Myelodysplastic Neoplasms (MDS) with Ring Sideroblasts or SF3B1 Mutations: The Improved Clinical Utility of World Health Organization and International Consensus Classification 2022 Definitions, a Single-Centre Retrospective Chart Review.

Myelodysplastic neoplasms (MDS) with ring sideroblasts (RS) are diagnosed via bone marrow aspiration in the presence of either (i) ≥15% RS or (ii) 5-14% RS and an SF3B1 mutation. In the MEDALIST trial and in an interim analysis of the COMMANDS trial, lower-risk MDS-RS patients had decreased transfusion dependency with luspatercept treatment. A total of 6817 patients with suspected hematologic malignancies underwent molecular testing using a next-generation-sequencing-based genetic assay and 395 MDS patients, seen at our centre from 1 January 2018 to 31 May 2023, were reviewed. Of these, we identified 39 evaluable patients as having lower-risk MDS with SF3B1 mutations: there were 20 (51.3%) males and 19 (48.7%) females, with a median age of 77 years (range of 57 to 92). Nineteen (48.7%) patients had an isolated SF3B1 mutation with a mean variant allele frequency of 35.2% +/- 8.1%, ranging from 7.4% to 46.0%. There were 29 (74.4%) patients with ≥15% RS, 6 (15.4%) with 5 to 14% RS, one (2.6%) with 1% RS, and 3 (7.7%) with no RS. Our study suggests that a quarter of patients would be missed based on the morphologic criterion of only using RS greater than 15% and supports the revised 2022 definitions of the World Health Organization (WHO) and International Consensus Classification (ICC), which shift toward molecularly defined subtypes of MDS and appropriate testing.

Catastrophic antiphospholipid syndrome refractory to high-dose intravenous immunoglobulin responsive to therapeutic plasma exchange.

Catastrophic antiphospholipid syndrome (CAPS) involves sudden multiorgan dysfunction from thrombosis due to antibodies that cause platelet activation and endothelial dysfunction. Treatment variably combines anticoagulation, corticosteroid use, therapeutic plasma exchange (TPE), and high-dose intravenous immunoglobulin (IVIG). A 42-year-old male with antiphospholipid syndrome (APS) presented with severe thrombocytopenia, encephalopathy, cardiac ischemia, and acral purpuric cutaneous lesions. CAPS was identified and he received heparin infusion, methylprednisolone, and IVIG. On day 7 he developed new purpuric lesions on his right foot despite detectable arterial pulses representing new microthrombosis refractory to IVIG. He was treated with TPE which resolved the right foot ischemia and eventually his CAPS. To our knowledge, this is the first patient with CAPS reported that failed initial treatment with IVIG and subsequently had excellent response to TPE. Our observations also support recent literature indicating that onset of thrombocytopenia in APS is a warning of progression to CAPS requiring treatment escalation.

Blood loss from laboratory testing, anemia, and red blood cell transfusion in the intensive care unit: a retrospective study.

BACKGROUND: Anemia is common in critically ill patients and associated with adverse outcomes. Phlebotomy associated with laboratory testing is a potentially modifiable contributor. This study aims to 1) characterize the blood volume taken for laboratory testing, and 2) explore the effect of blood loss on red blood cell (RBC) transfusion and anemia in adult intensive care unit (ICU) patients. METHODS: Using a transfusion research database, we retrospectively reviewed consecutively admitted patients to four medical-surgical ICUs in Hamilton, Ontario, Canada. The primary outcome was estimated blood loss for laboratory testing during ICU admission. Secondary outcomes were hemoglobin (Hb) of 90 g/L or less and RBC transfusion. RESULTS: Among the 7273 patients included, the median blood volume per patient taken for laboratory testing during their ICU stay was 213 mL (interquartile range [IQR], 133-382 mL). On ICU admission, median Hb was 97 g/L (IQR, 82-116 g/L). An Hb of 90 g/L or less occurred in 67.0% of patients during their ICU stay. Median Hb on ICU discharge adjusted for RBC transfusion was 84 g/L (IQR, 58-105 g/L). RBC transfusion was administered to 47.5% of patients, who received a median of 3 units (IQR, 2-7 units). Cumulative blood loss due to laboratory testing from Day 2 to Day 7 of ICU admission was independently associated with RBC transfusion (hazard ratio, 2.28 for each 150-mL increment; 95% confidence interval, 2.02-2.59). CONCLUSIONS: Blood loss for laboratory testing is substantial in ICU patients and significantly associated with RBC transfusion. Strategies to reduce blood loss from laboratory testing represents an area for further investigation.

Reporting preclinical anesthesia study (REPEAT): Evaluating the quality of reporting in the preclinical anesthesiology literature.

Poor reporting quality may contribute to irreproducibility of results and failed 'bench-to-bedside' translation. Consequently, guidelines have been developed to improve the complete and transparent reporting of in vivo preclinical studies. To examine the impact of such guidelines on core methodological and analytical reporting items in the preclinical anesthesiology literature, we sampled a cohort of studies. Preclinical in vivo studies published in Anesthesiology, Anesthesia & Analgesia, Anaesthesia, and the British Journal of Anaesthesia (2008-2009, 2014-2016) were identified. Data was extracted independently and in duplicate. Reporting completeness was assessed using the National Institutes of Health Principles and Guidelines for Reporting Preclinical Research. Risk ratios were used for comparative analyses. Of 7615 screened articles, 604 met our inclusion criteria and included experiments reporting on 52 490 animals. The most common topic of investigation was pain and analgesia (30%), rodents were most frequently used (77%), and studies were most commonly conducted in the United States (36%). Use of preclinical reporting guidelines was listed in 10% of applicable articles. A minority of studies fully reported on replicates (0.3%), randomization (10%), blinding (12%), sample-size estimation (3%), and inclusion/exclusion criteria (5%). Statistics were well reported (81%). Comparative analysis demonstrated few differences in reporting rigor between journals, including those that endorsed reporting guidelines. Principal items of study design were infrequently reported, with few differences between journals. Methods to improve implementation and adherence to community-based reporting guidelines may be necessary to increase transparent and consistent reporting in the preclinical anesthesiology literature.

Ischemic and bleeding outcomes after coronary artery bypass grafting among patients initially treated with a P2Y12 receptor antagonist for acute coronary syndromes: Insights on timing of discontinuation of ticagrelor and clopidogrel prior to surgery.

BACKGROUND: Clinical outcomes in acute coronary syndrome patients treated with P2Y12 inhibitors who require urgent coronary artery bypass grafting (CABG) have not been well studied. METHODS: We examined clinical outcomes in acute coronary syndrome patients in relation to the timing of CABG following P2Y12 inhibitor discontinuation (<72 h, 72 h to five days, >5 days). The primary ischemic outcome was a composite of death, reinfarction, need for revascularization, or stroke. The primary safety outcome was bleeding of at least moderate severity as defined by a Universal Definition of Perioperative Bleeding class ≥2. RESULTS: Among 508 patients (95 ticagrelor, 413 clopidogrel), the timing of CABG following P2Y12 inhibitor discontinuation was <72 h in 32.1%, 72 h to five days in 23.2% and >5 days in 44.7%. Compared with CABG within 72 h, CABG 72 h to five days (adjusted odds ratio (OR) 0.35; 95% confidence interval (CI) 0.14-0.85; p=0.02) but not >5 days (adjusted OR 0.62; 95% CI 0.33-1.16; p=0.14) after P2Y12 inhibitor discontinuation was associated with lower odds of the primary ischemic outcome. Compared with CABG within 72 h, CABG 72 h to five days (adjusted OR 0.38; 95% CI 0.22-0.66; p=0.001) and >5 days (adjusted OR 0.33; 95% CI 0.20-0.53; p<0.001) after P2Y12 inhibitor discontinuation were associated with lower rates of Universal Definition of Perioperative Bleeding class ≥2 bleeding. CONCLUSIONS: CABG within 72 h after P2Y12 inhibitor discontinuation is associated with excess ischemia and bleeding. The rates of ischemic and bleeding events were comparable in patients undergoing CABG 72 h to five days compared with >5 days after P2Y12 inhibitor discontinuation.

Optimal mean arterial pressure in comatose survivors of out-of-hospital cardiac arrest: An analysis of area below blood pressure thresholds.

AIM OF THE STUDY: To determine the optimal mean arterial pressure (MAP) during the early-to-intermediate phase care of comatose survivors of out-of-hospital cardiac arrest (OHCA). METHODS: We identified consecutive comatose survivors of OHCA with an initial shockable rhythm. Using blood pressure-over-time plots, we calculated the area below pre-specified MAP thresholds (ABT; mmHg*hours) during the first 96 h of admission. We used incremental MAP thresholds ranging between 65 and 85 mmHg. Logistic regression analyses were used to examine the association between ABT and clinical outcomes for each MAP threshold and to adjust for age, duration of cardiac arrest, and bystander CPR. The primary outcome was severe neurological dysfunction as defined by a cerebral performance category (CPC) ≥3. RESULTS: We identified 122 consecutive OHCA patients meeting inclusion criteria. The rate of the primary outcome was 33%. There was a significant association between ABT and the rate of the primary outcome when MAP thresholds of 60 (p = 0.01), 65 (p < 0.01), 70 (p < 0.01), 75 (p < 0.01), and 80 mmHg (p < 0.01) were used. This association was lost once a MAP threshold of 85 mmHg was reached (p = 0.63). In the adjusted analysis, the association between ABT and the primary outcome was no longer present when the MAP threshold reached 75 mmHg. CONCLUSIONS: In comatose survivors of OHCA with an initial shockable rhythm, higher ABT is associated with increased rates of severe neurological dysfunction when MAP thresholds <75 mmHg are used. The current findings support the hypothesis that higher MAP targets (≥75 mmHg) may be indicated in this patient population.

Hyperglycaemia in comatose survivors of out-of-hospital cardiac arrest.

BACKGROUND: The optimal blood glucose target during the early hospitalisation of comatose survivors of out-of-hospital cardiac arrest (OHCA) has not been established. METHODS: In a retrospective cohort study, we examined clinical outcomes in relation to mean blood glucose during the first 96 hours of hospital admission in comatose survivors of OHCA with an initial shockable rhythm. Mean blood glucose was assessed as a continuous (primary analysis) and categorical variable: <6 mmol/L, 6 to <8 mmol/L and ⩾8 mmol/L. Co-primary outcomes were the rates of death during the index hospitalisation and severe neurological dysfunction at discharge. We used multivariable logistic regression analyses to adjust for baseline differences in patient and index event characteristics. RESULTS: Among 122 eligible patients, death and severe neurological dysfunction occurred in 29 (24%) and 40 (33%) patients, respectively. Higher mean blood glucose levels during the first 96 hours of admission were associated with increased odds of death (odds ratio (OR): 1.50; 95% confidence interval (CI): 1.17-1.92; p = 0.001) and severe neurological dysfunction (OR: 1.42; 95% CI: 1.11-1.80; p = 0.004). The associations between mean blood glucose and the odds of death (OR: 1.35; 95% CI: 1.04-1.76; p = 0.02) and severe neurological dysfunction (OR: 1.28; 95% CI: 1.00-1.64; p = 0.05) persisted after adjusting for age, time from cardiac arrest to return of spontaneous circulation (ROSC) and vasoactive agent use. There was no interaction between age, time from cardiac arrest to ROSC or a history of diabetes mellitus and the relationship between mean blood glucose and co-primary outcomes. CONCLUSIONS: In comatose survivors of OHCA with initial shockable rhythms, higher mean blood glucose levels during the first 96 hours of admission are associated with increased rates of death and severe neurological dysfunction.

Impact of mean arterial pressure on clinical outcomes in comatose survivors of out-of-hospital cardiac arrest: Insights from the University of Ottawa Heart Institute Regional Cardiac Arrest Registry (CAPITAL-CARe).

AIM OF THE STUDY: We sought to assess the relationship between mean arterial pressure (MAP) and clinical outcomes in comatose survivors of out-of-hospital cardiac arrest (OHCA). METHODS: We identified consecutive comatose survivors of OHCA with an initial shockable rhythm treated with targeted temperature management. We examined clinical outcomes in relation to mean MAP (measured hourly) during the first 96h of hospitalization. Co-primary outcomes were the rates of death and severe neurological dysfunction at discharge. RESULTS: In 122 patients meeting inclusion criteria, death occurred in 29 (24%) and severe neurological dysfunction in 39 (32%). Higher mean MAPs were associated with lower odds of death (OR 0.55 per 5mmHg increase; 95%CI 0.38-0.79; p=0.002) and severe neurological dysfunction (OR 0.66 per 5mmHg increase; 95%CI 0.48-0.90; p=0.01). After adjustment for differences in patient, index event, and treatment characteristics, higher mean MAPs remained associated with lower odds of death (OR 0.60 per 5mmHg increase; 95%CI 0.40-0.89; p=0.01) but not severe neurological dysfunction (OR 0.73 per 5mmHg increase; 95%CI 0.51-1.03; p=0.07). The relationship between mean MAP and the odds of death (p-interaction=0.03) and severe neurological dysfunction (p-interaction=0.03) was attenuated by increased patient age. CONCLUSION: In comatose survivors of OHCA treated with target temperature management, a higher mean MAP during the first 96h of admission is associated with increased survival. The association between mean MAP and clinical outcomes appears to be attenuated by increased age.

Acquired Factor XIII Inhibitor in Hospitalized and Perioperative Patients: A Systematic Review of Case Reports and Case Series.

Factor XIII (FXIII) cross-links fibrin monomers to support clot stabilization and wound healing. Acquired FXIII deficiency is caused by autoantibodies that inhibit FXIII and can result in bleeding despite normal routine coagulation test results. Given the rarity of this disease, large clinical studies are not feasible. We therefore conducted a systematic review of case reports and case series of acquired FXIII inhibitor to evaluate potential management and treatment strategies for acquired FXIII inhibitor in hospitalized and/or perioperative patients. A systematic search of MEDLINE, Embase, and Web of Science identified reports of hospitalized and perioperative patients with acquired FXIII deficiency. No restrictions were placed on language or publication type. Article screening and data extraction were performed independently by 2 abstractors. Completeness of reporting was evaluated according to modified elements from the CAse REport (CARE) guidelines. A total of 1028 citations were reviewed, with 36 case reports and 3 case series meeting eligibility criteria (63 patients total). The mean age was 60 (range, 9-87) years with balanced sex representation. At presentation, 48 patients (76%) had intramuscular or subcutaneous bleeding, and 34 patients (54%) had external or surgical bleeding. All cases were diagnosed by initially detecting a FXIII deficiency and then identifying the inhibitor. Clinical improvement in bleeding was seen in patients receiving FXIII concentrate (13/17 patients), cryoprecipitate (5/8), and plasma (10/18). Inhibitor reduction was seen in patients who received rituximab (6/6 patients), plasma exchange (2/2), intravenous immunoglobulin (4/5), steroid (15/20), and cyclophosphamide (10/15). Concurrent initiation of multiple therapies and obvious lack of control comparisons made direct association to outcomes difficult to establish. Outcomes were reported for 55 patients, with 25 patients (45%) having complete inhibitor eradication and 15 patients (27%) having partial resolution; 9 of these patients (14%) had a relapse. Thirteen patients (20%) died (7 from internal hemorrhage). Completeness of reporting varied for specific CAse REport items. Patient demographics, clinician-assessed outcomes, and laboratory test results were reported in all case reports. Least reported items included informed consent (6%), patient perspective (3%), and a title containing the words case report (9%). Our systematic review provides the most complete overview of published reports of FXIII acquired inhibitor to date. There is a paucity of data available on FXIII acquired inhibitor, and the available data may be limited by variable reporting. Despite multimodal therapy, a significant proportion of patients with FXIII acquired inhibitor have a large burden of morbidity and mortality.