESULTS/UNASSIGNED:Among 1 900 146 pediatric patients (487 378 with and 1 412 768 without COVID-19), 969 937 (51.0%) were male, the mean (SD) age was 8.2 (6.2) years, and a range of comorbidities was represented. SARS-CoV-2 infection was associated with higher risk of new-onset CKD stage 2 or higher (HR, 1.17; 95% CI, 1.12-1.22) and CKD stage 3 or higher (HR, 1.35; 95% CI, 1.13-1.62). In those with preexisting CKD, COVID-19 was associated with an increased risk of composite kidney events (HR, 1.15; 95% CI, 1.04-1.27) at 28 to 179 days. Children with acute-phase AKI had elevated HRs (1.29; 95% CI, 1.21-1.38) at 90 to 179 days for composite outcomes. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this large US cohort study of children and adolescents, SARS-CoV-2 infection was associated with a higher risk of adverse postacute kidney outcomes, particularly among those with preexisting CKD or AKI, suggesting the need for vigilant long-term monitoring.
PMCID:11992607
PMID: 40214993
ISSN: 2574-3805
CID: 5824322

Principles of reversal of anticoagulation in patients with intracerebral hemorrhage related to oral anticoagulants

Christensen, Hanne; Casolla, Barbara; Frontera, Jennifer A; Grundtvig, Josefine; Nielsen, Jørn Dalsgaard; Petersson, Jesper; Steiner, Thorsten
The incidence of intracerebral hemorrhage (ICH) associated with oral anticoagulants (OAC) is about one in five cases of ICH and associated with severe clinical presentation, frequently rapid clinical deterioration, and 30-days mortality of app 50%. This narrative review gives an overview of presentation and acute treatment of OAC-ICH. Oral anticoagulants do not cause ICH but lead to prolongation of bleeding and higher risk of hematoma expansion (HE). Clinicoradiological characteristics of oral anticoagulant associated ICH are not different from ICH in general. The therapeutic principle of reversal is to prevent or limit HE. The mode of action of the reversal agents for vitamin K antagonists, direct oral thrombin inhibitor and direct oral factor Xa inhibitors are described in the main text. We also discuss the principles of blood pressure lowering in the setting of acute OAC-ICH as it may be the second driving force of HE. Stroke unit care is needed to prevent further complications. Data from randomized controlled trials and observational data from unselected patients are needed to make stronger and more precise recommendations on acute therapy.
PMCID:12098318
PMID: 40401657
ISSN: 2396-9881
CID: 5853312

Factors Associated With Stroke Recurrence After Initial Diagnosis of Cervical Artery Dissection

Mandel, Daniel M; Shu, Liqi; Chang, Christopher; Jack, Naomi; Leon Guerrero, Christopher R; Henninger, Nils; Muppa, Jayachandra; Affan, Muhammad; Ul Haq Lodhi, Omair; Heldner, Mirjam R; Antonenko, Kateryna; Seiffge, David; Arnold, Marcel; Salehi Omran, Setareh; Crandall, Ross; Lester, Evan; Lopez Mena, Diego; Arauz, Antonio; Nehme, Ahmad; Boulanger, Marion; Touze, Emmanuel; Sousa, Joao Andre; Sargento-Freitas, Joao; Barata, Vasco; Castro-Chaves, Paulo; Brito, Maria Teresa; Khan, Muhib; Mallick, Dania; Rothstein, Aaron; Khazaal, Ossama; Kaufman, Josefin E; Engelter, Stefan T; Traenka, Christopher; Aguiar de Sousa, Diana; Soares, Mafalda; Rosa, Sara; Zhou, Lily W; Gandhi, Preet; Field, Thalia S; Mancini, Steven; Metanis, Issa; Leker, Ronen R; Pan, Kelly; Dantu, Vishnu; Baumgartner, Karl; Burton, Tina; von Rennenberg, Regina; Nolte, Christian H; Choi, Richard; MacDonald, Jason; Bavarsad Shahripour, Reza; Guo, Xiaofan; Ghannam, Malik; Almajali, Mohammad; Samaniego, Edgar A; Sanchez, Sebastian; Rioux, Bastien; Zine-Eddine, Faycal; Poppe, Alexandre; Fonseca, Ana Catarina; Fortuna Baptista, Maria; Cruz, Diana; Romoli, Michele; De Marco, Giovanna; Longoni, Marco; Keser, Zafer; Griffin, Kim; Kuohn, Lindsey; Frontera, Jennifer; Amar, Jordan; Giles, James; Zedde, Marialuisa; Pascarella, Rosario; Grisendi, Ilaria; Nzwalo, Hipolito; Liebeskind, David S; Molaie, Amir; Cavalier, Annie; Kam, Wayneho; Mac Grory, Brian; Al Kasab, Sami; Anadani, Mohammad; Kicielinski, Kimberly; Eltatawy, Ali; Chervak, Lina; Chulluncuy Rivas, Roberto; Aziz, Yasmin; Bakradze, Ekaterina; Tran, Thanh Lam; Rodrigo Gisbert, Marc; Requena, Manuel; Saleh Velez, Faddi; Ortiz Gracia, Jorge; Muddasani, Varsha; de Havenon, Adam; Vishnu, Venugopalan Y; Yaddanapudi, Sridhara; Adams, Latasha; Browngoehl, Abigail; Ranasinghe, Tamra; Dunston, Randy; Lynch, Zachary; Penckofer, Mary; Siegler, James E; Mayer, Silvia; Willey, Joshua; Zubair, Adeel; Cheng, Yee Kuang; Sharma, Richa; Marto, João Pedro; Mendes Ferreira, Vítor; Klein, Piers; Nguyen, Thanh N; Asad, Syed Daniyal; Sarwat, Zoha; Balabhadra, Anvesh; Patel, Shivam; Secchi, Thais; Martins, Sheila; Mantovani, Gabriel; Kim, Young Dae; Krishnaiah, Balaji; Elangovan, Cheran; Lingam, Sivani; Quereshi, Abid; Fridman, Sebastian; Alvarado, Alonso; Khasiyev, Farid; Linares, Guillermo; Mannino, Marina; Terruso, Valeria; Vassilopoulou, Sofia; Tentolouris-Piperas, Vasileios; Martinez Marino, Manuel; Carrasco Wall, Victor; Indraswari, Fransisca; El Jamal, Sleiman; Liu, Shilin; Alvi, Muhammad; Ali, Farman; Sarvath, Mohammed; Morsi, Rami Z; Kass-Hout, Tareq; Shi, Feina; Zhang, Jinhua; Sokhi, Dilraj; Said, Jamil; Mongare, Newnex; Simpkins, Alexis; Gomez, Roberto; Sen, Shayak; Ghani, Mohammad; Elnazeir, Marwa; Xiao, Han; Kala, Narendra; Khan, Farhan; Stretz, Christoph; Mohammadzadeh, Nahid; Goldstein, Eric; Furie, Karen; Yaghi, Shadi
BACKGROUND/UNASSIGNED:Patients presenting with cervical artery dissection (CAD) are at risk for subsequent ischemic events. We aimed to identify characteristics that are associated with increased risk of ischemic stroke after initial presentation of CAD and to evaluate the differential impact of anticoagulant versus antiplatelet therapy in these high-risk individuals. METHODS/UNASSIGNED:This was a preplanned secondary analysis of the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection), a multicenter international retrospective observational study (63 sites from 16 countries in North America, South America, Europe, Asia, and Africa) that included patients with CAD predominantly between January 2015 and June 2022. The primary outcome was subsequent ischemic stroke by day 180 after diagnosis. Clinical and imaging variables were compared between those with versus without subsequent ischemic stroke. Significant factors associated with subsequent stroke risk were identified using stepwise Cox regression. Associations between subsequent ischemic stroke risk and antithrombotic therapy type (anticoagulation versus antiplatelets) among patients with identified risk factors were explored using adjusted Cox regression. RESULTS/UNASSIGNED:=0.01). CONCLUSIONS/UNASSIGNED:In this post hoc analysis of the STOP-CAD study, several factors associated with subsequent ischemic stroke were identified among patients with CAD. Furthermore, we identified a potential benefit of anticoagulation in patients with CAD with occlusive dissection. These findings require validation by meta-analyses of prior studies to formulate optimal treatment strategies for specific high-risk CAD subgroups.
PMID: 40143807
ISSN: 1524-4628
CID: 5816392

The Neurologist's Imperative in Brain Death

Greer, David M; Lewis, Ariane; Kirschen, Matthew P
PMID: 40126488
ISSN: 2168-6157
CID: 5814692

Unplanned extubation prevention in the neuroscience ICU at a High Reliability Organization

Aladin, Meagan; Buckley, Lauren; Maloney, Meghan; Rojanaporn, Pimsiri; Gombar, Theresa; Lewis, Ariane
BACKGROUND:Intubated neuroscience ICU patients are at risk for unplanned extubation (premature removal of the endotracheal tube by the patient or during patient care). The incidence of unplanned extubation is an indicator of the quality of ICU care. Unplanned extubation is a risk factor for pneumonia, increased ventilator days, the need for tracheostomy and increased ICU and hospital length-of-stay. After serial unplanned extubations, we introduced a multidisciplinary unit-based practice standard to reduce unplanned extubations as part of a quality improvement initiative in the neuroscience ICU in a large academic medical center at a High Reliability Organization in May 2021. The unit-based practice standard to guide care of intubated neuroscience ICU patients focused on communication, timely escalation of concerns, use of sedation/analgesia targeting RASS ≤ -1, soft wrist restraints (unless specified exclusion criteria met) and continuous observation for patients at high risk of agitation/restlessness. We sought to determine the impact of this initiative on the incidence of unplanned extubations. METHOD/METHODS:Unplanned extubations were identified via retrospective audit of prospective incident reports from our Patient Safety Incident registry pre-initiative (June 2020-May 2021) and prospective audit of incident reports post-initiative (July 2021-March 2024). Chart review facilitated collection of data on patient age, sex, diagnosis, intubation day, RASS goal, sedation/analgesia, restraints, constant observation, shift, and reintubation. The total number of intubated patients and ventilator days during these timeframes was identified retrospectively via an electronic medical record report of all patients on ventilators in the neuroscience ICU. RESULTS:During the pre-initiative audit period, there were 214 intubated patients (968 ventilator days). The audit identified 9 unplanned extubations (0.93/100 ventilator days; 8 males, median age 63-years-old (IQR 47-67)). There were 4 patients who were not ordered for sedation/analgesia or had a RASS goal of 0 and no patients were in nonviolent soft wrist restraints. During the post-initiative audit period, there were 576 intubated patients (2,730 ventilator days). The audit identified 6 unplanned extubations (0.22/100 ventilator days; 6 males, median age 53-years-old (IQR 27-78)). All 6 patients had a RASS goal ≤ -1 and were in nonviolent soft wrist restraints. CONCLUSION/CONCLUSIONS:This quality improvement initiative effectively reduced the incidence of unplanned extubations in our neuroscience ICU.
PMID: 40068249
ISSN: 1532-2653
CID: 5808362

Impact of COVID-19 on functional, cognitive, neuropsychiatric, and health-related outcomes in patients with dementia: A systematic review

Crivelli, Lucia; Winkler, Andrea; Keller, Greta; Beretta, Simone; Calandri, Ismael Luis; De Groote, Wouter; Fornari, Arianna; Frontera, Jennifer; Kivipelto, Miia; Lopez-Rocha, Ana Sabsil; Mangialasche, Francesca; Munblit, Daniel; Palmer, Katie; Guekht, Alla; Allegri, Ricardo
BACKGROUND/UNASSIGNED:This systematic review analyzes the impact of COVID-19 on dementia patients' functional, cognitive, neuropsychiatric, and health related outcomes. It hypothesizes that dementia patients infected with SARS-CoV-2experience more pronounced deterioration compared to those who are uninfected. METHODS/UNASSIGNED:Research from 01/03/2020 to 07/10/2023 was conducted using Medline, Web of Science, and Embase databases, and adhering to PRISMA guidelines and the PICO framework. The study aimed to determine if SARS-CoV-2 infection is associated with worse outcomes in dementia patients. The protocol is registered in PROSPERO (CRD42022352481), and bias was evaluated using the Newcastle-Ottawa Scale. RESULTS/UNASSIGNED:Among 198 studies reviewed, only three met the criteria. Chen et al. (2023) identified higher mortality in SARS-CoV-2-infected dementia patients, while Merla et al. (2023) observed faster cognitive decline in infected individuals with increased hospital admissions. Additionally, Cascini et al. (2022) reported an increased risk of infection and significantly elevated mortality in dementia patients, highlighting comorbidities and antipsychotic medication use as key risk factors. CONCLUSION/UNASSIGNED:These limited data suggest higher mortality and cognitive decline in dementia patients following COVID-19, underscoring the need for extensive research in this area.
PMCID:11663964
PMID: 39720103
ISSN: 2405-6502
CID: 5767462

Predicting hematoma expansion after intracerebral hemorrhage: a comparison of clinician prediction with deep learning radiomics models

Yu, Boyang; Melmed, Kara R; Frontera, Jennifer; Zhu, Weicheng; Huang, Haoxu; Qureshi, Adnan I; Maggard, Abigail; Steinhof, Michael; Kuohn, Lindsey; Kumar, Arooshi; Berson, Elisa R; Tran, Anh T; Payabvash, Seyedmehdi; Ironside, Natasha; Brush, Benjamin; Dehkharghani, Seena; Razavian, Narges; Ranganath, Rajesh
BACKGROUND:Early prediction of hematoma expansion (HE) following nontraumatic intracerebral hemorrhage (ICH) may inform preemptive therapeutic interventions. We sought to identify how accurately machine learning (ML) radiomics models predict HE compared with expert clinicians using head computed tomography (HCT). METHODS:We used data from 900 study participants with ICH enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 Study. ML models were developed using baseline HCT images, as well as admission clinical data in a training cohort (n = 621), and their performance was evaluated in an independent test cohort (n = 279) to predict HE (defined as HE by 33% or > 6 mL at 24 h). We simultaneously surveyed expert clinicians and asked them to predict HE using the same initial HCT images and clinical data. Area under the receiver operating characteristic curve (AUC) were compared between clinician predictions, ML models using radiomic data only (a random forest classifier and a deep learning imaging model) and ML models using both radiomic and clinical data (three random forest classifier models using different feature combinations). Kappa values comparing interrater reliability among expert clinicians were calculated. The best performing model was compared with clinical predication. RESULTS:The AUC for expert clinician prediction of HE was 0.591, with a kappa of 0.156 for interrater variability, compared with ML models using radiomic data only (a deep learning model using image input, AUC 0.680) and using both radiomic and clinical data (a random forest model, AUC 0.677). The intraclass correlation coefficient for clinical judgment and the best performing ML model was 0.47 (95% confidence interval 0.23-0.75). CONCLUSIONS:We introduced supervised ML algorithms demonstrating that HE prediction may outperform practicing clinicians. Despite overall moderate AUCs, our results set a new relative benchmark for performance in these tasks that even expert clinicians find challenging. These results emphasize the need for continued improvements and further enhanced clinical decision support to optimally manage patients with ICH.
PMID: 39920546
ISSN: 1556-0961
CID: 5784422