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Background: The efficacy and toxicity of KRASG12C inhibitors were evaluated for advanced solid tumors in several studies; however, the results were not fully consistent. Methods: Clinical trials evaluating KRASG12C inhibitors for advanced solid tumors were searched from PubMed, Embase, and Cochrane Library online databases up to 31st December 2023. The characteristics of the studies and the results of objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) rate, overall survival (OS) rate, and treatment-related adverse events (trAEs) were extracted. Results: Ten studies with 925 heavily pretreated advanced patients harboring KRASG12C mutation were included. For total population, the pooled analysis of ORR was 28.6% (95%CI, 21.2-36.6%), DCR was 85.5% (95%CI, 82.2-88.6%), PFS rate at 6 months (PFS6) was 49.6% (95%CI, 41.4-57.9%), PFS rate at 12 months (PFS12) was 26.7% (95%CI, 19.8-34.1%), OS rates at 6 months (OS6) was 76.2% (95%CI, 68.8-82.9%), OS rates at 12 months (OS12) was 47.8% (95%CI, 38.6-57.0%). The pooled analysis of any grade trAEs was 79.3% (95%CI, 66.2-90.0%) and grade three or more trAEs was 24.4% (95%CI, 16.7-32.9%). The median time to response and DoR results from individual data were 1.39 months (95%CI, 1.37–1.41 months) and 10.54 months (95%CI, 7.72–13.36 months). Sotorasib had significantly lower pooled incidences of any trAEs (OR, 0.07, 95%CI, 0.03–0.14) and grade three or more trAES (OR, 0.34, 95%CI, 0.24–0.49) compared with adagrasib. Conclusions: KRASG12C inhibitors have good ORR, DCR, PFS rate, OS rate, tolerable trAEs, and early response with long duration in advanced solid tumors; however, most of the pooled results were heterogeneous. Sotorasib has shown better safety results. [ABSTRACT FROM AUTHOR]

Introduction: Patient safety and critical care quality remain a challenging issue in the ICU. However, the effects of the national quality improvement (QI) program remain unknown in China.Methods: A national ICU QI program was implemented in a controlled cohort of 586 hospitals from 2016 to 2018. The effects of the QI program on critical care quality were comprehensively investigated.Main Results: A total of 81,461,554 patients were enrolled in 586 hospitals, and 1,587,724 patients were admitted to the ICU over 3 years. In 2018, there was a significantly higher number of ICU beds (2016 vs. 2018: 10668 vs. 13,661, P = 0.0132) but a lower doctor-to-bed ratio (2016 vs. 2018: 0.64 (0.50, 0.83) vs. 0.60 (0.45, 0.75), P = 0.0016) and nurse-to-bed ratio (2016 vs. 2018: 2.00 (1.64, 2.50) vs. 2.00 (1.50, 2.40), P = 0.031) than in 2016. Continuous and significant improvements in the ventilator-associated pneumonia (VAP) incidence rate, microbiology detection rate before antibiotic use and deep vein thrombosis (DVT) prophylaxis rate were associated with the implementation of the QI program (VAP incidence rate (per 1000 ventilator-days), 2016 vs. 2017 vs. 2018: 11.06 (4.23, 22.70) vs. 10.20 (4.25, 23.94) vs. 8.05 (3.13, 17.37), P = 0.0002; microbiology detection rate before antibiotic use (%), 2016 vs. 2017 vs. 2018: 83.91 (49.75, 97.87) vs. 84.14 (60.46, 97.24) vs. 90.00 (69.62, 100), P < 0.0001; DVT prophylaxis rate, 2016 vs. 2017 vs. 2018: 74.19 (33.47, 96.16) vs. 71.70 (38.05, 96.28) vs. 83.27 (47.36, 97.77), P = 0.0093). Moreover, the 6-h SSC bundle compliance rates in 2018 were significantly higher than those in 2016 (6-h SSC bundle compliance rate, 2016 vs. 2018: 64.93 (33.55, 93.06) vs. 76.19 (46.88, 96.67)). A significant change trend was not found in the ICU mortality rate from 2016 to 2018 (ICU mortality rate (%), 2016 vs. 2017 vs. 2018: 8.49 (4.42, 14.82) vs. 8.95 (4.89, 15.70) vs. 9.05 (5.12, 15.80), P = 0.1075).Conclusions: The relationship between medical human resources and ICU overexpansion was mismatched during the past 3 years. The implementation of a national QI program improved ICU performance but did not reduce ICU mortality. [ABSTRACT FROM AUTHOR]

Background: Thalidomide has been reported to cause numerous thromboembolic events. Deep vein thrombosis and pulmonary embolism are more common. It can also cause bradycardia and even total atrioventricular block. Rarely, it causes coronary artery spasm and even myocardial infarction. But almost simultaneous onset of myocardial infarction, third degree atrioventricular block and pulmonary embolism in one patient has not been reported so far.Case Presentation: A 53-year old man presented because of chest pain, nausea and then syncope for several minutes. Previous medical history included neurodermitis for which thalidomide was given and hypercholesterolemia with simvastatin taking. The patient didn't exhibit any other established risk factors for coronary artery disease. Electrocardiography showed sinus rhythm with third degree atrioventricular block and complete right bundle branch block, and precordial leads ST segment elevation. The diagnosis of acute coronary syndrome was suspected, but further coronary angiography demonstrated no flow-limiting lesions in coronary arteries, and temporary pacemaker was implanted. After admission, low SpO2 and elevated D-dimer level was mentioned. Further computed tomography pulmonary angiography revealed pulmonary embolism. Thalidomide was thought to be the cause of hypercoagulability and coronary spasm, so it was ceased immediately. Therapeutic low molecule weight heparin was initiated and then switched to warfarin with appropriate INR, and nifedipine was described for coronary spasm. The patient's symptoms completely relived and SpO2 recovered, and atrioventricular block had disappeared during hospitalization with pacemaker removed.Conclusion: This is the very first case in which myocardial infarction, third degree atrioventricular block and pulmonary embolism almost simultaneously developed. We should be ware that anti-thrombotic prophylaxis, which needs further investigation for optimal drug and dosage, may be beneficial in thalidomide therapy. And it is also important to monitor patients taking thalidomide for signs and symptoms of bradycardia or higher degree atrioventricular block. [ABSTRACT FROM AUTHOR]

Background: This study aimed to identify hotspots in research on clinical competence measurements from 2012 to 2016., Methods: The authors retrieved literature published between 2012 and 2016 from PubMed using selected medical subject headings (MeSH) terms. They used BibExcel software to generate high-frequency MeSH terms and identified hotspots by co-word analysis and cluster analysis., Results: The authors searched 588 related articles and identified 31 high-frequency MeSH terms. In addition, they obtained 6 groups of high-frequency MeSH terms that reflected the domain hotspots., Conclusions: This study identified 6 hotspots of domain research, including studies on influencing factors and perception evaluation, improving and developing measurement tools, feedback measurement, measurement approaches based on computer simulation, the measurement of specific students in different learning phases, and the measurement of students' communication ability. All of these research topics could provide useful information for educators and researchers to continually conduct in-depth studies.

Background: Thalidomide has been reported to cause numerous thromboembolic events. Deep vein thrombosis and pulmonary embolism are more common. It can also cause bradycardia and even total atrioventricular block. Rarely, it causes coronary artery spasm and even myocardial infarction. But almost simultaneous onset of myocardial infarction, third degree atrioventricular block and pulmonary embolism in one patient has not been reported so far., Case Presentation: A 53-year old man presented because of chest pain, nausea and then syncope for several minutes. Previous medical history included neurodermitis for which thalidomide was given and hypercholesterolemia with simvastatin taking. The patient didn't exhibit any other established risk factors for coronary artery disease. Electrocardiography showed sinus rhythm with third degree atrioventricular block and complete right bundle branch block, and precordial leads ST segment elevation. The diagnosis of acute coronary syndrome was suspected, but further coronary angiography demonstrated no flow-limiting lesions in coronary arteries, and temporary pacemaker was implanted. After admission, low SpO2 and elevated D-dimer level was mentioned. Further computed tomography pulmonary angiography revealed pulmonary embolism. Thalidomide was thought to be the cause of hypercoagulability and coronary spasm, so it was ceased immediately. Therapeutic low molecule weight heparin was initiated and then switched to warfarin with appropriate INR, and nifedipine was described for coronary spasm. The patient's symptoms completely relived and SpO2 recovered, and atrioventricular block had disappeared during hospitalization with pacemaker removed., Conclusion: This is the very first case in which myocardial infarction, third degree atrioventricular block and pulmonary embolism almost simultaneously developed. We should be ware that anti-thrombotic prophylaxis, which needs further investigation for optimal drug and dosage, may be beneficial in thalidomide therapy. And it is also important to monitor patients taking thalidomide for signs and symptoms of bradycardia or higher degree atrioventricular block.

Background: The appropriateness of the routine performance of an oral glucose tolerance test (OGTT) to screen for diabetes mellitus (DM) during acute coronary syndrome hospitalization is still under debate., Methods: A systematic search of databases (MEDLINE [1985 to March 2012], EMBASE [1985 to March 2012]) was conducted. All prospective cohort studies assessing the accuracy or reproducibility of an OGTT in ACS or non-ACS individuals were included. A bivariate model was used to calculate the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Heterogeneity was explored using subgroup analysis and meta-regression., Results: Fifteen studies with 8,027 participants were included (10 ACS and 5 non-ACS studies). The pooled results on SEN, SPE, PLR, NLR, and DOR were 0.70 (95% CI, 0.60-0.78), 0.91 (95% CI, 0.86-0.94), 7.6 (95% CI, 4.9-11.7), 0.33 (95% CI, 0.25-0.45), and 23 (95% CI, 12-41), respectively. The OGTT has a slightly lower SPE in diagnosing DM in ACS than in non-ACS patients (0.86 [95% CI 0.81-0.92] versus 0.95 [95% CI 0.93-0.98], p<0.01), while the SEN values are comparable (0.71 [95% CI 0.60-0.82] versus 0.67 [95% CI 0.54-0.81], p=0.43). After adjusting the interval between repeated tests and age, the meta-regression did not show a difference in DOR between ACS and non-ACS studies., Conclusions: Despite the discrepancy in the interval between the two OGTTs, performing an OGTT in patients with ACS provides accuracy that is similar to that in in non-ACS patients. It is reasonable to screen patients hospitalized for ACS for previously undiagnosed DM using an OGTT.