Faculty Bibliography

INTRODUCTION/UNASSIGNED:Older adults undergoing surgery are at risk of postoperative neurocognitive disorders, prompting the need for preoperative cognitive screening in this population. Traditionally, cognitive screening has been conducted in-person using brief assessment tools such as the Montreal Cognitive Assessment (MoCA) or the Mini-Mental State Examination (MMSE). More comprehensive test batteries, such as the Uniform Data Set (UDS) Neuropsychological Battery, and its remote testing version, the Uniform Data Set version 3 tele-adapted test battery (UDS v3.0 T-cog), have been developed to assess cognitive decline in normal aging and disease conditions, but have not been applied in the perioperative setting. METHODS/UNASSIGNED:We assessed the feasibility of using this remote UDS v3.0 T-cog battery for preoperative cognitive assessment in 81 older adults 65+ scheduled for lower extremity joint replacement surgery. RESULTS/UNASSIGNED:Our results indicate that the UDS v3.0 T-cog achieves 99% completion rates and demonstrates high patient satisfaction. Further, we found 28% of subjects were cognitively impaired in this patient cohort. DISCUSSION/UNASSIGNED:These findings suggest that the UDS v3.0 T-cog is a feasible tool for assessing cognitive function in the older adult perioperative population. To our knowledge, this is the first study to apply this comprehensive remote test battery in the preoperative setting.

The provision of positive pressure ventilation has the potential to provoke hemodynamic deterioration. The subject of heart-lung interactions is both complex and critical yet often obscure and fraught with misconception among trainees and seasoned clinicians alike. In this article, we focus on the impact of positive pressure ventilation on the right heart, providing a teaching approach composed of didactic sessions and simulated cases. We split our didactics and cases into two 30-minute sessions: "How the right heart fills" and "How the right heart empties." Within each session, our framework highlights key concepts with respect to circulatory physiology, respiratory system mechanics, and an amalgam of the two subjects as it pertains to managing clinical scenarios encountered during a trainee's intensive care unit rotation.

Myeloid cells are known to suppress antitumour immunity¹. However, the molecular drivers of immunosuppressive myeloid cell states are not well defined. Here we used single-cell RNA sequencing of human and mouse non-small cell lung cancer (NSCLC) lesions, and found that in both species the type 2 cytokine interleukin-4 (IL-4) was predicted to be the primary driver of the tumour-infiltrating monocyte-derived macrophage phenotype. Using a panel of conditional knockout mice, we found that only deletion of the IL-4 receptor IL-4Rα in early myeloid progenitors in bone marrow reduced tumour burden, whereas deletion of IL-4Rα in downstream mature myeloid cells had no effect. Mechanistically, IL-4 derived from bone marrow basophils and eosinophils acted on granulocyte-monocyte progenitors to transcriptionally programme the development of immunosuppressive tumour-promoting myeloid cells. Consequentially, depletion of basophils profoundly reduced tumour burden and normalized myelopoiesis. We subsequently initiated a clinical trial of the IL-4Rα blocking antibody dupilumab^2-5 given in conjunction with PD-1/PD-L1 checkpoint blockade in patients with relapsed or refractory NSCLC who had progressed on PD-1/PD-L1 blockade alone (ClinicalTrials.gov identifier NCT05013450 ). Dupilumab supplementation reduced circulating monocytes, expanded tumour-infiltrating CD8 T cells, and in one out of six patients, drove a near-complete clinical response two months after treatment. Our study defines a central role for IL-4 in controlling immunosuppressive myelopoiesis in cancer, identifies a novel combination therapy for immune checkpoint blockade in humans, and highlights cancer as a systemic malady that requires therapeutic strategies beyond the primary disease site.

Colchicine has an expanding role in cardiovascular disease treatment. Colchicine overdose is a toxicologic emergency. Direct cellular toxicity interferes with myocardial contractility, leading to cardiovascular collapse. We present a case of a patient with a colchicine overdose supported with venoarterial extracorporeal membrane oxygenation, highlighting the challenges and limitations.

BACKGROUND:Ischemic heart disease is a leading cause of death globally with a disproportionate burden in low- and middle-income countries (LMICs). Natural language processing (NLP) allows for data enrichment in large datasets to facilitate key clinical research. We used NLP to assess gender differences in symptoms and management of patients hospitalized with acute myocardial infarction (AMI) at Aga Khan University Hospital-Pakistan. OBJECTIVE:The primary objective of this study was to use NLP to assess gender differences in the symptoms and management of patients hospitalized with AMI at a tertiary care hospital in Pakistan. METHODS:We developed an NLP-based methodology to extract AMI symptoms and medications from 5358 discharge summaries spanning the years 1988 to 2018. This dataset included patients admitted and discharged between January 1, 1988, and December 31, 2018, who were older than 18 years with a primary discharge diagnosis of AMI (using ICD-9 [International Classification of Diseases, Ninth Revision], diagnostic codes). The methodology used a fuzzy keyword-matching algorithm to extract AMI symptoms from the discharge summaries automatically. It first preprocesses the free text within the discharge summaries to extract passages indicating the presenting symptoms. Then, it applies fuzzy matching techniques to identify relevant keywords or phrases indicative of AMI symptoms, incorporating negation handling to minimize false positives. After manually reviewing the quality of extracted symptoms in a subset of discharge summaries through preliminary experiments, a similarity threshold of 80% was determined. RESULTS:Among 1769 women and 3589 men with AMI, women had higher odds of presenting with shortness of breath (odds ratio [OR] 1.46, 95% CI 1.26-1.70) and lower odds of presenting with chest pain (OR 0.65, 95% CI 0.55-0.75), even after adjustment for diabetes and age. Presentation with abdominal pain, nausea, or vomiting was much less frequent but consistently more common in women (P<.001). "Ghabrahat," a culturally distinct term for a feeling of impending doom was used by 5.09% of women and 3.69% of men as presenting symptom for AMI (P=.06). First-line medication prescription (statin and β-blockers) was lower in women: women had nearly 30% lower odds (OR 0.71, 95% CI 0.57-0.90) of being prescribed statins, and they had 40% lower odds (OR 0.67, 95% CI 0.57-0.78) of being prescribed β-blockers. CONCLUSIONS:Gender-based differences in clinical presentation and medication management were demonstrated in patients with AMI at a tertiary care hospital in Pakistan. The use of NLP for the identification of culturally nuanced clinical characteristics and management is feasible in LMICs and could be used as a tool to understand gender disparities and address key clinical priorities in LMICs.

Various radiologic examinations and other diagnostic tools exist for evaluating gastrointestinal diseases. When symptoms of gastrointestinal disease persist and no underlying anatomic or structural abnormality is identified, the diagnosis of functional gastrointestinal disorder is frequently applied. Given its physiologic and quantitative nature, scintigraphy often plays a central role in the diagnosis and treatment of patients with suspected functional gastrointestinal disorder. Most frequently, after functional gallbladder disease is excluded, gastric emptying scintigraphy (GES) is considered the next step in evaluating patients with suspected gastric motility disorder who present with upper gastrointestinal symptoms such as dyspepsia or bloating. GES is the standard modality for detecting delayed gastric emptying (gastroparesis) and the less commonly encountered clinical entity, gastric dumping syndrome. Additionally, GES can be used to assess abnormalities of intragastric distribution, suggesting specific disorders such as impaired fundal accommodation or antral dysfunction, as well as to evaluate gastric emptying of liquid. More recently, scintigraphic examinations for evaluating small bowel and large bowel transit have been developed and validated for routine diagnostic use. These can be performed individually or as part of a comprehensive whole-gut transit evaluation. Such scintigraphic examinations are of particular importance because clinical assessment of suspected functional gastrointestinal disorder frequently fails to accurately localize the site of disease, and those patients may have motility disorders involving multiple portions of the gastrointestinal tract. The authors comprehensively review the current practice of gastrointestinal transit scintigraphy, with diseases and best imaging practices illustrated by means of case review. ^©RSNA, 2024 See the invited commentary by Maurer and Parkman in this issue.

Viral pneumonia is usually community acquired and caused by influenza, parainfluenza, respiratory syncytial virus, human metapneumovirus, and adenovirus. Many of these infections are airway centric and chest imaging demonstrates bronchiolitis and bronchopneumonia, With the exception of adenovirus infections, the presence of lobar consolidation usually suggests bacterial coinfection. Community-acquired viral pathogens can cause more severe pneumonia in immunocompromised hosts, who are also susceptible to CMV and varicella infection. These latter 2 pathogens are less likely to manifest the striking airway-centric pattern. Airway-centric pattern is distinctly uncommon in Hantavirus pulmonary syndrome, a rare environmentally acquired infection with high mortality.

There is an increasing prevalence of non-communicable chronic diseases (NCCDs) like obesity, metabolic syndrome, type 2 diabetes mellitus (T2DM), hypertension, allergic asthma, and neuro-developmental/psychiatric problems in many parts of the world. A suboptimal lifestyle as an adult is often blamed for the occurrence of NCCDs. This review discusses the developmental origin of health and disease theory and how suboptimal nutrition in intrauterine life and the establishment of a suboptimal gut microbiome during infancy can influence the predisposition to NCCDs.