Optimizing Informed Consent Discussions: Developing a Narrative for Transfusion Consent.

Ensuring patient informed consent is a key tenet of modern medicine. Although transfusion of blood products is among the most common medical procedures performed in hospitalized patients, there is evidence that informed consent for transfusion is at times incomplete, poorly understood, hurried, and/or inaccurate. This study aimed to develop a narrative that can be used as a framework for practicing physicians and for educational purposes to optimize the process for obtaining informed consent for blood transfusion. The narrative was developed using a modified Delphi approach with 5 Rounds that included feedback from transfusion medicine (TM) experts, transfusion-provider physicians, and lay people. The surveys collected qualitative and quantitative data analyzed using thematic content analysis and descriptive statistics, respectively. Results from Rounds 1 and 2 generated a draft narrative and Rounds 3 to 5 informed further modifications. Round 1 included draft narrative scripts from 28 TM experts; thematic coding generated 97 topics. In round 2, 22/28 of the initial experts rated items identified from Round 1. Those with a content validity index (CVI) ≥ 0.8 were used by the authors to develop a narrative. In Round 3, 20/24 participants from Round 2 reviewed the narrative with 100% agreeing on the items included and 90% agreeing the flow was logical. In Round 4, 23 transfusion prescribers (non-TM physicians) reviewed the narrative for flow, manner, length, and usability; there was 83% agreement with the nonexclusion of important topics; 91% felt it would be effective for teaching trainees. Round 5 included 24 nonmedical laypeople of different demographics. Most participants (92%) thought that the script was appropriate in length and there were opportunities to ask questions. Participants could also identify the adverse transfusion reactions and understand that they could refuse the transfusion. A narrative for obtaining informed consent for blood transfusion was created through multiple rigorous iterations of review and feedback with both transfusion providers and the lay public. The narrative, developed for a specific clinical scenario, was well-received by medical and nonmedical participants and can be used, and modified, to help ensure patients understand the risks and benefits of blood transfusion.

Convalescent plasma therapy for coronavirus disease 2019 in ambulatory versus hospitalized patients: Efficacy and risk of thromboembolism.

Background: Although early evidence concluded a lack of clinical benefit of convalescent plasma therapy (CPT) in COVID-19 management, recent trials have demonstrated the therapeutic potential of CPT in ambulatory care. CPT may also potentiate thromboembolic events, given the presence of coagulation factors and the prothrombotic state of COVID-19. Objectives: The present study aimed to assess and compare the clinical efficacy and the risk of venous thromboembolism (VTE)/arterial thromboembolism (ATE) of CPT in ambulatory versus hospitalized patients with COVID-19. Methods: MEDLINE, Embase, and Cochrane CENTRAL were searched from December 2019 to December 2022 for randomized controlled trials that investigated the use of CPT against placebo or standard of care in adult patients with COVID-19. The primary outcome was nonmortality disease progression. Secondary outcomes include VTE, ATE, 28-day mortality, clinical improvement, length of hospitalization, sepsis/fever, and major adverse cardiovascular events. Results: Twenty randomized controlled trials, with 21,340 patients, were included. CPT significantly reduced nonmortality disease progression in ambulatory patients (odds ratio [OR], 0.72; 95% CI, 0.56-0.92; P = .009) but not in hospitalized patients (OR, 1.03; 95% CI, 0.94-1.12; P = .58). The risk of VTE and ATE did not differ between the CPT and the control group (OR, 1.16; 95% CI, 0.82-1.66; P = .40; and OR, 1.01; 95% CI, 0.37-2.79; P = .98, respectively). No conclusive differences between CPT and control groups were noted in 28-day mortality, clinical improvement, length of hospitalization, risk of sepsis/fever, and major adverse cardiovascular events. Conclusion: In conclusion, treatment of COVID-19 with CPT prevents the progression of COVID-19 in the ambulatory care. It is not associated with an increased risk of VTE, ATE, or other adverse events.

How do I provide rare red cells to patients?

BACKGROUND: The demand for rare blood is expected to increase in Canada as its population continues to expand through immigration from diverse regions of the world. MATERIAL AND METHODS: This paper outlines a national approach to providing rare red cells for patients through the Rare Blood Program of Canadian Blood Services (CBS). Data detailing the rare red cell requests and inventory managed by CBS' Rare Blood Program is provided. RESULTS: The provision of rare red cells involves multiple considerations such as multidisciplinary communication, serologic/molecular confirmation, donor recruitment, inventory optimization and logistical factors. CONCLUSION: The description of CBS' Rare Blood Program will inform others that seek to create, optimize, or expand programs that facilitate the provision of rare blood. New technologies such as next-generation sequencing may also affect how rare donors are identified and recruited in the future.

Combined preoperative plasma exchange and red blood cell exchange transfusion in a renal transplant patient with protein S deficiency and hemoglobin SC disease.

BACKGROUND: Protein S deficiency is associated with increased risk of venous thromboembolism, complicating the perioperative management of such patients. We present a patient with sickle cell disease (Hb SC genotype) and inherited protein S deficiency who underwent a living-donor renal transplant. To minimize thrombotic risk and sickle cell complications, both plasma exchange and red blood cell (RBC) exchange transfusion were performed pre-operatively. METHODS AND MATERIALS: Plasma exchange was utilized to increase protein S levels and to reduce the risk of post-operative venous thromboembolism, including allograft thrombosis, while RBC exchange was performed to reduce the risk of acute post-operative sickle cell disease complications. RESULTS: With the use of combined pre-operative plasma exchange and RBC exchange transfusion, this patient with protein S deficiency and Hb SC underwent a successful renal transplant without acute sickle cell complications or thrombotic complications. CONCLUSIONS: This case demonstrates the potential use of pre-operative plasma exchange in patients with protein S deficiency undergoing high thrombotic risk procedures.

Improving Medical Education in Hematology and Transfusion Medicine in Canada: Standards and Limitations.

The paradigm of medical education is evolving with the introduction of competency-based medical education (CBME) and it is crucial that residency programs adapt. In this paper, we provide an overview of the current status of medical education in Hematology in Canada including models of training, assessment methods, anticipated challenges, and the effects of the COVID-19 pandemic. We will also discuss additional training that can be pursued after a Hematology residency, with a particular focus On Transfusion Medicine as it was one of the first programs to implement a competency-based curriculum. Finally, we explore the future directions of medical education in Hematology and Transfusion Medicine.

Teaching bone marrow procedures at pelvic and sternal sites: a high fidelity anatomy simulation.

The bone marrow aspirate and biopsy procedure are fundamental to the diagnosis of many hematologic pathologies. We describe a hands-on, anatomy-based workshop that allows learners to practice bone marrow procedures on cadavers. Notably, participants learned how to perform sternal aspirates: a procedure rarely performed in real-life practice. Learners valued the experience and described increased comfort with the procedure after the workshop. This workshop provides a valuable opportunity for trainees to learn a procedural skill in a safe, high fidelity environment. Given its hands-on nature, residency training programs could also adapt it for direct observation and trainee assessment.

La ponction et la biopsie de la moelle osseuse sont d'une importance capitale pour le diagnostic de nombreuses pathologies hématologiques. Nous décrivons un atelier pratique, axé sur l'anatomie, qui permet aux apprenants de faire des prélèvements de moelle osseuse sur des cadavres. Les participants ont notamment appris à effectuer des ponctions sternales, une intervention qui est plutôt rare dans la pratique réelle. Ils indiquent avoir apprécié l'atelier, grâce auquel ils ont pris confiance pour pratiquer la technique. L'atelier est une occasion précieuse pour les apprenants d'acquérir une habileté technique dans un environnement sûr et haute fidélité. Étant donné son caractère pratique, les programmes de résidence pourraient aussi l'adapter dans un contexte d'observation directe et d'évaluation.

Frequency of arterial thromboembolism in populations with malignancies: A systematic review.

BACKGROUND: Populations with cancer have been documented to have a greater risk of developing venous thromboembolism. The frequency of arterial thromboembolism (ATE) in cancer patients is unclear; while evidence examining this question has grown, it has yet to be systematically summarized. This study aims to systematically review the frequency of ATE in patients with cancer. METHODS: A search of MEDLINE, Embase, CENTRAL, and Web of Science from inception to 28 January, 2019 was conducted. Two independent reviewers screened for eligible studies. Studies comparing the frequency of ATE between populations with cancer and controls were included while studies examining the frequency of ATE in the context of cancer therapies (e.g., chemotherapy, radiotherapy) were excluded. Data corresponding to the follow-up times closest to diagnosis and 1-year follow-up were extracted. Results Twelve retrospective cohort studies involving 1,260,237 patients were included. Ten studies concluded increased ATE risk in populations with malignancies. At the time point closest to diagnosis, patients with bladder, breast, colorectal, gastric, lung, non-Hodgkin lymphoma, and pancreatic cancers were at an increased risk. This risk diminished around 1 year after diagnosis except in patients with lung or pancreatic cancers. High heterogeneity within and between studies precluded meta-analysis. CONCLUSIONS: Patients with cancer appear to have an increased risk of developing ATE, with the highest risk immediately after diagnosis and in patients with lung and pancreatic cancers. Better information on the attribu01 risk will require prospective studies that record comprehensive patient characteristics and interventions.

Targeted metabolomics in colorectal cancer: a strategic approach using standardized laboratory tests of the blood and urine.

BACKGROUND: Glycolytic markers have been detected in colorectal cancer (CRC) using advanced analytical methods. METHODS: Using commercially available assays, by-products of anaerobic metabolism were prospectively measured in the blood and urine of 20 patients with metastatic colorectal cancer (mCRC) and 20 patients with local disease. Twenty-four-hour urine citrate, plasma lactate, ketones, venous blood gas, anion gap, and osmolar gap were investigated. Results of patients with metastatic and local CRC were compared using two-sample t-tests or equivalent nonparametric tests. In addition, plasma total CO2 concentrations in our local hospital (5,931 inpatients and 1,783 outpatients) were compared retrospectively with those in our dedicated cancer center (1,825 outpatients) over 1 year. RESULTS: The average venous pCO2 was higher in patients with mCRC (50.2 mmHg; standard deviation [SD]=9.36) compared with those with local disease (42.8 mmHg; SD=8.98), p=0.045. Calculated serum osmolarity was higher in mCRC and attributed to concomitant sodium and urea elevations. In our retrospective analysis, plasma total CO2 concentrations (median=27 mmol/L) were higher in cancer patients compared to both hospital inpatients (median=23 mmol/L) and outpatients (median=24 mmol/L), p<0.0001. CONCLUSION: Patients with mCRC had higher venous pCO2 levels than those with local disease. Although causation cannot be established, we hypothesize that pCO2 elevation may stem from a perturbed metabolism in mCRC.

Integrated omic analysis of oropharyngeal carcinomas reveals human papillomavirus (HPV)-dependent regulation of the activator protein 1 (AP-1) pathway.

HPV-positive oropharyngeal carcinoma (OPC) patients have superior outcomes relative to HPV-negative patients, but the underlying mechanisms remain poorly understood. We conducted a proteomic investigation of HPV-positive (n = 27) and HPV-negative (n = 26) formalin-fixed paraffin-embedded OPC biopsies to acquire insights into the biological pathways that correlate with clinical behavior. Among the 2,633 proteins identified, 174 were differentially abundant. These were enriched for proteins related to cell cycle, DNA replication, apoptosis, and immune response. The differential abundances of cortactin and methylthioadenosine phosphorylase were validated by immunohistochemistry in an independent cohort of 29 OPC samples (p = 0.023 and p = 0.009, respectively). An additional 1,124 proteins were independently corroborated through comparison to a published proteomic dataset of OPC. Furthermore, utilizing the Cancer Genome Atlas, we conducted an integrated investigation of OPC, attributing mechanisms underlying differential protein abundances to alterations in mutation, copy number, methylation, and mRNA profiles. A key finding of this integration was the identification of elevated cortactin oncoprotein levels in HPV-negative OPCs. These proteins might contribute to reduced survival in these patients via their established role in radiation resistance. Through interrogation of Cancer Genome Atlas data, we demonstrated that activation of the ß1-integrin/FAK/cortactin/JNK1 signaling axis and associated differential regulation of activator protein 1 transcription factor target genes are plausible consequences of elevated cortactin protein levels.

Abnormal protein turnover and anabolic resistance to exercise in sarcopenic obesity.

Obesity may impair protein synthesis rates and cause anabolic resistance to growth factors, hormones, and exercise, ultimately affecting skeletal muscle mass and function. To better understand muscle wasting and anabolic resistance with obesity, we assessed protein 24-h fractional synthesis rates (24-h FSRs) in selected hind-limb muscles of sedentary and resistance-exercised lean and obese Zucker rats. Despite atrophied hind-limb muscles (-28% vs. lean rats), 24-h FSRs of mixed proteins were significantly higher in quadriceps (+18%) and red or white gastrocnemius (+22 or +38%, respectively) of obese animals when compared to lean littermates. Basal synthesis rates of myofibrillar (+8%) and mitochondrial proteins (-1%) in quadriceps were not different between phenotypes, while manufacture of cytosolic proteins (+12%) was moderately elevated in obese cohorts. Western blot analyses revealed a robust activation of p70S6k (+178%) and a lower expression of the endogenous mTOR inhibitor DEPTOR (-28%) in obese rats, collectively suggesting that there is an obesity-induced increase in net protein turnover favoring degradation. Lastly, the protein synthetic response to exercise of mixed (-7%), myofibrillar (+6%), and cytosolic (+7%) quadriceps subfractions was blunted compared to the lean phenotype (+34, +40, and +17%, respectively), indicating a muscle- and subfraction-specific desensitization to the anabolic stimulus of exercise in obese animals.

Dysferlin aggregation in limb-girdle muscular dystrophy type 2B/Miyoshi Myopathy necessitates mutational screen for diagnosis [corrected].

INTRODUCTION: Diagnosis of the limb-girdle muscular dystrophies (LGMDs) has been facilitated by the use of immunofluorescence microscopy, Western blot analysis, and rapid genetic testing. METHODS: We identified 7 patients with LGMD2B or Miyoshi myopathy (MM) phenotypes and performed detailed history, physical examination, and mutation analyses of genomic DNA. RESULTS: Ten disease-causing variants of the dysferlin gene (DYSF) were detected, 4 of which were novel and predicted to be pathogenic (IVS33+9G>T, c.1343T>C, c.4747T>G, and c.5066dupC). Two of these mutations (c.1343T>C and IVS33+9G>T) were associated with a reduction in sarcolemmal dysferlin expression, despite increased total mRNA and protein in mixed muscle homogenates, due to a pathological retention of the mutated polypeptide in the cytoplasm. CONCLUSIONS: Considering that protein-based assays may yield false negative test results and that dysferlin aggregation may be present in other LGMDs, mutational screening is necessary for specific diagnosis in primary dysferlinopathy patients exhibiting this phenotype.