Critical Care: What You May Have Missed in 2023.

Critical care medicine is a specialty that brings together a truly wide spectrum of patient populations, disease states, and treatment methods. This article highlights 10 important pieces of research from 2023 (and 1 from 2022) in critical care. The literature was screened for new evidence relevant to internal medicine physicians and hospitalists whose focus of practice is not critical care but who may be taking care of seriously ill patients. The articles highlight the diverse spectrum of pathology and interplay of various specialties that go into critical care. Topics include transfusion medicine, fluid resuscitation, safe intubation practices and respiratory failure, and the management of acute ischemic stroke. Several trials are groundbreaking, forcing clinicians to reconsider preexisting dogma and likely adopt new treatment strategies.

Exercising medical judgement: resuscitation and "Decision-Making for End-of-Life Care," a new policy from the College of Physician and Surgeons of Ontario.

In March 2023, the College of Physicians and Surgeons of Ontario (CPSO) updated their policy entitled Decision-Making for End-of-Life Care. This policy will significantly change the landscape and clinical practice in Canada's most populous province with respect to decision-making for resuscitation. The update interrupts approximately eight years of CPSO policy that has mandated physicians to perform cardiopulmonary resuscitation (CPR) and other resuscitative measures unless they can explicitly obtain consent in the form of a do-not-resuscitate or no-CPR order. The policy is now aligned with the Wawrzyniak v. Livingstone, 2019 court decision which reaffirmed that physicians must only offer treatments that they think are within the standard of care and not offer treatments that are not likely to benefit their patient. In this commentary, we review the historical aspects of the CPSO policy from 2015 to 2023 and discuss how such a policy of a "consent to withhold" paradigm was ethically problematic and likely led to significant harm. We then review the updated CPSO policy, outline some remaining areas of uncertainty and challenges, and make recommendations for how to interpret this policy in clinical practice.

RéSUMé: En mars 2023, l'Ordre des médecins et chirurgiens de l'Ontario (OMCO) a mis à jour sa politique intitulée Prise de décision pour les soins de fin de vie. Cette politique changera considérablement le paysage et la pratique clinique dans la province la plus peuplée du Canada en ce qui concerne la prise de décision en matière de réanimation. Cette mise à jour met fin à environ huit ans de politique de l'OMCO qui mandatait les médecins de procéder à la réanimation cardiorespiratoire (RCR) et de pratiquer d'autres mesures de réanimation, à moins d'avoir explicitement obtenu le consentement sous la forme d'une ordonnance de non-réanimation ou d'interdiction de RCR. La politique s'aligne maintenant sur la décision de la Cour dans Wawrzyniak c. Livingstone, 2019, qui a réaffirmé que les médecins ne doivent offrir que des traitements jugés conformes à la norme de soins et ne doivent pas offrir de traitements qui ne sont pas susceptibles d'être bénéfiques pour leur patient·e. Dans ce commentaire, nous passons en revue les aspects historiques de la politique de l'OMCO de 2015 à 2023 et discutons de la façon dont une telle politique fondée sur un paradigme de « consentement à retenir les soins ¼ était problématique sur le plan éthique et a probablement entraîné un préjudice important. Nous passons ensuite en revue la politique mise à jour de l'OMCO, décrivons certains domaines d'incertitude et de défis qui subsistent, et formulons des recommandations sur la façon d'interpréter cette politique dans la pratique clinique.

The Next Surgical Skills and Technology Elective Program: The "Surgical Skills and Technology Elective Program" Decreases Cognitive Load During Suturing Tasks in Second Year Medical Students.

OBJECTIVE: The Surgical Skills and Technology Elective Program (SSTEP) is a one-week, simulation-based procedural skills bootcamp for preclinical medical students. Using cognitive load (CL) as a useful framework for understanding simulation in medical education, our aims were to (1) examine the ability of SSTEP to decrease medical students' CL during procedural skills training and (2) determine the impact of SSTEP on secondary learning. METHODS: In this prospective cohort study, twenty SSTEP participants and twenty controls were recruited. CL was assessed during a simple suturing task and a clinical vignette multitasking activity, where participants were required to suture and concurrently listen to a clinical vignette. CL was measured using the validated Subjective Rating of Mental Effort (SRME) and its impact on working memory was assessed using a knowledge test about the clinical vignette. RESULTS: Participants reported lower SRME scores while suturing following SSTEP, which persisted at 3 months (p = 0.002) and were significantly lower than controls (p = 0.031). Participants also reported lower SRME scores during the clinical vignette multitasking activity (p = 0.011), despite no improvement among controls (p = 0.63). Participants significantly outperformed controls on the clinical vignette knowledge test (p = 0.02). CONCLUSIONS: Surgical skills training through SSTEP was associated with lower reports of mental effort and increased performance on secondary learning tasks. Procedural skills bootcamps may better prepare students for the complex learning environments encountered during clinical clerkship.

Murine Joubert syndrome reveals Hedgehog signaling defects as a potential therapeutic target for nephronophthisis.

Nephronophthisis (NPHP) is the major cause of pediatric renal failure, yet the disease remains poorly understood, partly due to the lack of appropriate animal models. Joubert syndrome (JBTS) is an inherited ciliopathy giving rise to NPHP with cerebellar vermis aplasia and retinal degeneration. Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion. We present a Cep290 gene trap mouse model of JBTS that displays the kidney, eye, and brain abnormalities that define the syndrome. Mutant mice present with cystic kidney disease as neonates. Newborn kidneys contain normal amounts of lymphoid enhancer-binding factor 1 (Lef1) and transcription factor 1 (Tcf1) protein, indicating normal function of the Wnt signaling pathway; however, an increase in the protein Gli3 repressor reveals abnormal Hedgehog (Hh) signaling evident in newborn kidneys. Collecting duct cells from mutant mice have abnormal primary cilia and are unable to form spheroid structures in vitro. Treatment of mutant cells with the Hh agonist purmorphamine restored normal spheroid formation. Renal epithelial cells from a JBTS patient with CEP290 mutations showed similar impairments to spheroid formation that could also be partially rescued by exogenous stimulation of Hh signaling. These data implicate abnormal Hh signaling as the cause of NPHP and suggest that Hh agonists may be exploited therapeutically.

Trauma in the Aging Population: Geriatric Trauma Pearls.

The relative proportion of trauma patients who are older adults continues to rise as the population ages. Older adults who experience trauma have unique needs compared with their younger counterparts. There are specific considerations that must take into account. Treating older adults with traumatic injuries requires specific skills, knowledge, and specialized protocols to optimize outcomes. This article reviews the most important aspects of geriatric trauma care. We focus on presentation and initial resuscitation, triage guidelines and the issue of undertriage, the importance of multidisciplinary and specialized geriatric care, and common injuries and their management.

Recommendation-making in the emergency department: A qualitative study of how Canadian emergency physicians guide treatment decisions about resuscitation in critically ill patients.

Study Objective: Emergency physicians are frequently responsible for making time-sensitive decisions around the provision of life-sustaining treatment. These decisions can involve goals of care or code status discussion, which will often substantially alter a patient's care pathway. A central part of these conversations that has received relatively little attention are recommendations for care. By proposing a best course of action or treatment via a recommendation, a clinician can ensure that their patients receive care that is concordant with their values. The objective of this study is to explore emergency physicians' attitudes toward recommendations about resuscitation in critically ill patients in the emergency department (ED). Methods: We recruited Canadian emergency physicians via multiple recruitment strategies to ensure maximum variation sampling. Semi-structured qualitative interviews were conducted until thematic saturation occurred. Participants were asked about their perspectives and experiences with respect to recommendation-making in critically ill patients and to identify areas for improvement in this process in the ED. We used a qualitative descriptive approach and thematic analysis to identify themes around recommendation-making in the ED for critically ill patients. Results: Sixteen emergency physicians agreed to participate. We identified four themes and multiple subthemes. Major themes included identification of the roles and responsibilities of the emergency physician (EP) with respect to making a recommendation, the logistics or process of making a recommendation, barriers to making a recommendation, and how to improve recommendation-making and goals of care conversations in the ED. Conclusion: Emergency physicians provided a range of perspectives on the role of recommendation-making in critically ill patients in the ED. Several barriers to the inclusion of a recommendation were identified and many physicians provided ideas on how to improve goals of care conversations, the recommendation-making process, and ensure that critically ill patients receive care that is concordant with their values.

Objective Structured Assessment of technical skill (OSATS) in the Surgical Skills and Technology Elective Program (SSTEP): Comparison of peer and expert raters.

BACKGROUND: A major challenge with Competency Based Medical Education (CBME) is that of increased assessment burden on faculty. To reduce this burden, the accuracy and reliability of peer-assessment for surgical skills requires further exploration. METHODS: Forty-two second year medical students were video recorded while performing a simple interrupted suture and an instrument tie. Four novice raters underwent a short training session on the use of the Objective Structured Assessment of Technical Skills (OSATS) checklists. Videos of the suturing task were then independently assessed by the four novice raters and two expert raters on two occasions. Agreement between novice and expert rater scores was calculated using the intraclass correlation coefficient (ICC). RESULTS: For both simple interrupted suturing (ICC = 0.78, CI = 0.66-0.86, p < 0.001) and instrument ties (ICC = 0.87, CI = 0.80-0.92, p < 0.001), there was good agreement between novice and expert raters. CONCLUSIONS: Novice raters can be taught to use the OSATS checklists to assess peers on simple suturing and instrument tying tasks.

Identification of tumor size as the only factor associated with nondiagnostic biopsies in patients with small renal masses.

INTRODUCTION: As greater numbers of small renal masses (SRMs) are discovered incidentally, renal tumor biopsy (RTB) is an increasingly recognized step for the management of these lesions, ideally for the prevention of surgical overtreatment for benign disease. While the diagnosis can often be obtained preoperatively by RTB, indeterminate results create greater difficulty for patients and clinicians. This study examines a series of RTBs, identifying the portion of these that were able to yield a diagnosis, and correlates patient factors, including RENAL and PADUA scoring, with the outcome of a non-diagnostic result. METHODS: Patients were identified as having undergone RTB at the Princess Margaret Cancer Centre in Ontario, Canada, between January 2000 and December 2009. Data was compiled from these 423 patients and analyzed using CART methodology to determine the level of association between various patient and tumor factors and the outcome of a non-diagnostic biopsy. Tumor size was further used to develop a classification tree to describe the prediction of a non-diagnostic biopsy. RESULTS: Of these 423 patients undergoing RTB, 66 (16%) resulted in a non-diagnostic biopsy. The only patient or tumor factor that was found to be associated with a non-diagnostic outcome was mass size, where small masses (<1.28 cm diameter) were found to have a 38% chance of being non-diagnostic, compared with a 13% chance in those tumors >1.28 cm diameter (86% accuracy, 95% confidence interval [CI] 0.82-0.89). CONCLUSIONS: When evaluating SRMs for diagnostic workup, mass size is the only tumor or patient characteristic associated with a non-diagnostic RTB.

Classification tree for the prediction of malignant disease and the prediction of non-diagnostic biopsies in patients with small renal masses.

INTRODUCTION: Preoperative prediction of benign vs. malignant small renal masses (SRMs) remains a challenge. This study: 1) validates our previously published classification tree (CT) with an external cohort; 2) creates a new CT with the combined cohort; and 3) evaluates the RENAL and PADUA scoring systems for prediction of malignancy. METHODS: This study includes a total of 818 patients with renal masses; 395 underwent surgical resection and 423 underwent biopsy. A CT to predict benign disease was developed using patient and tumour characteristics from the 709 eligible participants. Our CT is based on four parameters: tumour volume, symptoms, gender, and symptomatology. CART modelling was also used to determine if RENAL and PADUA scoring could predict malignancy. RESULTS: When externally validated with the surgical cohort, the predictive accuracy of the old CT dropped. However, by combining the cohorts and creating a new CT, the predictive accuracy increased from 74% to 87% (95% confidence interval 0.84-0.89). RENAL and PADUA score alone were not predictive of malignancy. One limitation was the lack of available histological data from the biopsy series. CONCLUSIONS: The validated old CT and new combined-cohort CT have a predictive value greater than currently published nomograms and single-biopsy cohorts. Overall, RENAL and PADUA scores were not able to predict malignancy.

A "Neurological Emergency Trolley" reduces turnaround time for high-risk medications in a general intensive care unit.

OBJECTIVES: To reduce medication turnaround times during neurological emergencies, a multidisciplinary team developed a neurological emergency crash trolley in our intensive care unit. This trolley includes phenytoin, hypertonic saline and mannitol, as well as other equipment. The aim of this study was to assess whether the cart reduced turnaround times for these medications. RESEARCH METHODOLOGY/DESIGN: In this retrospective cohort study, medication delivery times for two year epochs before and after its implementation were compared. Eligible patients were identified from our intensive care unit screening log. Adults who required emergent use of phenytoin, hypertonic saline or mannitol while in the intensive care unit were included. Groups were compared with nonparametric analyses. SETTING: 33-bed general medical-surgical intensive care unit in an academic teaching hospital. MAIN OUTCOME MEASURES: Time to medication administration. RESULTS: In the pre-intervention group, there were 43 patients with 66 events. In the post-intervention group, there were 45 patients with 80 events. The median medication turnaround time was significantly reduced after implementation of the neurological emergency trolley (25 vs. 10minutes, p=0.003). There was no statistically significant difference in intensive care or 30-day survival between the two cohorts. CONCLUSION: The implementation of a novel neurological emergency crash trolley in our intensive care unit reduced medication turnaround times.

The von Hippel-Lindau Gene Is Required to Maintain Renal Proximal Tubule and Glomerulus Integrity in Zebrafish Larvae.

BACKGROUND: von Hippel-Lindau (VHL) disease is characterized by the development of benign and malignant tumours in many organ systems, including renal cysts and clear cell renal cell carcinoma. It is not completely understood what underlies the development of renal pathology, and the use of murine Vhl models has been challenging due to limitations in disease conservation. We previously described a zebrafish model bearing inactivating mutations in the orthologue of the human VHL gene. METHODS: We used histopathological and functional assays to investigate the pronephric and glomerular developmental defects in vhl mutant zebrafish, supported by human cell culture assays. RESULTS: Here, we report that vhl is required to maintain pronephric tubule and glomerulus integrity in zebrafish embryos. vhl mutant glomeruli are enlarged, cxcr4a+ capillary loops are dilated and the Bowman space is widened. While we did not observe pronephric cysts, the cells of the proximal convoluted and anterior proximal straight tubule are enlarged, periodic acid schiff (PAS) and Oil Red O positive, and display a clear cytoplasm after hematoxylin and eosine staining. Ultrastructural analysis showed the vhl-/- tubule to accumulate large numbers of vesicles of variable size and electron density. Microinjection of the endocytic fluorescent marker AM1-43 in zebrafish embryos revealed an accumulation of endocytic vesicles in the vhl mutant pronephric tubule, which we can recapitulate in human cells lacking VHL. CONCLUSIONS: Our data indicates that vhl is required to maintain pronephric tubule and glomerulus integrity during zebrafish development, and suggests a role for VHL in endocytic vesicle trafficking.

Non-invasive sources of cells with primary cilia from pediatric and adult patients.

BACKGROUND: Ciliopathies give rise to a multitude of organ-specific pathologies; obtaining relevant primary patient material is useful for both diagnostics and research. However, acquisition of primary ciliated cells from patients, particularly pediatric patients, presents multiple difficulties. Biopsies and blood samples are invasive, and patients (and their parents) may be reluctant to travel to medical centers, especially for research purposes. We sought to develop non-invasive methods of obtaining viable and ciliated primary cells from ciliopathy patients which could be obtained in the home environment. FINDINGS: We introduce two methods for the non-invasive acquisition of primary ciliated cells. In one approach, we collected spontaneously shed deciduous (milk) teeth from children. Fibroblast-like cells were observed after approximately 2 weeks of culture of fragmented teeth. Secondly, urine samples were collected from children or adults. Cellular content was isolated and after approximately 1 week, renal epithelial cells were observed. Both urine and tooth-derived cells ciliate and express ciliary proteins visible with immunofluorescence. Urine-derived renal epithelial cells (URECs) are amenable to 3D culturing, siRNA knockdown, and ex vivo drug testing. CONCLUSIONS: As evidence continues to accumulate showing that the primary cilium has a central role in development and disease, the need for readily available and ciliated patient cells will increase. Here, we introduce two methods for the non-invasive acquisition of cells with primary cilia. We believe that these cells can be used for further ex vivo study of ciliopathies and in the future, for personalized medicine.

3D spheroid model of mIMCD3 cells for studying ciliopathies and renal epithelial disorders.

We have developed a novel 3D cell culture model that uses mouse inner-medullary collecting duct (mIMCD3) cells to generate epithelial spheroids. This model is amenable to efficient siRNA knockdown and subsequent rescue with human patient-derived alleles. Spheroids develop apicobasal polarity and complete lumens, and they are consequently an ideal model for polarity defects seen in renal ciliopathies such as nephronophthisis. Briefly, mIMCD3 cells are transfected and subsequently passaged to a Matrigel mixture, which is seeded in chamber slides and covered in growth medium. Once the spheroids are formed, Matrigel is dissolved and immunocytochemistry is performed in the chamber slides. The technique is amenable to semiautomatic imaging analysis, and it can test multiple genes simultaneously, gene-dosing effects and a variety of therapeutic interventions. The spheroid technique is a unique and simple 6-d in vitro method of interrogating ex vivo tissue organization.