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Background: Stereotactic ablative radiation therapy (SBRT) is an emerging treatment option for primary renal cell carcinoma (RCC), particularly in patients who are unsuitable for surgery. The aim of this review is to assess the effect of increasing the biologically equivalent dose (BED) via various radiation fractionation regimens on clinical outcomes., Methods: A literature search was conducted in PubMed (Medline), EMBASE, and the Cochrane Library for studies published up to October 2023. Studies reporting on patients with localized RCC receiving SBRT were included to determine its effectiveness on local control, progression-free survival, and overall survival. A random effects model was used to meta-regress clinical outcomes relative to the BED for each study and heterogeneity was assessed by I 2 ., Results: A total of 724 patients with RCC from 22 studies were included, with a mean age of 72.7 years (range: 44.0-81.0). Local control was excellent with an estimate of 99 % (95 %CI: 97-100 %, I 2  = 19 %), 98 % (95 %CI: 96-99 %, I 2  = 8 %), and 94 % (95 %CI: 90-97 %, I 2  = 11 %) at one year, two years, and five years respectively. No definitive association between increasing BED and local control, progression-free survival and overall survival was observed. No publication bias was observed., Conclusions: A significant dose response relationship between oncological outcomes and was not identified, and excellent local control outcomes were observed at the full range of doses. Until new evidence points otherwise, we support current recommendations against routine dose escalation beyond 25-26 Gy in one fraction or 42-48 Gy in three fractions, and to consider de-escalation or compromising target coverage if required to achieve safe organ at risk doses., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RG: institutional grant funding- Astellas, TerSera. Honoraria: Bayer, Tolmar, Knight, TerSera. SR: Institutional grant funding – Astra Zeneca, Knight therapeutics. Honoraria – Bayer, Astra Zeneca, Tersera, Sanofi, Verity pharma., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Public health interventions to reduce maternal mortality have largely focused on obstetric causes of death. However, previous studies have noted that non-obstetrics factors, such as motor vehicle accidents, substance overdoses, homicides, and suicides, may account for a large proportion of maternal deaths. The study objective was to examine trends in maternal deaths from non-obstetric causes across races in the United States (US)., Methods: A population-based cross-sectional study was conducted on 80,710,348 live births using data from the "Birth Data" and "Mortality Multiple Cause" files compiled by the Centers for Disease Control and Prevention from 2000 to 2019. The annual incidence of maternal deaths attributed to non-obstetric causes (/100,000 live-births) during pregnancy and up to 42 days postpartum were calculated across racial groups. Then the effects of race on the risk of non-obstetric maternal mortality and temporal changes over the study period were examined using logistic regression models., Results: From 2000 to 2019, a total 7,334 women died during pregnancy, childbirth, and within 42 days postpartum from non-obstetric causes, representing 34.5% (7,334/21,241) of all maternal mortality. Of non-obstetric deaths, 31.3% were caused by transport accidents and 27.3% by accidental poisoning. American Indian women were found to have the highest risk of non-obstetric maternal mortality (OR 2.20,95% CI 1.90-2.56), and 46.1% (176/382) of all deaths among pregnant American Indian women were caused by non-obstetric complications. Risk of non-obstetric maternal mortality increased overall during the 20-year study period, with a greater increase among Black (1.15, 1.13-1.17) and American Indian women (1.17, 1.13-1.21)., Conclusion: Non-obstetric causes of death have become increasingly prevalent in the US, especially in American Indian women. Novel interventions to address these non-obstetric factors should especially target American Indian women to improve maternal outcomes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Bard by Google, a direct competitor to ChatGPT, was recently released. Understanding the relative performance of these different chatbots can provide important insight into their strengths and weaknesses as well as which roles they are most suited to fill. In this project, we aimed to compare the most recent version of ChatGPT, ChatGPT-4, and Bard by Google, in their ability to accurately respond to radiology board examination practice questions., Methods: Text-based questions were collected from the 2017-2021 American College of Radiology's Diagnostic Radiology In-Training (DXIT) examinations. ChatGPT-4 and Bard were queried, and their comparative accuracies, response lengths, and response times were documented. Subspecialty-specific performance was analyzed as well., Results: 318 questions were included in our analysis. ChatGPT answered significantly more accurately than Bard (87.11% vs 70.44%, P < .0001). ChatGPT's response length was significantly shorter than Bard's (935.28 ± 440.88 characters vs 1437.52 ± 415.91 characters, P < .0001). ChatGPT's response time was significantly longer than Bard's (26.79 ± 3.27 seconds vs 7.55 ± 1.88 seconds, P < .0001). ChatGPT performed superiorly to Bard in neuroradiology, (100.00% vs 86.21%, P = .03), general & physics (85.39% vs 68.54%, P < .001), nuclear medicine (80.00% vs 56.67%, P < .01), pediatric radiology (93.75% vs 68.75%, P = .03), and ultrasound (100.00% vs 63.64%, P < .001). In the remaining subspecialties, there were no significant differences between ChatGPT and Bard's performance., Conclusion: ChatGPT displayed superior radiology knowledge compared to Bard. While both chatbots display reasonable radiology knowledge, they should be used with conscious knowledge of their limitations and fallibility. Both chatbots provided incorrect or illogical answer explanations and did not always address the educational content of the question., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: Ophthalmology is reliant on effective interpretation of multimodal imaging to ensure diagnostic accuracy. The new ability of ChatGPT-4 (OpenAI) to interpret ophthalmic images has not yet been explored., Objective: To evaluate the performance of the novel release of an artificial intelligence chatbot that is capable of processing imaging data., Design, Setting, and Participants: This cross-sectional study used a publicly available dataset of ophthalmic cases from OCTCases, a medical education platform based out of the Department of Ophthalmology and Vision Sciences at the University of Toronto, with accompanying clinical multimodal imaging and multiple-choice questions. Across 137 available cases, 136 contained multiple-choice questions (99%)., Exposures: The chatbot answered questions requiring multimodal input from October 16 to October 23, 2023., Main Outcomes and Measures: The primary outcome was the accuracy of the chatbot in answering multiple-choice questions pertaining to image recognition in ophthalmic cases, measured as the proportion of correct responses. χ2 Tests were conducted to compare the proportion of correct responses across different ophthalmic subspecialties., Results: A total of 429 multiple-choice questions from 136 ophthalmic cases and 448 images were included in the analysis. The chatbot answered 299 of multiple-choice questions correctly across all cases (70%). The chatbot's performance was better on retina questions than neuro-ophthalmology questions (77% vs 58%; difference = 18%; 95% CI, 7.5%-29.4%; χ21 = 11.4; P < .001). The chatbot achieved a better performance on nonimage-based questions compared with image-based questions (82% vs 65%; difference = 17%; 95% CI, 7.8%-25.1%; χ21 = 12.2; P < .001).The chatbot performed best on questions in the retina category (77% correct) and poorest in the neuro-ophthalmology category (58% correct). The chatbot demonstrated intermediate performance on questions from the ocular oncology (72% correct), pediatric ophthalmology (68% correct), uveitis (67% correct), and glaucoma (61% correct) categories., Conclusions and Relevance: In this study, the recent version of the chatbot accurately responded to approximately two-thirds of multiple-choice questions pertaining to ophthalmic cases based on imaging interpretation. The multimodal chatbot performed better on questions that did not rely on the interpretation of imaging modalities. As the use of multimodal chatbots becomes increasingly widespread, it is imperative to stress their appropriate integration within medical contexts.

Purpose: To our knowledge, we present the first case series investigating the relationship between adaptive optics (AO) imaging and intravenous fluorescein angiography (IVFA) parameters in patients with diabetic retinopathy., Methods: Consecutive patients with diabetic retinopathy older than age 18 years presenting to a single center in Toronto, Canada, from 2020 to 2021 were recruited. Adaptive optics was performed with the RTX1 camera (Imagine Eyes, Orsay, France) at retinal eccentricities of 2° and 4°. Intravenous fluorescein angiography was assessed with the artificial intelligence-based RETICAD system to extract blood flow, perfusion, and blood-retinal-barrier (BRB) permeability at the same retinal locations. Correlations between AO and IVFA parameters were calculated using Pearson's correlation coefficient., Results: Across nine cases, a significant positive correlation existed between photoreceptor spacing on AO and BRB permeability (r = 0.303, P = 0.027), as well as perfusion (r = 0.272, P = 0.049) on IVFA. When stratified by location, a significant positive correlation between photoreceptor dispersion and both BRB permeability and perfusion (r = 0.770, P = 0.043; r = 0.846, P = 0.034, respectively) was observed. Cone density was also negatively correlated with BRB permeability (r = -0.819, P = 0.046)., Conclusion: Photoreceptor spacing on AO was significantly correlated with BRB permeability and perfusion on IVFA in patients with diabetic retinopathy. Future studies with larger sample sizes are needed to understand the relationship between AO and IVFA parameters in diverse patient populations.

Purpose: In the United States (US), deaths during pregnancy and childbirth have increased over the past 2 decades compared to other high-income countries, and there have been reports that racial disparities in maternal mortality have widened. The study objective was to examine recent trends in maternal mortality in the US by race., Methods: Our population-based cross-sectional study used data from the Centers for Disease Control and Prevention's 2000-2019 "Birth Data" and "Mortality Multiple Cause" data files from the US to calculate maternal mortality during pregnancy, childbirth, and puerperium across race. Logistic regression models estimated the effects of race on the risk of maternal mortality and examined temporal changes in risk across race., Results: A total of 21,241 women died during pregnancy and childbirth, with 65.5% caused by obstetrical complications and 34.5% by non-obstetrical causes. Black women, compared with White women, had greater risk of maternal mortality (OR 2.13, 95% CI 2.06-2.20), as did American Indian women (2.02, 1.83-2.24). Overall maternal mortality risk increased during the 20-year study period, with an annual increase of 2.4 and 4.7/100,000 among Black and American Indian women, respectively., Conclusions: Between 2000 and 2019, maternal mortality in the US increased, overall and especially in American Indian and Black women. Targeted public health interventions to improve maternal health outcomes should become a priority., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The existing T cell-centered immune checkpoint blockade therapies have been successful in treating some but not all patients with cancer. Immunosuppressive myeloid cells, including myeloid-derived suppressor cells (MDSC), that inhibit antitumor immunity and support multiple steps of tumor development are recognized as one of the major obstacles in cancer treatment. Leukocyte Ig-like receptor subfamily B3 (LILRB3), an immune inhibitory receptor containing tyrosine-based inhibitory motifs (ITIM), is expressed solely on myeloid cells. However, it is unknown whether LILRB3 is a critical checkpoint receptor in regulating the activity of immunosuppressive myeloid cells, and whether LILRB3 signaling can be blocked to activate the immune system to treat solid tumors. Here, we report that galectin-4 and galectin-7 induce activation of LILRB3 and that LILRB3 is functionally expressed on immunosuppressive myeloid cells. In some samples from patients with solid cancers, blockade of LILRB3 signaling by an antagonistic antibody inhibited the activity of immunosuppressive myeloid cells. Anti-LILRB3 also impeded tumor development in myeloid-specific LILRB3 transgenic mice through a T cell-dependent manner. LILRB3 blockade may prove to be a novel approach for immunotherapy of solid cancers., (©2023 American Association for Cancer Research.)

Purpose: To compare the efficacy and safety of pars plana vitrectomy with and without internal limiting membrane (ILM) peeling for macular hole (MH)., Methods: A systematic literature search on Ovid MEDLINE, Embase, Cochrane Library, and Google Scholar was performed from January 2000 to 2023. The primary outcome was the final best-corrected visual acuity (BCVA). Secondary outcomes included MH closure rates and the need for repeat surgery. The authors performed a random-effects meta-analysis on Review Manager 5.4., Results: Fourteen studies on 880 eyes were included. Pars plana vitrectomy with and without ILM peel achieved a similar final BCVA ( P = 0.66). However, pars plana vitrectomy without ILM peeling achieved a significantly better final BCVA in eyes with closed MHs (WMD = 0.05 logMAR, 95% CI, 0.01-0.10, P = 0.02). Pars plana vitrectomy with ILM peeling achieved a significantly higher primary MH closure rate (RR = 1.21, 95% CI, 1.04-1.42, P = 0.02) and lower incidence of MH reoperation (RR = 0.19, 95% CI, 0.11-0.33, P < 0.001). The final MH closure rate ( P = 0.12) and incidence of MH recurrence ( P = 0.25) were similar between groups., Conclusion: Pars plana vitrectomy with and without ILM peel achieved a similar final BCVA. However, pars plana vitrectomy without ILM peeling achieved a better final BCVA in eyes with closed MHs. ILM peeling achieved a greater primary MH closure rate and reduced need for reoperation.

Background: Cleft lip and/or palate (CL/P) is one of the most common congenital anomalies worldwide. Although CL/P management may require a series of interventions, mortality resulting from CL/P alone is rare. This study aims to examine recent trends of CL/P mortality rates in the USA., Methods: A retrospective population-based study was conducted using official US birth and death certificate data from the Centers for Disease Control and Prevention from 2000 to 2019. Annual mortality rates per 1000 births with CL/P were calculated across sex and racial groups. Multivariable logistic regression models estimated the effects of sex and race on the risk of mortality with CL/P, and linear regression models were used to examine temporal changes in mortality rate across sex and race., Results: From 2000 to 2019, 1119 deaths occurred in patients with documented CL/P, for an overall incidence of 20.3 deaths per 1000 births with CL/P (95% CI 18.9 to 22.8). Of these, Patau syndrome was the listed cause of death in 167 cases (14.9%). Black individuals (OR 1.93, 95% CI 1.85 to 2.01), Hispanic (1.54, 1.49 to 1.58) and American Indian individuals (1.28, 1.20 to 1.35) were at a greater risk of CL/P mortality compared with white individuals. Additionally, females were also at a greater risk (1.35, 1.21 to 1.49). A significant upward trend in CL/P mortality was observed in Hispanic (r 2 =0.70, p<0.01) and American Indian individuals (r 2 =0.81, p<0.01) from 2000 to 2019., Conclusions: Cleft birth and mortality surveillance is essential in healthcare and prevention planning. Future studies are required to understand the differences in CL/P mortality rates across various sociodemographic groups., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The influence of protected areas on the growth of African savannah elephant populations is inadequately known. Across southern Africa, elephant numbers grew at 0.16% annually for the past quarter century. Locally, much depends on metapopulation dynamics-the size and connections of individual populations. Population numbers in large, connected, and strictly protected areas typically increased, were less variable from year to year, and suffered less from poaching. Conversely, populations in buffer areas that are less protected but still connected have more variation in growth from year to year. Buffer areas also differed more in their growth rates, likely due to more threats and dispersal opportunities in the face of such dangers. Isolated populations showed consistently high growth due to a lack of emigration. This suggests that "fortress" conservation generally maintains high growth, while anthropogenic-driven source-sink dynamics within connected conservation clusters drive stability in core areas and variability in buffers.

Purpose: To determine sociodemographic predictors of poor vision in children and adolescents less than 18 years of age in a large, nationally representative sample of the US population., Design: Retrospective, population-based cross-sectional study., Methods: Using data from the 2021 National Health Interview Survey (NHIS), participants less than 18 years of age for whom data were available on vision difficulty were included in our analysis. Our primary outcome was vision difficulty. Sociodemographic variables were investigated as predictors of vision difficulty. Logistic regression models were performed using Stata version 17.0. An odds ratio (OR) and 95% CI were reported for analyses., Results: The 2021 NHIS reported on 8261 children and adolescents, of whom 7373 had data pertaining to vision difficulty and were included in our sample. Vision difficulty was associated with being unable to afford medical care (OR = 2.60, 95% CI = 1.17, 5.80, P = 0.02) and having public health insurance (OR = 1.52, 95% CI = 1.09, 2.12, P = .01). Compared to children less than 5 years of age, children ranging from 5 to 8 years (OR = 4.29, 95% CI = 2.26, 8.15, P < .01) and adolescents ranging from 16 to 17 years (OR = 6.06, 95% CI = 3.17, 11.58, P < .01) had a higher odds of vision difficulty. Compared to participants for whom the highest level of education of adults in their family was grade 1 to 11, the odds of vision difficulty were lower in those whose parents had a professional school or doctoral degree (OR = 0.30, 95% CI = 0.11, 0.84, P = .02)., Conclusions: Multiple sociodemographic factors are associated with vision difficulty in young persons. In working toward achieving equity in vision health, it is imperative that disparities mediated by sociodemographic factors be addressed through public health policies., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Children have been suggested to benefit from digit replantation due to a greater neurogenerative capacity. We aimed to conduct a systematic review on digit replantation in children to provide a comprehensive overview of survival rates and functional outcomes., Methods: A systematic literature search was conducted on Ovid MEDLINE, Embase, and the Cochrane Controlled Register of Trials for studies published between 1980 and 2023. We included peer-reviewed studies reporting on digit survival rates in pediatric patients under the age of 18 years who underwent single or multiple digit replantations distal to the metacarpophalangeal joint. Preoperative, intraoperative, and postoperative outcomes were extracted, and pooled estimates were derived using univariable analysis., Results: Twenty-two studies reporting on 761 patients and 814 digit replantations were included in our study. Most replantations occurred in the index (n = 74), Tamai zone I (n = 168), and from clean-cut injuries (n = 190). The mean survival rate was 76% (n = 618/814), with a mean range of motion at the distal interphalangeal joint ranging from 64 degrees to 90 degrees and two-point discrimination ranging from 3.8 mm to 6.4 mm. Compared with clean-cut injuries, digit replantations from avulsion [odds ratio (OR), 0.81; 95% confidence interval (CI), 0.74-0.89] or crush (OR, 0.71; 95% CI, 0.59-0.82) injuries were associated with a lower odds of survival. Digit replantations performed with two venous (OR, 1.43, 95% CI; 1.28-1.59) or arterial anastomoses (OR, 1.65; 95% CI, 1.48-1.81) were associated with a higher odds of survival., Conclusions: Our systematic review suggests that digit replantation may be a viable option in children. Further research is required to explore functionality after digit replantation in diverse pediatric populations., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

The immune checkpoint leukocyte immunoglobulin-like receptor B4 (LILRB4) is found specifically on the cell surface of acute monocytic leukemia (monocytic AML), an aggressive and common subtype of AML. We have developed a humanized monoclonal IgG 1 LILRB4-blocking antibody (h128-3), which improved immune regulation but reduced cell surface expression of LILRB4 in monocytic AML models by 40-60%. Interestingly, most of this effect was neutralized by mutation of the Fc region of the antibody (h128-3/N297A), which prevents interaction with Fc gamma receptors (FcγRs). This suggested that there is FcγR-dependent antigenic modulation underlying h128-3's effects, a mechanism known to alter the function of antibodies targeting B-cell malignancies. We disrupted the Fc-FcγR interaction pharmacologically and with stable CRISPR-Cas9-mediated genetic knockout of FcγRs in monocytic AML cell lines to investigate the role of FcγR-dependent antigenic modulation in the regulation of LILRB4 by h128-3. When FcγRI is inhibited or removed from the surface of monocytic AML cells, h128-3 cannot optimally perform its blocking function, resulting in activation of the LILRB4 inhibitory receptor and leading to a 15-25% decrease in T-cell-mediated cytotoxicity in vitro . In the absence of FcγRI, scaffolding by FcγRIIa allows h128-3 to maintain LILRB4-blocking function. Here we define a FcγR-dependent antigenic modulation mechanism underlying the function of an immunoreceptor blocking antibody for the first time in myeloid malignancy. This research will facilitate the development of safe, precision-targeted antibody therapeutics in myeloid malignancies with greater potency and efficacy., Competing Interests: Authors X.G., M.D., C.C.Z., N.Z. and Z.A. are listed as inventors in LILRB-relevant patent applications that were exclusively licensed to Immune-Onc Therapeutic, Inc. by the Board of Regents of the University of Texas System. Authors Z.A., N.Z. and C.C.Z. hold equity in and have Sponsored Research Agreements with Immune-Onc Therapeutics, Inc. M.D. and X.G. are Assistant Editors of Antibody Therapeutics. Z.A. holds the position of Deputy Editor-in-Chief for Antibody Therapeutics. They are blinded from reviewing or making decisions for the manuscript., (© The Author(s) 2023. Published by Oxford University Press on behalf of Antibody Therapeutics.)

The majority of the literature focused on whether consent should be extended to the adolescent population arises from themes adapted from American tort law. In contrast to the USA, Ontario does not delineate an age of consent for medical treatment and relying on American guidelines to guide practice in Ontario is problematic. While the literature is saturated with discussions for and against seeking adolescent consent, there are currently no bioethical guidelines on adolescent consent in the province of Ontario. This paper explores adolescent refusal of care and adolescent request for care in opposition to parental wishes. The paper seeks to answer the following questions: What is the difference between an adolescent and an adult in medical decision-making? What are the barriers to seeking adolescent consent? And, can the neurobiological argument be an accurate guide for obtaining adolescent consent?, Competing Interests: All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Large language model (LLM)-based chatbots are evolving at an unprecedented pace with the release of ChatGPT, specifically GPT-3.5, and its successor, GPT-4. Their capabilities in general-purpose tasks and language generation have advanced to the point of performing excellently on various educational examination benchmarks, including medical knowledge tests. Comparing the performance of these 2 LLM models to that of Family Medicine residents on a multiple-choice medical knowledge test can provide insights into their potential as medical education tools., Objective: This study aimed to quantitatively and qualitatively compare the performance of GPT-3.5, GPT-4, and Family Medicine residents in a multiple-choice medical knowledge test appropriate for the level of a Family Medicine resident., Methods: An official University of Toronto Department of Family and Community Medicine Progress Test consisting of multiple-choice questions was inputted into GPT-3.5 and GPT-4. The artificial intelligence chatbot's responses were manually reviewed to determine the selected answer, response length, response time, provision of a rationale for the outputted response, and the root cause of all incorrect responses (classified into arithmetic, logical, and information errors). The performance of the artificial intelligence chatbots were compared against a cohort of Family Medicine residents who concurrently attempted the test., Results: GPT-4 performed significantly better compared to GPT-3.5 (difference 25.0%, 95% CI 16.3%-32.8%; McNemar test: P<.001); it correctly answered 89/108 (82.4%) questions, while GPT-3.5 answered 62/108 (57.4%) questions correctly. Further, GPT-4 scored higher across all 11 categories of Family Medicine knowledge. In 86.1% (n=93) of the responses, GPT-4 provided a rationale for why other multiple-choice options were not chosen compared to the 16.7% (n=18) achieved by GPT-3.5. Qualitatively, for both GPT-3.5 and GPT-4 responses, logical errors were the most common, while arithmetic errors were the least common. The average performance of Family Medicine residents was 56.9% (95% CI 56.2%-57.6%). The performance of GPT-3.5 was similar to that of the average Family Medicine resident (P=.16), while the performance of GPT-4 exceeded that of the top-performing Family Medicine resident (P<.001)., Conclusions: GPT-4 significantly outperforms both GPT-3.5 and Family Medicine residents on a multiple-choice medical knowledge test designed for Family Medicine residents. GPT-4 provides a logical rationale for its response choice, ruling out other answer choices efficiently and with concise justification. Its high degree of accuracy and advanced reasoning capabilities facilitate its potential applications in medical education, including the creation of exam questions and scenarios as well as serving as a resource for medical knowledge or information on community services., (©Ryan ST Huang, Kevin Jia Qi Lu, Christopher Meaney, Joel Kemppainen, Angela Punnett, Fok-Han Leung. Originally published in JMIR Medical Education (https://mededu.jmir.org), 19.09.2023.)

Introduction: Although there have been reports of chemotherapy-induced nausea and vomiting (CINV) beyond 120 h, its overall prevalence has not been systematically examined. The aim of this review and meta-analysis was to report on the prevalence of this long-delayed CINV., Methods: This review was registered on PROSPERO (CRD42022346963). PubMed (Medline), Embase, and Cochrane Central were searched from inception until August 2022. Articles were included if they reported on CINV > 120 h after initiation of the chemotherapy regimen and patients received a single-agent highly emetogenic (HEC) or moderately emetogenic (MEC) antineoplastic agent for 1 day alone or in combination with low/minimal emetogenic chemotherapy. For all eligible articles, individual study authors were contacted and requested to provide individual patient-level data of demographics, emetogenicity of chemotherapy regimens, and daily incidence of nausea and vomiting. Forward stepwise logistic regression identified predictors for the incident day's CINV based on prior day's CINV episodes, controlling for patient demographics, and stratified by regimen emetogenicity., Results: A total of 2048 patients from 2 studies were included in this individual patient data meta-analysis: 1333 patients (65%) received HEC and 715 (35%) received MEC. Among those receiving HEC, 325 (24%) experienced acute, 652 (49%) delayed, and 393 (31%) long-delayed nausea; 107 (8%) experienced acute, 179 (14%) delayed, and 79 (6%) long-delayed vomiting. Among those receiving MEC, 48 (7%) experienced acute, 272 (38%) delayed, and 167 (24%) long-delayed nausea; 12 (2%) experienced acute, 97 (14%) delayed, and 42 (6%) long-delayed vomiting. Nausea in the long-delayed phase was as severe as in the delayed phase. Patients experiencing nausea and vomiting on days 4 and 5 were at significant risk of experiencing long-delayed CINV., Conclusion: While not as prevalent as delayed nausea and vomiting, long-delayed CINV affects a significant proportion of patients and severity is similar. Patients with delayed CINV, specifically on days 4-5, are at risk of experiencing long-delayed CINV., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In recent decades, mass spectrometry-based lipidomics has provided a fertile environment for scientific investigations of biochemical and mechanistic processes in biological systems. Notably, this approach has been used to characterize physiological and pathological processes relevant to the central nervous system by identifying changes in the sphingolipid content in the brain, cerebral spinal fluid, and blood plasma. However, despite a preponderance of studies identifying correlations between specific lipids and disease progression, this powerful resource has not yet substantively translated into clinically useful diagnostic assays. Part of this gap may be explained by insufficient depth of the lipidomic profiles in many studies, by lab-to-lab inconsistencies in methodology, and a lack of absolute quantification. These issues limit the identification of specific molecular species and the harmonization of results across independent studies. In this chapter, we contextualize these issues with recent reports identifying correlations between brain lipids and neurological diseases, and we describe the workflow our group has optimized for analysis of the blood plasma sphingolipidome, adapted to the characterization of the human brain tissue., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Children with complex health needs (CCHN) have intersecting medical, behavioral health, and social needs. Unfortunately, fragmentation across health and social services sectors often results in uncoordinated care for CCHN and their families., Objective: The purpose of this article is to describe the creation of a statewide cross-sector partnership, the Children's Complex Care Coalition of North Carolina, to identify and act on opportunities for system-level improvements in the care of CCHN., Methods: We applied a virtual community engagement approach to form an advisory committee of cross-sector collaborators; systematically identify priorities most important and urgent to collaborators for improving systems of care; and host a series of virtual convenings involving more than 90 attendees from across the state to operationalize collaborator-identified priorities into actionable next steps., Lessons Learned: Key facilitators of success for the Children's Complex Care Coalition of North Carolina partnership were investing time in building trusting relationships, particularly with families of CCHN, and aligning goals and priorities with existing local and regional efforts. Challenges included incorporating traditionally under-represented perspectives, right-sizing virtual convening attendance and number of topics covered, and navigating technological difficulties in a virtual environment., Conclusions: Health systems can catalyze the formation of cross-sector coalitions and community partnerships to advance complex care. Virtual convenings with interactive activities and participatory structures can be an efficient medium to connect coalition members and elicit actionable recommendations for system-level improvements that address the needs of community members.

Objectives: In this study, we sought to evaluate whether older patients with hearing loss who underwent surgery were at greater risk of postsurgical complications, increased inpatient length-of-stay (LOS), and hospital readmission., Design: This was a retrospective cohort study of patients receiving surgery at a tertiary medical center. Utilizing electronic health record data from two merged datasets, we identified patients 65 years and older, undergoing major surgery between January 1, 2014 and January 31, 2017, and who had audiometric evaluation before surgery. Patients were classified as having either normal hearing or hearing loss based on pure-tone average in the better ear. A Generalized Estimating Equations approach was used to fit multivariable regression models for outcome variables of interest., Results: Of patients ≥65 years undergoing major surgery in our time frame, a total of 742 surgical procedures were performed on 621 patients with available audiometric data. After adjusting for age, sex, race, and comorbidities, hearing loss was associated with an increase in the odds of developing postoperative complications. Every 10 dB increase in hearing loss was associated with a 14% increase in the odds of developing a postoperative complication (odds ratio = 1.14, 95% confidence interval = 1.01-1.29, p = 0.031). Hearing loss was not significantly associated with increased hospital LOS, 30-day readmission, or 90-day readmission., Conclusions: Hearing loss was significantly associated with developing postoperative complications in older adults undergoing major surgery. Screening for hearing impairment may be a useful addition to the preoperative assessment and perioperative management of older patients undergoing surgery., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Although emerging evidence suggests that hearing loss (HL) is an independent risk factor for falls, it is unclear how HL may impact falls risk in adults with vestibular dysfunction and nonvestibular dizziness. The purpose of this study was to characterize the impact of HL on falls in patients with vestibular dysfunction and nonvestibular dizziness relative to a group of patients without dizziness. In addition, this study aimed to evaluate whether there was an interactive effect between HL and vestibular dysfunction or nonvestibular dizziness on the odds of falling., Design: The authors conducted a retrospective cross-sectional study of 2,750 adult patients with dizziness evaluated at a tertiary care center vestibular clinic between June 1, 2015, and October 7, 2020. Only patients with available self-reported falls status, as extracted from the electronic medical record, were included. Patients were classified into the following diagnostic groups based on rotary chair testing and videonystagmography: benign paroxysmal positional vertigo (BPPV, n = 255), unilateral vestibular hypofunction (UVH, n = 456), bilateral vestibular hypofunction (BVH, n = 38), central dysfunction (n = 208), multiple diagnoses (n = 109), and dizzy, nonvestibular (n = 1,389). A control group of patients without dizziness (n = 295) was identified by a random sample of audiology patients. Degree of HL was characterized by the 4-frequency pure tone average (PTA) (0.5, 1, 2, and 4 kHz) of the better hearing ear. Demographic variables, comorbidities, cognitive impairment status, and falls-associated medications were extracted from the electronic medical record and included as covariates during analysis. Potential associations between PTA and falls status and possible interactions between diagnostic group and PTA were explored using multivariate logistic regression., Results: The BVH and central dysfunction groups had the highest rates of self-reported falls at 26.3% and 26.9%, respectively. The control group had the lowest rate of self-reported falls at 6.4%. With the exception of the multiple diagnoses group, all diagnostic groups had elevated odds of falling compared with the control group, when adjusting for demographics, comorbidities, cognitive impairment status, and falls-associated medications. There was no significant association between degree of HL and falls status (odds ratio [OR] = 1.02; 95% confidence interval [CI] = 0.93, 1.11; p = 0.713) when adjusting for diagnostic group and all other covariates. Furthermore, there were no significant interactions between diagnostic group and degree of HL on the odds of falling., Conclusions: These results indicate that HL was not associated with falls in patients with vestibular dysfunction or nonvestibular dizziness, while adjusting for demographics, comorbidities, and falls-associated medications. There was no significant interactive effect observed between HL and vestibular dysfunction or nonvestibular dizziness on the odds of falling. As previously reported, vestibular dysfunction and nonvestibular dizziness were independently associated with falls relative to a group of patients without dizziness. A population-based study utilizing more robust falls data is needed to explore a potential association between HL and falls in those with vestibular dysfunction., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Accurate maps of species ranges are essential to inform conservation, but time-consuming to produce and update. Given the pace of change of knowledge about species distributions and shifts in ranges under climate change and land use, a need exists for timely mapping approaches that enable batch processing employing widely available data. We develop a systematic approach of batch-processing range maps and derived Area of Habitat maps for terrestrial bird species with published ranges below 125,000 km2 in Central and South America. (Area of Habitat is the habitat available to a species within its range.) We combine existing range maps with the rapidly expanding crowd-sourced eBird data of presences and absences from frequently surveyed locations, plus readily accessible, high resolution satellite data on forest cover and elevation to map the Area of Habitat available to each species. Users can interrogate the maps produced to see details of the observations that contributed to the ranges. Previous estimates of Areas of Habitat were constrained within the published ranges and thus were, by definition, smaller-typically about 30%. This reflects how little habitat within suitable elevation ranges exists within the published ranges. Our results show that on average, Areas of Habitat are 12% larger than published ranges, reflecting the often-considerable extent that eBird records expand the known distributions of species. Interestingly, there are substantial differences between threatened and non-threatened species. Some 40% of Critically Endangered, 43% of Endangered, and 55% of Vulnerable species have Areas of Habitat larger than their published ranges, compared with 31% for Near Threatened and Least Concern species. The important finding for conservation is that threatened species are generally more widespread than previously estimated., Competing Interests: The authors have declared that no competing interests exist. The views expressed in this publication do not necessarily reflect those of IUCN.

Background and Purpose- Although there are no trials or large cohorts to inform clinical care, current guidelines caution against giving intravenous tPA (tissue-type plasminogen activator) to patients with acute ischemic stroke who are taking non-vitamin K antagonist oral anticoagulants (NOACs). We performed a literature review of intravenous tPA in patients treated with NOACs preceding stroke. Methods- A literature search of PubMed was performed encompassing January 2010 to March 2018. Patient characteristics, timing of last medication intake, laboratory testing, use of reversal, and outcomes ≤3 months after discharge were summarized. Results- We identified 55 studies with 492 NOAC patients receiving tPA (dabigatran, 181; rivaroxaban, 215; apixaban, 40; and unspecified NOAC, 56). Among patients with complete data, the median time from the last NOAC intake to symptom onset was 8 hours (interquartile range, 2.5-14.5), with 55.2% (80/145) within 12 hours. Few patients underwent sensitive laboratory tests, such as thrombin time, diluted thrombin time, or anti-Xa assays before tPA administration. The overall observed rates of symptomatic intracranial hemorrhage, mortality, and favorable outcomes (National Institutes of Health Stroke Scale score, ≤1; modified Rankin Scale score, 0-2; or neurological improvement in the National Institutes of Health Stroke Scale score, ≥8 points) were 4.3% (20/462), 11.3% (48/423), and 43.7% (164/375), respectively. Among dabigatran-treated patients, reversal with idarucizumab was associated with fewer symptomatic intracranial hemorrhage (4.5% [2/44] versus 7.4% [8/108]; unadjusted odds ratio, 0.60; 95% CI, 0.12-2.92), death (4.5% [2/44] versus 12.0% [13/108]; unadjusted odds ratio, 0.35; 95% CI, 0.08-1.61), and more favorable outcomes (79.1% [34/43] versus 39.2% [29/74]; unadjusted odds ratio, 5.86; 95% CI, 2.45-14.00), although the differences were not statistically significant for symptomatic intracranial hemorrhage and death. Conclusions- These preliminary observations suggest that tPA may be reasonably well tolerated without prohibitive risks of bleeding complications in selected patients on NOACs. Reversal of anticoagulant effects by idarucizumab for dabigatran-treated patients before tPA is an emerging strategy that was associated with more favorable outcomes.