Pro- and anti-inflammatory cytokine associations with major depression in cancer patients.

OBJECTIVE: Cytokines may be linked to depression, although it has been challenging to demonstrate this association in cancer because of the overlap between depressive symptoms and other sickness behaviors. This study investigates the relationship between cytokines and depression in cancer patients, accounting for confounding clinical and methodological factors. METHODS: The GRID Hamilton Rating Scale for Depression and Neurotoxicity Rating Scale (NRS) for cytokine-induced sickness behaviors were administered to 61 cancer patients and 38 healthy controls. The cancer group was of mixed type and largely of late stage, with a recruitment rate of 35% and completion rate of 47%. Major depression was diagnosed in 19 of 61 (31%) cancer patients. Multiplexed cytokine assays for inflammatory and anti-inflammatory cytokines were conducted in plasma samples using electrochemiluminescence. RESULTS: All cancer patients had high NRS scores and elevated levels of most cytokines. Cancer patients with major depression had higher NRS scores than those without major depression. IL-1rα was positively associated with the GRID scores of depressive symptoms (regression coefficient, 3.52 ± 1.18; P = .004), but not with major depression. Major depression was negatively associated with the anti-inflammatory cytokine IL-4 (regression coefficient, -0.65 ± 0.26; P = .013), but not with IL-1rα. CONCLUSIONS: Depressive symptoms in cancer patients may represent sickness behaviors, which may have distinct cytokine associations from major depression. Sickness behaviors may be associated with an increase in inflammatory cytokines, whereas major depression may be induced by a failure to adequately resolve inflammation. Our findings suggest that cytokine-mediated interventions may be of value to treat depression in this population.

Functional Outcome After Poor-Grade Subarachnoid Hemorrhage: A Single-Center Study and Systematic Literature Review.

BACKGROUND AND PURPOSE: Poor-grade subarachnoid hemorrhage (SAH) (World Federation of Neurosurgical Societies grade 4 and 5) is associated with high mortality rates and unfavorable functional outcomes. We report a single-center cohort of poor-grade SAH patients, combined with a systematic review of studies reporting functional outcome in the poor-grade SAH population. METHODS: Data on a cohort of poor-grade SAH patients treated between 2009 and 2013 were retrospectively collected and combined with a systematic review (from inception to November 2015; PubMed, Embase). Two reviewers assessed the studies independently based on predefined inclusion criteria: consecutive poor-grade SAH, functional outcome measured at least 3 months after hemorrhage, and the report of patients who died before aneurysm treatment. RESULTS: The search yielded 329 publications, and 23 met our inclusion criteria with 2713 subjects enrolled from 1977 to 2014 in 10 countries (including 179 poor-grade patients from our cohort). Mortality rate was 60 % (1683 patients), of which 806 (29 %) died before and 877 (31 %) died after aneurysm treatment, respectively. Treatment was undertaken in 1775 patients (1775/2826-63 %): 1347 by surgical clipping (1347/1775-76 %) and 428 (428/1775-24 %) by endovascular methods. Outcome was favorable in 794 patients (28 %) and unfavorable in 1867 (66 %). When the studies were grouped into decades, favorable outcome increased from 13 % in the late 1970s to early 1980s to 35 % in the late 1980s to early 1990s, and remained unchanged thereafter. CONCLUSION: Although mortality remains high in poor-grade SAH patients, a favorable functional outcome can be achieved in approximately one-third of patients. The development of new diagnostic methods and implementation of therapeutic approaches were probably responsible for the decrease in mortality and improvement in the functional outcome from 1970 to the 1990s. The plateau in functional outcome seen thereafter might be explained by the treatment of sicker and older patients and by the lack of new therapeutic interventions specific for SAH.

The VASOGRADE: A Simple Grading Scale for Prediction of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Patients are classically at risk of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage. We validated a grading scale-the VASOGRADE-for prediction of DCI. METHODS: We used data of 3 phase II randomized clinical trials and a single hospital series to assess the relationship between the VASOGRADE and DCI. The VASOGRADE derived from previously published risk charts and consists of 3 categories: VASOGRADE-Green (modified Fisher scale 1 or 2 and World Federation of Neurosurgical Societies scale [WFNS] 1 or 2); VASOGRADE-Yellow (modified Fisher 3 or 4 and WFNS 1-3); and VASOGRADE-Red (WFNS 4 or 5, irrespective of modified Fisher grade). The relation between the VASOGRADE and DCI was assessed by logistic regression models. The predictive accuracy of the VASOGRADE was assessed by receiver operating characteristics curve and calibration plots. RESULTS: In a cohort of 746 patients, the VASOGRADE significantly predicted DCI (P<0.001). The VASOGRADE-Yellow had a tendency for increased risk for DCI (odds ratio [OR], 1.31; 95% CI, 0.77-2.23) when compared with VASOGRADE-Green; those with VASOGRADE-Red had a 3-fold higher risk of DCI (OR, 3.19; 95% CI, 2.07-4.50). Studies were not a significant confounding factor between the VASOGRADE and DCI. The VASOGRADE had an adequate discrimination for prediction of DCI (area under the receiver operating characteristics curve=0.63) and good calibration. CONCLUSIONS: The VASOGRADE results validated previously published risk charts in a large and diverse sample of subarachnoid hemorrhage patients, which allows DCI risk stratification on presentation after subarachnoid hemorrhage. It could help to select patients at high risk of DCI, as well as standardize treatment protocols and research studies.

Early CT perfusion changes and blood-brain barrier permeability after aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Early brain injury (EBI) can occur within 72 h of aneurysmal subarachnoid hemorrhage (aSAH). The objective of this study was to determine if there are differences in early CTP parameters (<72 h) with respect to delayed cerebral ischemia (DCI), cerebral infarction, and functional outcome. METHODS: We performed a prospective cohort study of aSAH patients admitted to a single tertiary care center. MTT, CBF and blood-brain barrier permeability (PS) were quantified with CTP within 72 h of aneurysm rupture. Primary outcomes were functional outcome by the Modified Rankin Scale (mRS) at 3 months and cerebral infarction. Secondary outcome was the development of DCI. Differences between early CTP parameters were determined with respect to primary and secondary outcomes. RESULTS: Fifty aSAH patients were included in the final analysis. MTT was significantly higher in patients who developed DCI (6.7 ± 1.2 vs 5.9 ± 1.0; p = 0.03) and cerebral infarction (7.0 ± 1.2 vs 5.9 ± 0.9; p = 0.007); however, no difference in MTT was found between patients with and without a poor outcome (mRS > 2). Early CBF and PS did not differ with respect to functional outcome, DCI, and cerebral infarction. CONCLUSIONS: Elevated MTT within 72 h of aneurysm rupture is associated with DCI and cerebral infarction but not with long-term functional outcome. Blood-brain barrier permeability, as assessed by CT perfusion, was not associated with DCI or worse outcome in this cohort.

Safety of early pharmacological thromboprophylaxis after subarachnoid hemorrhage.

OBJECTIVE: The recent guidelines on management of aneurysmal subarachnoid hemorrhage (aSAH) advise pharmacological thromboprophylaxis (PTP) after aneurysm obliteration. However, no study has addressed the safety of PTP in the aSAH population. Therefore, the aim of this study was to assess the safety of early PTP after aSAH. METHODS: Retrospective cohort of aSAH patients admitted between January 2012 and June 2013 in a single high-volume aSAH center. Traumatic SAH and perimesencephalic hemorrhage patients were excluded. Patients were grouped according to PTP timing: early PTP group (PTP within 24 hours of aneurysm treatment), and delayed PTP group (PTP started > 24 hours). RESULTS: A total of 174 SAH patients (mean age 56.3±12.5 years) were admitted during the study period. Thirty-nine patients (22%) did not receive PTP, whereas 135 patients (78%) received PTP after aneurysm treatment or negative angiography. Among the patients who received PTP, 65 (48%) had an external ventricular drain. Twenty-eight patients (21%) received early PTP, and 107 (79%) received delayed PTP. No patient in the early treatment group and three patients in the delayed PTP group developed an intracerebral hemorrhagic complication. Two required neurosurgical intervention and one died. These three patients were on concomitant PTP and dual antiplatelet therapy. CONCLUSIONS: The initiation of PTP within 24 hours may be safe after the treatment of a ruptured aneurysm or in angiogram-negative SAH patients with diffuse aneurysmal hemorrhage pattern. We suggest caution with concomitant use of PTP and dual antiplatelet agents, because it possibly increases the risk for intracerebral hemorrhage.

Bariatric Surgery Performed at a Tertiary Care Hospital and an Ambulatory Hospital: A 5 Year Comparison of Outcomes, OR Efficiencies and Costs.

PURPOSE: To explore change in 30-day post-operative complications, operative times, operating room (OR) efficiencies for bariatric surgery performed at a tertiary care hospital (TH) and an ambulatory hospital with overnight stay (AH) within one hospital network over 5 years; and to compare perioperative costs at the TH and AH. MATERIALS AND METHODS: We performed a retrospective analysis of existing data from a cohort of consecutive adult patients who underwent primary laparoscopic Roux-en-Y gastric bypass (LRYGB) and sleeve gastrectomy (LSG) between September 2016 and August 2021 at TH and AH. RESULTS: A total of 805 patients (762 LRYGB, 43 LSG) had surgery at AH, while 109 (92 LRYGB, 17 LSG) at TH. OR times for LRYGB and LSG performed at AH were significantly shorter versus TH (150 ± 24 vs 178 ± 51 min; p < 0.01) and (123 ± 24 vs 147 ± 34 min; p = 0.01). OR turnovers (19.2 ± 6.0 min vs 28.1 ± 6.1 min; p < 0.01) and Post Anesthetic Care Unit (PACU) times (2.4 ± 0.6 h vs 3.1 ± 1.5 h; p < 0.01) were significantly faster at AH versus TH. Proportion of patients requiring transfer for a complication from AH to TH remained constant over time (range 1.5-6.2%/year; p = 0.14). 30-day complication rates were similar between AH and TH (5.5-11% vs 0-15%; p = 0.12). LRYGB and LSG costs were similar between AH and TH (8,855 ± 1,328CAD vs 8,799 ± 2,729CAD; p = 0.91 and 8,763 ± 1,449CAD vs 7,857 ± 1,825CAD; p = 0.41). CONCLUSION: There was no difference in 30-day post-operative complications for LRYGB and LSG performed at AH and TH. Performing bariatric surgery at AH has the benefit of improved OR efficiency without a significant difference in total perioperative costs.

Exploring the Quality of Narrative Feedback Provided to Residents During Ambulatory Patient Care in Medicine and Surgery.

OBJECTIVES: The transition to competency-based medical education (CBME) has increased the volume of residents' assessment data; however, the quality of the narrative feedback is yet to be used as feedback-on-feedback for faculty. Our objectives were (1) to explore and compare the quality and content of narrative feedback provided to residents in medicine and surgery during ambulatory patient care and (2) to use the Deliberately Developmental Organization framework to identify strengths, weaknesses, and opportunities to improve quality of feedback within CBME. METHODS: We conducted a mixed convergent methods study with residents from the Departments of Surgery (DoS; n = 7) and Medicine (DoM; n = 9) at Queen's University. We used thematic analysis and the Quality of Assessment for Learning (QuAL) tool to analyze the content and quality of narrative feedback documented in entrustable professional activities (EPAs) assessments for ambulatory care. We also examined the association between the basis of assessment, time to provide feedback, and the quality of narrative feedback. RESULTS: Forty-one EPA assessments were included in the analysis. Three major themes arose from thematic analysis: Communication, Diagnostics/Management, and Next Steps. Quality of the narrative feedback varied; 46% had sufficient evidence about residents' performance; 39% provided a suggestion for improvement; and 11% provided a connection between the suggestion and the evidence. There were significant differences between DoM and DoS in quality of feedback scores for evidence (2.1 [1.3] vs. 1.3 [1.1]; p < 0.01) and connection (0.4 [0.5] vs. 0.1 [0.3]; p = 0.04) domains of the QuAL tool. Feedback quality was not associated with the basis of assessment or time taken to provide feedback. CONCLUSION: The quality of the narrative feedback provided to residents during ambulatory patient care was variable with the greatest gap in providing connections between suggestions and evidence about residents' performance. There is a need for ongoing faculty development to improve the quality of narrative feedback provided to residents.

Transitioning to virtual ambulatory care during the COVID-19 pandemic: a qualitative study of faculty and resident physician perspectives.

BACKGROUND: The COVID-19 pandemic resulted in a rapid shift from in-person to virtual care delivery for many medical specialties across Canada. The purpose of this study was to explore the lived experiences of resident physicians and faculty related to teaching, learning and assessment during ambulatory virtual care encounters within the competency-based medical education model. METHODS: In this qualitative phenomenological study, we recruited resident physicians (postgraduate year [PGY] 1-5 trainees) and faculty from the Departments of Surgery and Medicine at Queen's University, Ontario, via purposive sampling. Participants were not required to have exposure to virtual care. Interviews were conducted from September 2020 to March 2021 by 1 researcher, and 2 researchers conducted focus groups via Zoom to explore participants' experiences with the transition to virtual care. These were audio-recorded and transcribed verbatim; qualitative data were analyzed thematically. RESULTS: There were 18 male and 19 female participants; 20 were resident physicians and 17 were faculty; 19 were from the Department of Surgery and 18 from the Department of Medicine. All faculty participants had participated in virtual care during ambulatory care; 2 PGY-1 residents in surgery had not actively participated in virtual care, although they had participated in clinics where faculty were using virtual care. The mean age of faculty participants was 38 (standard deviation [SD] 8.6) years, and the mean age of resident physicians was 29 (SD 5.4) years. Overall, 28 interviews and 4 focus groups (range 2-3 participants per group) were conducted, and 4 themes emerged: teaching and learning, assessment, logistical considerations, and suggestions. Barriers to teaching included the lack of direct observations and teaching time, and barriers to assessment included an absence of specific Entrustable Professional Activities (EPAs) and feedback focused on virtual care-related competencies. Logistical challenges included lack of technological infrastructure, insufficient private office space and administrative burdens. Both resident physicians and faculty did not foresee virtual care limiting resident physicians' ability to progress within competency-based medical education. Benefits of virtual care included increased accessibility to patients for follow-up visits, for disclosing patients' results and for out-of-town visits. Suggestions included faculty development, improved access to technology and space, educational guidelines for conducting virtual care encounters, and development of virtual care-specific competencies and EPAs. INTERPRETATION: In the postgraduate program we studied, virtual care imposed substantial barriers on teaching, learning and assessment during the first year of the COVID-19 pandemic. Adapting to new circumstances such as virtual care with suggestions from resident physicians and faculty may help to ensure the continuity of postgraduate medical education throughout the COVID-19 pandemic.

An Evaluation of the Surgical Foundations Curriculum: A National Study.

BACKGROUND: Canadian Surgical Foundations (SF) residency programs transitioned to competency-based medical education in 2018. It is unknown how well the SF curriculum prepares surgery residents to recognize and manage common perioperative patient presentations. We sought to evaluate the national SF curriculum using the Kirkpatrick model of curriculum evaluation. METHODS: We administered online surveys to 300 first-year English-speaking surgery residents across Canada to assess self-reported confidence in recognizing and managing 7 common perioperative patient presentations at 3 timepoints: pre-SF (July 2019), mid-SF (December 2019), and post-SF (May 2020). We conducted multistation simulation-based objective structured clinical examinations for surgery residents at our institution pre-SF (August 2019) and mid-SF (December 2019), and collected workplace-based assessment (WBA) data, including entrustment scores and narrative feedback, for 6 preselected entrustable professional activities (EPAs) (July 2019 to May 2020). RESULTS: Fifty-five residents (18%) completed pre-SF, 31 (10%) completed mid-SF, and 52 (17%) completed post-SF surveys. Residents' confidence in recognizing 6 out of 7 patient presentations was high pre-SF and did not improve significantly during the SF curriculum except for recognizing poor glycemic control (p < 0.01). Residents' confidence in managing 7 out of 7 patient presentations improved significantly (p < 0.05). Objective structured clinical examinations performance did not change significantly between pre-SF and mid-SF (4 [3.5-4.5] vs 4 [3-4]; p = 0.28). Analysis of WBA data showed that residents received high entrustment scores from the start of the SF curriculum. Entrustment scores improved significantly during the SF curriculum for 2 out of 6 EPAs. Only 56% of WBA assessments had narrative feedback, 16% of which had somewhat constructive feedback. CONCLUSION: Participation in the SF curriculum was associated with improved confidence of surgery residents in managing common perioperative patient presentations, and greater level of entrustment for some EPAs. Consideration should be given to further faculty development to increase the quantity and quality of narrative feedback in the SF curriculum.

Cytokines and depression in cancer patients and caregivers.

OBJECTIVE: A better understanding of the biobehavioral mechanisms underlying depression in cancer is required to translate biomarker findings into clinical interventions. We tested for associations between cytokines and the somatic and psychological symptoms of depression in cancer patients and their healthy caregivers. PATIENTS AND METHODS: The GRID Hamilton Rating Scale for Depression (Ham-D) was administered to 61 cancer patients of mixed type and stage, 26 primary caregivers and 38 healthy controls. Concurrently, blood was drawn for multiplexed plasma assays of 15 cytokines. Multiple linear regression, adjusted for biobehavioral variables, identified cytokine associations with the psychological (Ham-Dep) and somatic (Ham-Som) subfactors of the Ham-D. RESULTS: The Ham-Dep scores of cancer patients were similar to their caregivers, but their Ham-Som scores were significantly higher (twofold, p=0.016). Ham-Som was positively associated with IL-1ra (coefficient: 1.27, p≤0.001) in cancer patients, and negatively associated with IL-2 (coefficient: -0.68, p=0.018) in caregivers. Ham-Dep was negatively associated with IL-4 (coefficient: -0.67, p=0.004) in cancer patients and negatively associated with IL-17 (coefficient: -1.81, p=0.002) in caregivers. CONCLUSION: The differential severity of somatic symptoms of depression in cancer patients and caregivers and the unique cytokine associations identified with each group suggests the potential for targeted interventions based on phenomenology and biology. The clinical implication is that depressive symptoms in cancer patients can arise from biological stressors, which is an important message to help destigmatize the development of depression in cancer patients.