Utility of RAND/UCLA appropriateness method in validating multiple-choice questions on ECG.

OBJECTIVES: This study aimed to investigate the utility of the RAND/UCLA appropriateness method (RAM) in validating expert consensus-based multiple-choice questions (MCQs) on electrocardiogram (ECG). METHODS: According to the RAM user's manual, nine panelists comprising various experts who routinely handle ECGs were asked to reach a consensus in three phases: a preparatory phase (round 0), an online test phase (round 1), and a face-to-face expert panel meeting (round 2). In round 0, the objectives and future timeline of the study were elucidated to the nine expert panelists with a summary of relevant literature. In round 1, 100 ECG questions prepared by two skilled cardiologists were answered, and the success rate was calculated by dividing the number of correct answers by 9. Furthermore, the questions were stratified into "Appropriate," "Discussion," or "Inappropriate" according to the median score and interquartile range (IQR) of appropriateness rating by nine panelists. In round 2, the validity of the 100 ECG questions was discussed in an expert panel meeting according to the results of round 1 and finally reassessed as "Appropriate," "Candidate," "Revision," and "Defer." RESULTS: In round 1 results, the average success rate of the nine experts was 0.89. Using the median score and IQR, 54 questions were classified as " Discussion." In the expert panel meeting in round 2, 23% of the original 100 questions was ultimately deemed inappropriate, although they had been prepared by two skilled cardiologists. Most of the 46 questions categorized as "Appropriate" using the median score and IQR in round 1 were considered "Appropriate" even after round 2 (44/46, 95.7%). CONCLUSIONS: The use of the median score and IQR allowed for a more objective determination of question validity. The RAM may help select appropriate questions, contributing to the preparation of higher-quality tests.

Circulating Syndecan-1 Levels Are Associated with Chronological Coagulofibrinolytic Responses and the Development of Disseminated Intravascular Coagulation (DIC) after Trauma: A Retrospective Observational Study.

BACKGROUND: The purpose of this study was to evaluate the association between endotheliopathy represented by high levels of circulating syndecan-1 (SDC-1) and coagulofibrinolytic responses due to trauma, which can lead to disseminated intravascular coagulation (DIC). METHODS: We retrospectively evaluated 48 eligible trauma patients immediately admitted to our hospital and assessed SDC-1 and coagulofibrinolytic parameters for 7 days after admission. We compared the longitudinal changes of coagulofibrinolytic parameters and SDC-1 levels between two groups (high and low SDC-1) according to median SDC-1 value on admission. RESULTS: The median circulating SDC-1 level was 99.6 (61.1-214.3) ng/mL on admission, and levels remained high until 7 days after admission. Coagulofibrinolytic responses assessed by biomarkers immediately after trauma were correlated with SDC-1 elevation (thrombin-antithrombin complex, TAT: r = 0.352, p = 0.001; antithrombin, AT: r = -0.301, p < 0.001; plasmin-α2-plasmin inhibitor complex, PIC: r = 0.503, p = 0.035; tissue plasminogen activator, tPA: r = 0.630, p < 0.001). Sustained SDC-1 elevation was associated with intense and prolonged coagulation activation, impairment of anticoagulation, and fibrinolytic activation followed by inhibition of fibrinolysis, which are the primary responses associated with development of DIC in the acute phase of trauma. Elevation of circulating SDC-1 level was also associated with consumption coagulopathy and the need for transfusion, which revealed a significant association between high SDC-1 levels and the development of DIC after trauma (area under the curve, AUC = 0.845, cut-off value = 130.38 ng/mL, p = 0.001). CONCLUSIONS: High circulating levels of syndecan-1 were associated with intense and prolonged coagulation activation, impairment of anticoagulation, fibrinolytic activation, and consumption coagulopathy after trauma. Endotheliopathy represented by SDC-1 elevation was associated with trauma induced coagulopathy, which can lead to the development of DIC.

Cricotracheostomy for patients with severe COVID-19: A case control study.

Background: Tracheostomy is an important procedure for the treatment of severe coronavirus disease-2019 (COVID-19). Older age and obesity have been reported to be associated with the risk of severe COVID-19 and prolonged intubation, and anticoagulants are often administered in patients with severe COVID-19; these factors are also related to a higher risk of tracheostomy. Cricotracheostomy, a modified procedure for opening the airway through intentional partial cricoid cartilage resection, was recently reported to be useful in cases with low-lying larynx, obesity, stiff neck, and bleeding tendency. Here, we investigated the usefulness and safety of cricotracheostomy for severe COVID-19 patients. Materials and methods: Fifteen patients with severe COVID-19 who underwent cricotracheostomy between January 2021 and April 2022 with a follow-up period of ≥ 14 days were included in this study. Forty patients with respiratory failure not related to COVID-19 who underwent traditional tracheostomy between January 2015 and April 2022 comprised the control group. Data were collected from medical records and comprised age, sex, body mass index, interval from intubation to tracheostomy, use of anticoagulants, complications of tracheostomy, and decannulation. Results: Age, sex, and days from intubation to tracheostomy were not significantly different between the COVID-19/cricotracheostomy and control/traditional tracheostomy groups. Body mass index was significantly higher in the COVID-19 group than that in the control group (P = 0.02). The rate of use of anticoagulants was significantly higher in the COVID-19 group compared with the control group (P < 0.01). Peri-operative bleeding, subcutaneous emphysema, and stomal infection rates were not different between the groups, while stomal granulation was significantly less in the COVID-19 group (P = 0.04). Conclusions: These results suggest that cricotracheostomy is a safe procedure in patients with severe COVID-19.

Dynamic coagulofibrinolytic responses under long-term VV-ECMO management without anticoagulation in a COVID-19-ARDS patient: A case report.

RATIONALE: Venovenous extracorporeal membrane oxygenation (ECMO) is recommended for the treatment of critically ill patients with acute respiratory distress syndrome due to coronavirus disease 2019 (COVID-19). However, ECMO management can cause both bleeding and thrombotic complications. There are insufficient coagulofibrinolytic data for appropriate ECMO management in patients with COVID-19. PATIENT CONCERNS: A 48-year-old man with severe COVID-19-acute respiratory distress syndrome underwent long-term venovenous ECMO management for 48 days. Refractory oronasal bleeding developed on day 13, so the administration of unfractionated heparin was ceased for 29 days. DIAGNOSIS: The patient showed dynamic coagulofibrinolytic responses associated with ECMO management, as shown by fibrin/fibrinogen degradation products, soluble fibrin, thrombin-antithrombin complex, and plasmin-α2-plasmin inhibitor complex elevations, suggesting the development of ECMO-induced coagulopathy. INTERVENTIONS: We assessed coagulofibrinolytic markers to decide the appropriate timing for controlling excessive activation of coagulation by exchanging ECMO circuits. Moreover, viscoelastic hemostatic assays were used for adequate transfusion of blood products. OUTCOMES: Safe long-term ECMO management was completed, which was withdrawn on day 48. The patient was weaned off mechanical ventilation on day 57 and was transferred to another hospital for rehabilitation. LESSONS: Monitoring the coagulofibrinolytic status using markers and viscoelastic hemostatic assays may be effective for safe long-term ECMO management even without anticoagulant therapy.

Laryngeal complications after endotracheal intubation and prone positioning in patients with coronavirus disease 2019.

Objectives: Laryngeal complications have been reported after endotracheal intubation and prone positioning in patients with critical coronavirus disease 2019 (COVID-19), but their association is unclear. In this study, we investigated the rate of laryngeal complications in patients with COVID-19 compared to an alternative condition (control group). Methods: We retrospectively analyzed the data of 40 patients who underwent endotracheal intubation for either COVID-19 or an alternative condition (control group). Data on age, sex, body mass index (BMI), cardiovascular disease (CVD) risk factors, use of prone therapy, duration of endotracheal intubation, and duration from extubation/tracheostomy to laryngeal evaluation were collected from medical records. Results: There were no significant differences in BMI, frequency of CVD risk factors, duration of endotracheal intubation, or duration from extubation/tracheostomy to laryngeal evaluation between the two groups. In the COVID-19 group, all patients adopted the prone position. In comparison, only one patient in the control group adopted the prone position. Significant differences were observed between the two groups regarding the incidence of vocal fold immobility and laryngeal granuloma. Conclusion: Laryngeal complications were more common in the COVID-19 group than in the control group. Prone positioning may be a risk factor for these complications. Level of Evidence: 4.

ADAMTS13 activity decreases in the early phase of trauma associated with coagulopathy and systemic inflammation: a prospective observational study.

BACKGROUND: We conducted a prospective observational study for investigating the changes in the 13th member of a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS13) and its association with the coagulofibrinolytic response in adult trauma patients. METHODS: In 39 trauma patients hospitalized for longer than 7 days, time-course changes in biomarkers of coagulofibrinolysis and systemic inflammation along with ADAMTS13 activity were examined. The patients were stratified into three groups based on ADAMTS13 activities on admission (day 0): normal group (≥70%), mildly decreased group (≥50 and < 70%) and moderately decreased group (< 50%). RESULTS: Among 39 patients with a median Injury Severity Score (ISS) of 20, 11 patients developed disseminated intravascular coagulation (DIC) and 16 patients required transfusion. Six of 39 patients (15.4%) showed moderate decreased ADAMTS13 activity to < 50%, and 20 patients (51.3%) showed mild drops (≥50 and < 70%). These changes in ADAMTS13 activity on day 0 were significantly correlated with changes in IL-6 and other coagulofibrinolytic markers such as platelet counts, prothrombin time and fibrin/fibrinogen degradation product (FDP). Antithrombin activity (AT) and serum albumin (Alb) level showed significantly positive linear correlations with ADAMTS13 activity (AT: r = 0.513, p < 0.001; Alb: r = 0.647, p < 0.001). Simple logistic regression analyses showed that ADAMTS13 activity, if less than 50%, was significantly correlated with the development of DIC (OR 7.499, 95%CI 1.121-49.242, p = 0.038) and the need for transfusion of fresh frozen plasma (OR 9.000, 95%CI 1.327-61.025, p = 0.028). CONCLUSIONS: ADAMTS13 activity decreased even in the early phase of trauma, which was complicated by coagulopathy and systemic inflammation. Furthermore, the decrease in ADAMTS13 activity was correlated with DIC and plasma transfusion.

Anticoagulation Therapy Using rh-Thrombomodulin and/or Antithrombin III Agent is Associated With Reduction in in-Hospital Mortality in Septic Disseminated Intravascular Coagulation: A Nationwide Registry Study.

We analyzed the Nationwide Registry database on sepsis to examine the effects of an anticoagulation therapy, especially with rh-thrombomodulin (rh-TM) and/or antithrombin (AT) III agent, in septic disseminated intravascular coagulation (DIC) patients. In 3,193 patients enrolled after the exclusion, we investigated the association with in-hospital mortality using Cox proportional hazards models. DIC was diagnosed using the Japanese Association of Acute Medicine (JAAM) and the International Society of Thrombosis and Hemostasis (ISTH) criteria. To analyze the separate treatment effects of rh-TM and/or AT III, we excluded the data of 345 patients treated with all available anticoagulation treatments (rh-TM and/or AT III plus "other anticoagulants": protease inhibitors and heparin/heparinoids). The DIC criterion populations were as follows: JAAM DICs, n = 1,891 and ISTH DICs (overt DIC), n = 1,002. Septic DIC patients were divided into 3 groups: Group 1, no anticoagulation therapy for DIC; Group 2, received rh-TM and/or AT III; and Group 3, received only "other anticoagulants." In JAAM DIC patients, Group 2 did not show an independent association with a reduced risk of in-hospital mortality (hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.73-1.01]) as compared with Group 1. However, in ISTH DIC patients, Group 2 showed an inverse association with the risk of in-hospital mortality (HR 0.74; 95% CI: 0.60-0.92) as compared with Group 1, but the same was not true for Group 3 (HR 0.73; 95% CI: 0.47-1.14). The present results support previous findings of the beneficial effects of anticoagulation therapies in septic DIC, also expands the importance of using rh-TM and/or AT agent for septic overt DIC.

Successful treatment for disseminated intravascular coagulation (DIC) corresponding to phenotype changes in a heat stroke patient.

BACKGROUND: Heat stroke induces coagulofibrinolytic activation, which leads to life-threatening disseminated intravascular coagulation (DIC). However, treatment strategies for DIC in heat stroke have not yet been established, and also, the time course changes in coagulofibrinolytic markers have not been thoroughly evaluated. We report a severe heat stroke case with DIC who was eventually saved by anti-DIC treatments in accordance with changes in coagulofibrinolytic markers. CASE PRESENTATION: A 45-year-old man was found unconscious outside, and his body temperature was elevated to 41.9 °C. For heat stroke, we performed an immediate tracheal intubation under the general anesthesia along with cooling by iced gastric lavage, cold fluid administration, and an intravascular cooling using Thermogard™. About 4 h after admission, his core temperature fell to 37 °C. We assessed coagulofibrinolytic biomarkers and treated in accordance with changes in these parameters. This case exhibited a biphasic change varying from an enhanced to a suppressed fibrinolytic type of DIC depending on the relative balance between fibrinolytic activation and the level of plasminogen activator inhibitor-1 (PAI-1). In the early phase with consumption coagulopathy and enhanced fibrinolysis, we transfused a large amount of fresh frozen plasma (FFP) and platelets with tranexamic acid, an antifibrinolytic agent, possibly providing relief for the bleeding tendency. Anticoagulant therapy using recombinant human thrombomodulin-α (rh-TM-α) and antithrombin III (ATIII) concentrate was especially effective for DIC with a suppressed fibrinolytic phenotype in the later phase, after which organ failure that included severe hepatic failure was remarkably improved. CONCLUSION: The present case may indicate the clinical significance of monitoring coagulifibrinolytic changes and the potential benefits of anticoagulants for heat stroke-induced DIC.

Decreased antithrombin activity in the early phase of trauma is strongly associated with extravascular leakage, but not with antithrombin consumption: a prospective observational study.

BACKGROUND: We conducted a prospective observational study for investigating coagulofibrinolytic changes and mechanisms of antithrombin (AT) alternations in trauma. METHODS: Trauma patients hospitalized for more than seven days were analyzed for coagulofibrinolytic biomarkers. The patients were stratified into two groups according to AT activity level on admission (day 0), comprising normal AT and low AT patients. RESULTS: Thirty-nine patients (median Injury Severity Score 20) exhibited initial coagulatory activation and triphasic fibrinolytic changes. AT activity did not show a negative linear correlation with levels of thrombin-antithrombin complex (TAT), a marker of coagulation activity and AT consumption, but was strongly correlated with levels of albumin (Alb), an index of vascular permeability, on day 0 (r = 0.702, p <  0.001). Furthermore, Alb was one of the independent predictors for AT on day 0. IL-6 on day 0 and thrombomodulin (TM) levels during the study period, reflecting systemic inflammation and endothelial cell injury, respectively, were significantly higher in the lower AT group (n = 10) than in the normal group (n = 29) (IL-6, p = 0.004; TM, p = 0.017). On days 2 and 4, TAT levels in the lower AT group were significantly higher than in the normal group. CONCLUSIONS: Trauma caused clear triphasic coagulofibrinolytic changes. Decreased AT in the later phase might lead to a prolonged hypercoagulation. AT reduction in the initial phase of trauma is strongly associated with extravascular leakage as suggested by the association of Alb depletion with IL-6 and TM elevation, but not with AT consumption.

Sudden cerebral depression detected by bispectral index monitoring in cryptococcal meningitis with elevated near-fatal cerebrospinal fluid pressure.

Case: An increase in cerebrospinal fluid pressure (CSFP) is usually prominent in cryptococcal meningitis, which has a high mortality rate, so aggressive management to control CSFP is crucial. In this case, a 40-year-old-man survived cryptococcal meningitis treated with continuous spinal drainage under bispectral index (BIS) monitoring. He unexpectedly showed hypertension, went into a coma, and even loss his light reflexes due to CSFP elevation. His BIS values had abruptly dropped before developing these symptoms, but dramatically recovered after lumbar puncture drainage, suggesting that BIS monitoring could reflect cerebral function changes due to CSFP alternations. Outcome: Inducing continuous spinal drainage to control CSFP provided stable control of blood pressure and brain activity, which was continuously monitored by BIS, enabling us to provide prompt treatment. Conclusion: Cerebral depressions due to elevated CSFP may suddenly develop, so continuous spinal drainage is needed for preventing catastrophic events. Bispectral index could be useful for detecting early changes from CSFP elevation in meningitis cases with intracranial hypertension.

Short-term clinical results of arthroscopic osteochondral fixation for elbow osteochondritis dissecans in teenaged baseball players.

BACKGROUND: Reports regarding arthroscopic fixation of the osteochondral fragments for elbow osteochondritis dissecans (OCD) are few. This study assessed the clinical outcomes of arthroscopic fixation of unstable osteochondral fragments by using absorbable pins over a postoperative period of at least 1 year. METHODS: The patients were 13 adolescent baseball players with a mean age of 14 years (range, 12-16 years) who underwent OCD of primary lesions at International Cartilage Repair Society grades III and IV. The patients were evaluated by using validated outcome measures at a mean follow-up period of 24 months (range, 12-50 months). RESULTS: The mean (standard deviation) score in the disability/symptom section of the Disabilities of the Arm, Shoulder, and Hand improved from 12.4 (6.0) before the surgery to 0.5 (1.2) after the surgery, and the sports section improved from 74.5 (25.4) to 1.4 (5.2). The mean (standard deviation) extension improved from -11° (10.8) to -2° (3.9; P < .001). The mean (SD) flexion improved from 129° (11.6) to 137° (5.6; P = .040). All patients were able to resume playing baseball, and 9 (69%) resumed playing at the same position as before their injuries. CONCLUSIONS: The clinical results of arthroscopic osteochondral fragment fixation in the teenaged baseball players with elbow OCD, albeit obtained over only a short period, were favorable. This arthroscopic treatment enables repair of lesions and is considered appropriate for unstable OCD during the adolescent growth spurt.