Elevated Myocardial Enzymes Research Articles

IMPACT OF COVID-19 ON DIAGNOSTIC ANALYSIS OF MYOCARDITIS

Introduction: Myocarditis is a disease caused by inflammation of the heart muscle, the myocardium. The myo-cardium is responsible for contracting and relaxing to pump blood in and out of the heart and the rest of the body. When this muscle becomes inflamed, its ability to pump blood becomes less effective. This causes prob-lems such as abnormal heartbeat, chest pain, or breathing disorders. In extreme cases, it can also cause blood clots that lead to heart attack, stroke, and even death. Purpose: To study the aggravating factors of COVID-19 that caused myocarditis and its prevention. Despite the distinctive clinical signs of patients with COVID-19, there are still elements that remain undiscovered, such as the prognostic factors of COVID-19, which include external factors, such as viral load and internal factors, which include the health conditions of the individual, the incidence rate of myocarditis and distinguishing signs. Materials and Methods: This is a retrospective study highlighting the clinical and radiographic signs of the above cases diagnosed with COVID-19. Demographic, epidemiologic, radiologic, and laboratory data collected from medical record reviews of adult patients diagnosed with COVID-19 provided the basis for their follow-up. Measurement of the cycle threshold value (Ct), real-time PCR (RT-PCR), electrocardiogram (ECG), and meas-urement of pulmonary inflammation index (PII) values were among the most frequent examinations performed in these patients. Results: In the study, 75 adult patients diagnosed with COVID-19 admitted to QSUNT were included, of which 15 cases were severe and 60 were in stable condition. The viral load of severe cases was significantly higher than that of stable patients, regardless of PCR values. Typical Ct abnormalities were more likely to exist in the severe group than in the non-severe group, associated with consolidation and thickening of the interlobular sep-tum and increased PII values. Of the 75 patients, 12 patients were noted to have an abnormal ECG and elevated serum myocardial enzyme levels, and five were clinically diagnosed with SARS-COV-2-induced myocarditis. Conclusion: During the patient study, three independent risk factors of COVID-19 were identified, which in-cluded age, PII, and Ct value. The Ct value is closely related to the severity of COVID-19 and may act as a pre-dictor of the clinical severity of early-stage COVID-19. Oxygen pressure, along with laboratory tests, are ele-ments that should not be neglected as they are also closely related to the severity of COVID-19.

Bronchial artery embolization leading to acute myocardial infarction: a case report on bronchial artery-coronary artery fistula

A 22-year-old woman presented with hemoptysis for three days, averaging 150 ml of blood per day. She had no history of childhood chest disease. On admission, a chest scan suggested a potential lung infection, and laboratory results showed no significant abnormalities. Despite continuous infusion of posterior pituitary hormone, her symptoms persisted. We performed bronchial arteriography and embolization using 150–350 μm microsphere particles. During the procedure, the patient developed chest pain. An electrocardiogram (ECG) showed abnormal Q-waves and ST-T elevation, with vital signs indicating hypotension and elevated myocardial enzymes suggesting acute myocardial infarction (AMI). Repeated arteriography revealed a bronchial artery-right coronary artery fistula, likely worsened by a dislodged gelatin sponge blocking coronary microvessels. The embolization was halted, and treatment with low molecular weight heparin and aspirin was initiated. By the fifth postoperative day, the patient’s ECG indicated an abnormal Q wave in the inferior leads, and myocardial enzymes were gradually returning to normal. One week later, coronary angiography revealed no blockage, and the patient was discharged after stabilization. The cardiovascular magnetic resonance (CMR) indicated myocardial necrosis and edema in the inferior wall of the heart. During subsequent follow-up, the patient reported no significant chest pain or recurrence of hemoptysis.

Guanfacine poisoning resulting in transient ST-segment elevation: a case report

BackgroundGuanfacine is an alpha-2 adrenergic agonist that decreases norepinephrine release and sympathetic outflow. With the increased use of guanfacine for attention-deficit hyperactivity disorder (ADHD), reports of guanfacine poisoning have also risen.Case presentationA 15-year-old male (height: 170 cm, weight: 48 kg), who was taking 2 mg/day of guanfacine for ADHD, was brought to our emergency department after ingesting 40 tablets of guanfacine due to poor exam results. He presented with impaired consciousness and sinus bradycardia on an electrocardiogram (ECG), leading to diagnosis of guanfacine poisoning. Gastric lavage (5 L) was performed, and activated charcoal was administered. Although his consciousness gradually recovered, he developed ST-segment elevation on the ECG. Despite the absence of chest pain and elevated myocardial enzymes, coronary artery stenosis was not observed on coronary artery computed tomography. As his blood guanfacine level decreased, his ECG returned to normal.ConclusionsThis case highlights the need for careful monitoring of guanfacine poisoning patients due to the potential for various cardiovascular events.

Podophyllotoxin via SIRT1/PPAR /NF-κB axis induced cardiac injury in rats based on the toxicological evidence chain (TEC) concept

BackgroundThe study of cardiotoxicity of drugs has become an important part of clinical safety evaluation of drugs. It is commonly known that podophyllotoxin (PPT) and its many derivatives and congeners are broad-spectrum pharmacologically active substances. Clinical cardiotoxicity of PPT and its derivatives has been raised, basic research on the mechanism of cardiotoxicity remains insufficient. PurposeIn present study, our group's innovative concept of toxicological evidence chain (TEC) was applied to reveal the cardiac toxicity mechanism of PPT by targeted metabolomics, TMT-based quantitative proteomics and western blot. MethodsThe injury phenotype evidence (IPE) acquired from the toxicity manifestations, such as weight and behavior observation of Sprague-Dawley rat. The damage to rat hearts were assessed through histopathological examination and myocardial enzymes levels, which were defined as Adverse Outcomes Evidence (AOE). The damage to rat hearts was assessed through histopathological examination and myocardial enzyme levels, which were defined as evidence of adverse outcomes.Overall measurements of targeted metabolomics based on energy metabolism and TMT-based quantitative proteomics were obtained after exposure to PPT to acquire the Toxic Event Evidence (TEE). The mechanism of cardiac toxicity was speculated based on the integrated analysis of targeted metabolomics and TMT-based quantitative proteomics, which was verified by western blot. ResultsThe results indicated that exposure to PPT could result in significant elevation of myocardial enzymes and pathological alterations in rat hearts. In addition, we found that PPT caused disorders in cardiac energy metabolism, characterized by a decrease in energy metabolism fuels. TMT-based quantitative proteomics revealed that the PPAR (Peroxisome proliferators-activated receptor) signaling pathway needs further study. It is worth noting that PPT may suppress the expression of SIRT1, subsequently inhibiting AMPK, decreasing the expression of PGC-1α, PPARα and PPARγ. This results in disorders of glucose oxidation, glycolysis and ketone body metabolism. Additionally, the increase in the expression of p-IKK and p-IκBα, leads to the nuclear translocation of NF-κB p65 from the cytosol, thus triggering inflammation. ConclusionThis study comprehensively evaluated cardiac toxicity of PPT and initially revealed the mechanism of cardiotoxicity,suggesting that PPT induced disorders of energy metabolism and inflammation via SIRT1/PPAR/NF-κB axis, potentially contributing to cardiac injury.

Gradually elevated myocardial enzymes.

Gradually elevated myocardial enzymes.

Recurrent myocardial injury in a de novo SON mutation ZTTK syndrome patient: a case report

BackgroundZhu-Tokita-Takenouchi-Kim syndrome (ZTTK syndrome) is a severe multi-systemic developmental disorder, caused by variants in the SON gene. A patient diagnosed with ZTTK syndrome who carried a de novo SON mutation and exhibited recurrent myocardial injury was described in this case.Case presentationA 7-year-old girl was admitted to the Cardiology Department of Beijing Children’s Hospital in November 2019 due to myocardial injury following respiratory infection. She displayed elevated myocardial enzymes and severe T-wave changes on electrocardiogram. Over the past three years, she had experienced myocardial injury on three occasions. Additionally, she exhibited intellectual disability, congenital amblyopia, and dysmorphic facial features. Genetic analysis revealed a de novo heterozygous mutation c.3852_3856delGGTAT in the SON gene, which was confirmed by Sanger sequencing of her parents. She received anti-infection treatment and was administered metoprolol orally. Her condition was stable at the time of discharge. Over a 42-month follow-up period at the outpatient clinic, she complained intermittent fatigue and palpitation.ConclusionsThe identified SON mutation, which plays a crucial role in heart development and mitochondrial function, may be associated with an increased susceptibility to myocardial injury or cardiomyopathy. This case report contributes novel insights into this rare condition and suggests the expansion of the ZTTK syndrome phenotype.

Regulatory mechanism of perinatal nonylphenol exposure on cardiac mitochondrial autophagy and the PINK1/Parkin signaling pathway in male offspring rats

ObjectiveThis study investigated whether perinatal exposure to nonylphenol (NP) induces mitochondrial autophagy (i.e., mitophagy) damage in neonatal rat cardiomyocytes (NRCMs) and whether the PINK1/Parkin signaling pathway is involved in NP-induced primary cardiomyocyte injury. Methods and resultsIn vivo: Perinatal NP exposure increased apoptosis and mitochondrial damage in NRCMs. Mitochondrial swelling and autophagosome-like structures with multiple concentric membranes were observed in the 100 mg/kg NP group, with an increase in the number of autophagosomes. Disorganized fiber arrangement and elevated serum myocardial enzyme levels were observed with increasing NP dosage. Additionally, NP exposure led to increased MDA levels and decreased SOD activity and ATP levels in myocardial tissue. The mRNA expression levels of autophagy-related genes, including Beclin-1, p62, and LC3B, as well as the expression of mitochondrial autophagy–related proteins (PINK1, p-Parkin, Parkin, Beclin-1, p62, LC3-I, LC3-II, and LC3-II/I) and apoptosis-related proteins (Bax and caspase-3), increased, whereas the expression levels of the mitochondrial membrane protein TOMM20 and the anti-apoptotic protein Bcl-2 decreased. In vitro: NP increased ROS levels, LDH release, and decreased ATP levels in NRCMs. CsA treatment significantly inhibited the expression of autophagy-related proteins (Beclin-1, LC3-II/I, and p62) and apoptosis-related proteins (caspase-3 and Bax), increased the expression levels of TOMM20 and Bcl-2 proteins, increased cellular ATP levels, and inhibited LDH release. The inhibition of the PINK1/Parkin signaling pathway suppressed the expression of mitochondrial autophagy–related proteins (PINK1, p-Parkin, Parkin, Beclin-1, LC3-II/I, and p62) and apoptosis-related proteins (caspase-3 and Bax), increased TOMM20 and Bcl-2 protein expression, increased ATP levels, and decreased LDH levels in NRCMs. ConclusionsThis study is novel in reporting that perinatal NP exposure induced myocardial injury in male neonatal rats, thereby inducing mitophagy. The PINK1/Parkin signaling pathway was involved in this injury by regulating mitophagy.

Intraoperative blood pressure and cardiac complications after aneurysmal subarachnoid hemorrhage: a retrospective cohort study.

Previous studies report that intraoperative hypotension worsens outcomes after aneurysmal subarachnoid hemorrhage (aSAH). However, the hypotensive harm threshold for major adverse cardiovascular events (MACE) remains unclear. The authors included aSAH patients who had general anesthesia for aneurysmal clipping/coiling. MACE were defined by a composite of acute myocardial injury, acute myocardial infarction, and other cardiovascular complications identified by electrocardiogram and echocardiography. The authors initially used logistic regression and change-point analysis based on the second derivative to identify mean arterial pressure (MAP) of 75mmHg as the harm threshold. Thereafter, our major exposure was MAP below 75mmHg characterized by area, duration, and time-weighted average. The area below 75mmHg represents the severity and duration of exposure and was defined as the sum of all areas below a specified threshold using the trapezoid rule. Time-weighted average MAP was derived by dividing area below the threshold by the duration of anesthesia. All analyses were adjusted for baseline risk factors including age greater than 70 years, female sex, severity of intracerebral hemorrhage, history of cardiovascular disease, and preoperative elevated myocardial enzymes. Among 1029 patients enrolled, 254 (25%) developed postoperative MACE. Patients who experienced MACE were slightly older (59±11 vs. 54±11 years), were slightly more often women (69 vs. 58%), and had a higher prevalence of cardiovascular history (65 vs. 47%). Adjusted cardiovascular risk increased nearly linearly over the entire range of observed MAP. However, there was a slight inflexion at MAP of 75mmHg. MACE was significantly associated with area [adjusted odds ratios (aOR) 1.004 per 10mmHg.min, 95% CI: 1.001-1.007, P =0.002), duration (aOR 1.031 per 10min, 95% CI: 1.009-1.054, P =0.006), and time-weighted average (aOR 3.516 per 10mmHg, 95% CI: 1.818-6.801, P <0.001) of MAP less than 75mmHg. Lower blood pressures were associated with cardiovascular complications over the entire observed range, but worsened when MAP was less than 75mmHg. Pending trial data to establish causality, it may be prudent to keep MAP above 75mmHg in patients having surgical aSAH repairs to reduce the risk of MACE.

Analysis of clinical and genetic variation in neonatal intrahepatic cholestasis caused by citrin deficiency

Objective: To investigate the clinical phenotype and gene variation conditions in neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), so as to provide a basis for genetic counseling and clinical diagnosis and treatment of the family. Methods: 11 cases of neonatal intrahepatic cholestasis who visited the Children's Hospital Affiliated to Zhengzhou University between February 2019 and March 2021 were selected as the study subjects. High-throughput sequencing technology was used to detect the gene variation condition in 11 neonatal patients and 100 normal control neonates. The suspicious loci and family members were verified by Sanger sequencing and QPCR technology. Results: All 11 children with NICCD had different degrees of jaundice and liver damage symptoms, combined with coagulation dysfunction and anemia (n = 7), cardiac malformation (n = 2), elevated myocardial enzymes (n = 4), hyperlipidemia (n = 1), hyperkalemia (n = 1), persistent diarrhea (n = 3), developmental delay (n = 1). A total of 10 different types of SLC25A13 gene mutations were detected in 11 cases, including three frameshift mutations, two splicing changes, two missense mutations, one intron insertion, one nonsense mutation, and one heterozygous deletion. After reviewing literature and databases, c.1878delG(p.I627Sfs*73) and exon11 deletion were novel mutations that had not been reported at home or abroad. Conclusion: The clinical features of NICCD are non-specific, and genetic testing aids in the early and accurate diagnosis of the disease, providing an important basis for clinical treatment and genetic counseling for family members. In addition, the detection of novel mutation sites has enriched the SLC25A13 gene variation spectrum.

P436 ASSOCIATION BETWEEN REVERSE–TAKO–TSUBO E NEUROLOGICAL DISORDER

Abstract Reverse–Tako–tsubo (r–TTC) is a rare variant of Tako–tsubo syndrome (TTC). TTC is characterized by transient and reversible left ventricular systolic dysfunction, for which an emotional or physical stressful trigger can usually be identified. Clinically, it mimics an acute myocardial infarction, with elevation of myocardial cytonecrosis enzymes and no obstractive coronary artery stenosis. On imaging, r–TTC is characterized by hypokinesia of the mid–basal regions associated with hyperkinesia of the apical region that resolves spontaneously. Case report: 78–year–old female affected by cerebral atrophy, leukoencephalopathy, cognitive impairment, behavior disorders. Reported episode of loss of consciousness lasting several minutes, associated with spontaneously resolving tremors and left hemisome hyposthenia. When she arrived in the emergency room, the haematological tests found high troponin values. On CT brain without contrast, no evidence of alterations of the encephalic tissues referable to acute lesions, but it showed of diffuse supratentorial leukoaraiosis and widening of the cerebrospinal fluid spaces on an atrophic basis. The neurological evaluation excludes the presence of a seizure. The electrocardiogram showed diffuse negative T waves and QTc 636 ms. The coronary angiography didn’t show significant coronary arteries stenosis and the ventriculography showed normal ventricular dimensions with total akinesia of the mid segments and normokinesia of the apical region with an ejection fraction of 50%. With these findings a diagnosis of mid left ventricular Tako–tsubo (r–TTC) was made. Transthoracic color Doppler echocardiography confirmed the alterations of the left ventricular kinetics observed by ventriculography. Conclusions compared to CTT, r–TTC is associated with a lower decline in global systolic function and, as reported in the literature, there is a greater connection to neurological insults as triggering factors, such as episodes of aneurysmal subarachnoid hemorrhage, brain surgery, ischemic stroke seizures and traumatic brain injury. The underlying mechanisms are still unknown, a crucial role in catecholamine–induced cardiotoxicity, coronary microvascular dysfunction or coronary vasospasm and/or estrogen deficiency is hypothesized.

P34 TAKOTSUBO SYNDROME OR UNKNOWN MYOCARDIAL ISCHEMIA? THE ROLE OF CARDIAC MAGNETIC RESONANCE IN DIFFERENTIAL DIAGNOSIS

Abstract There are numerous clinical conditions in which symptoms and signs may overlap, among these myocardial Ischemia in the absence of obstructive coronaropathy (INOCA/MINOCA), gets into differential diagnosis with a plethora of clinical pictures such as Takotsubo syndrome, myocarditis and cardiomyopathies. In this setting, cardiac magnetic resonance has a critical discriminating role. Herein we report the clinical case of a 52–year old patient suffering from hypertension and dyslipidaemia, with a history of chest pain episodes and recent intense psychophysical stress. After symptoms exacerbation, ambulance was called, loss of conscience was witnessed, observing ventricular fibrillation, subjected to prompt DC shock. Once in Emergency room, ECG showed ST–elevation in V1, V2 and AVR for which urgent coronary angiography was performed. It surprisingly resulted negative for epicardial coronary artery disease. Moderate left ventricular dysfunction (LVEF 45%) was found on 2D ultrasound along with apex akinesia, while mild elevation myocardial necrosis enzymes was seen at blood tests. The clinical picture characterized by female sex, history of psychophysical stress, by association of chest pain, ischemic type alterations of repolarization at ECG, akinesia of the apex and the concomitant slight elevation of myocardial necrosis enzymes in the absence of epicardial coronary lesions, highly suggested Tako–Tsubo Syndrome. In order to confirm the diagnosis, cardiac MRI was performed which, unexpectedly, showed the presence of oedema on T2–weighted STIR sequences at the level of the left ventricular apex, associated to same site transmural fibrosis at post–contrast imaging sequences, thus eliciting the hypothesis of a MINOCA. After a new retrosternal pain with transient ST–elevation in V1, a IVUS – guided new coronary angiography examination was performed, resulting intoIVA diffuse coronary spasm, reduced after intravenous nitrate administration. Final diagnosis was “MINOCA complicated by primary VF‘‘ and a subcutaneous AICD implant CMR imaging by virtue of its ability to provide information about cardiac structure and function and simultaneously, to define the characterization of tissues, together with the data of dynamic coronary spasm, proved to be essential in this case to establish the diagnosis, often misunderstood, of MINOCA, hence allowing to define the best therapeutic strategy. ​

Different Types of Myocardial Injury due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron Variant.

Coronavirus disease 2019 (COVID-19) associated myocardial injury was caused by various mechanisms. We herein describe 2 cases presenting different types of myocardial injury due to Omicron variant. In both patients, diffuse reduced left ventricular (LV) wall motion in transthoracic echocardiography, electrocardiographic abnormality, and elevated myocardial enzymes were demonstrated. In addition, cardiovascular magnetic resonance (CMR) findings fulfilled the 2018 Lake Louise Criteria (LLC) for myocarditis. However, histological findings in 1 patient showed inflammatory cell infiltration with myocyte degeneration, while those in the other showed interstitial edema without inflammatory cell infiltration. Histological findings were crucial for a differential diagnosis of myocardial injury due to Omicron variant.

P268 MANAGEMENT OF ACUTE PULMONARY EMBOLISM IN THE EMERGENCY ROOM IN ELDERLY: DOES ADHERENCE TO INTERNATIONAL GUIDELINES INCREASE IN THE MOST SERIOUS CASES?

Abstract Premises Pulmonary embolism is a pathology still characterized by high mortality. Some international studies have actually shown that adherence to guidelines is generally quite low in both primary and secondary care and ranges, depending on the studies, between 40 and 60%. Purpose of the Study see if and how, in the real life of an Emergency Department, adherence to the Guidelines varies according to the severity of the acute pulmonary embolism. We understood this severity as the presence of organ damage or massive pulmonary embolism. Methods Single–center retrospective observational study, on all geriatric patients (&amp;gt;75 y) who entered our ED, where they received a diagnosis of acute PE. Enrollment began in 2016 and ended in 2019. We collected data from medical history, physical examination, laboratory tests, imaging; we calculated the characteristic scores from the diagnostic / therapeutic algorithm, both for the risk of PE (Wells, Geneva and Years), and for the presentation of the risk of mortality at 30 days (sPESI). We therefore analyzed adherence to the guidelines in three decisional turning points: 1 Correct application of the decision scores examined, which classify the patient at low, intermediate or high risk of PE, calculated with Wells and simplified Geneva score; 2 Correct administration of therapy starting from ED as suggested by the guidelines; 3 Any observation in the care area of medium intensity with careful monitoring for the subpopulation of patients with finding of right ventricular dilation or myocardial enzyme elevation (considered to be at high risk of shock and short–term mortality). Results We enrolled 248 patients, with a mean age of 83 years with female prevalence (F = 62%). Of these, 81 (32.7%) have organ damage and 86 (34.7%) have massive pulmonary embolism. Patients with organ damage received treatment with a higher adherence to the guidelines (68%) than those who did not have organ damage (51%) in a statistically significant way (p &amp;lt; 0.01). Patients with massive pulmonary embolism received treatment with a higher adherence to the guidelines (69 %) than those with peripheral pulmonary embolism (50%) in a statistically significant way (p &amp;lt; 0.005). Conclusions The study suggests that patients with organ damage or massive pulmonary embolism are more likely to receive treatment in the emergency room with greater compliance with international guidelines.

P273 MANAGEMENT OF ACUTE PULMONARY EMBOLISM IN GERIATRIC PATIENTS IN THE EMERGENCY ROOM: DOES ADHERENCE TO INTERNATIONAL GUIDELINES REDUCE IN ATYPICAL SYMPTOMS?

Abstract Purpose of the Study Evaluate if and how, in the real life of an Emergency Department, adherence to the Guidelines varies according to the presence of atypical symptoms. We understood dyspnoea, chest pain, signs and symptoms of deep vein thrombosis and syncope as typical symptoms. As atypical symptoms all the others (low–grade fever, vertigo …) Methods Single–center retrospective observational study on all geriatric patients (&amp;gt;75 y) who entered our ED, where they received a diagnosis of acute PE. Enrollment began in 2016 and ended in 2019. We collected data from medical history, physical examination, laboratory tests, imaging; we calculated the characteristic scores from the diagnostic/therapeutic algorithm, both for the risk of PE (Wells, Geneva and YEARS), and for the presentation of the risk of mortality at 30 days (sPESI). We then analyzed adherence to the guidelines in three decision turning points: 1 Correct application of the decision scores examined, which classify the patient at low, intermediate or high risk of PE, calculated with Wells and simplified Geneva score; 2 Correct administration of therapy starting from ED as suggested by the guidelines; 3 Any observation in the care area of medium intensity with careful monitoring for the subpopulation of patients with evidence of right ventricular dilation or myocardial enzyme elevation (considered to be at high risk of shock and short–term mortality). Results We enrolled 248 patients, with a mean age of 83 years with female prevalence (F = 63%). Of these, only 17 with atypical symptoms and 231 with typical symptoms. The vital signs were comparable in the two groups with no statistically significant difference (p &amp;gt; 0.05). Long–term outcomes such as mortality, need for hospitalization, hospitalization in intensive care and length of stay in hospital are also comparable results with no statistically significant difference (p &amp;gt; 0.05). However, adherence to international guidelines was statistically significantly lower in patients with atypical symptoms (33%) than in patients with typical symptoms (59%) (p &amp;lt; 0.05). Conclusions The study suggests that patients with atypical symptoms are more likely to have reduced adherence to international guidelines, most likely due to diagnostic delay.

Nab-paclitaxel plus sintilimab as second-line therapy for advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (G/GEJA): Preliminary results from an open-label, single-arm, phase 2 study.

293 Background: Anti-PD-1 antibody showed some efficacy but was not superior to mono-chemotherapy in the second line (2L)-treatment of advanced or metastatic G/GEJA. The combination of chemotherapy and anti-PD-1 antibody has been demonstrated to have a synergistic effect. Nab-paclitaxel (nab-PTX) was one of the most common used 2L-regimens in Asia. Therefore, we aimed to assess efficacy and safety of nab-PTX plus sintilimab in patients (pts) with advanced G/GEJA in this study. Methods: This was an open-label, single-arm, phase 2 study undertaken at the National Cancer Center of China. Eligible patients were aged 18 to 75 years old with histological or cytological diagnosis of G/GEJA, had an ECOG PS of 0 or 1 and measurable disease according to the RECIST v 1.1 after 1L-chemotherapy with fluoropyrimidine and platinum. Patients received nab-PTX (125mg/m2, d1 &amp; d8, ≤ 6 cycles) and sintilimab (200mg, d1, ≤ 2 years) every 3 weeks. The primary endpoint was objective response rate (ORR). The threshold 2L-therapy ORR was set to 13% and the expected ORR was 30%. Results: From Nov 4, 2019, to Sep 15, 2021, 36 pts were enrolled and 31 pts were eligible for response assessment. Median age was 58y and 58.1% were men. Median follow-up time was 7.8 months (95% CI 3.299-12.301). ORR was 41.9%. One patient (pt) achieved complete response and 12 pts acquired partial response. Disease control rate was 83.9%. Median progression free survival was 5.2 months (95%CI 3.556-6.848). The most common treatment-related adverse events (TRAEs) of grade 3-4 were neutropenia (19.4%), leukopenia (9.7%), aspartate aminotransferase increased (9.7%), thrombocytopenia (3.2%) and fatigue (3.2%). No treatment-related deaths occurred. The potential immune-related adverse events (irAEs) were hypothyroidism (3 pts [9.7%]), pneumonia (1 pt [3.2%]), myocardial enzyme elevation without any syndrome (1 pt [3.2%]) and isolated ACTH deficiency (1 pt [3.2%]). Most of the potential irAEs were grade 1 or 2. Only one patient developed grade 3 colitis. Furthermore, 3 pts (9.7%) with diabetes developed hyperglycemia of grade 3 and 1 pt (3.2%) endured acute myocardial infarction who had a history of coronary heart disease. Conclusions: Second-line nab-PTX plus sintilimab showed promising anti-tumour activity with a manageable safety profile in pts with advanced or metastatic G/GEJA preliminarily. These results warrant further accrual and evaluation. This study is still recruiting. Clinical trial information: NCT04140318. Research Sponsor: Innovent Biologics and CSPC Ouyi Pharmaceutical Co. Ltd. Clinical trial information: NCT04140318.

Changes of Electrocardiogram and Myocardial Enzymes in Patients with Intracerebral Hemorrhage.

Purpose Cardiac complications are common in patients with spontaneous intracerebral hemorrhage (ICH). The present study is aimed at observing the incidence of cardiac complications after ICH, so as at improving the understanding of the relationship between cardiac complications and ICH. Methods This is a retrospective study on analyzing electrocardiogram (ECG) and serum myocardial enzyme of 208 patients with ICH admitted to a tertiary hospital from 2018 to 2019. For each patient, demographics, medical history, clinical presentation, ECG, serum myocardial enzyme, and head CT on admission were reviewed. Mortality was noted. Results Among the 208 patients, 145 (69.71%) had one or more ECG abnormalities. The top three abnormalities were corrected QT interval (QTc) prolongation 52 (25%), ST depression 48 (23.08%), and T wave inversion 38 (18.27%). One hundred and thirty-nine patients (66.83%) had increased serum levels of at least one kind of myocardial enzyme, which were high-sensitive cardiac troponin T (hs-cTnT) 79 (37.98%), lactic dehydrogenase (LDH) 80 (38.46%), creatine kinase (CK) 57 (27.40%), and creatine kinase-myocardial subfraction (CKMB) 57 (27.40%). The logistic regression analysis showed the following: secondary intraventricular hemorrhage (SIVH) (odds ratio (OR) 5.32; 95% confidence interval (CI) 2.55–11.08; p < 0.001) and hematoma volume > 30 ml (OR 3.81; 95% CI 1.86–7.81; p < 0.001) were independent predictive factors of QTc prolongation; thalamus location (OR 5.79; 95% CI 1.94–17.28; p < 0.05), hematoma volume > 30 ml (OR 24.187; 95% CI 3.14-186.33; p < 0.05), insular involvement (OR 19.08; 95% CI 5.77-63.07; p < 0.001), and SIVH (OR 2.62; 95% CI 1.69-5.86; p < 0.05) were independent predictive factors of ST depression; insular involvement (OR 2.90; 95% CI 1.12–7.50; p < 0.05) and hematoma volume > 30 ml (OR 1.98; 95% CI 1.06–3.70; p < 0.05) were independent predictive factors of increase of CK; Glasgow Coma Scale (GCS) (OR 0.86; 95% CI 0.78–0.98; p < 0.05) and insular involvement (OR 5.56; 95% CI 1.98–15.62; p < 0.05) were independent predictive factors of increase of CKMB; SIVH (OR 2.05; 95% CI 1.07–3.92; p < 0.05) was independent predictive factor of increase of LDH; age (OR 1.03; 95% CI 1.01–1.06; p < 0.05), blood glucose on admission (OR 1.10; 95% CI 1.01–1.20; p < 0.05), and history of antiplatelet drug use (OR 3.50; 95% CI 1.01–12.12; p < 0.05) were independent predictive factors of hs-cTnT. All the injury indexes were not related to in-hospital mortality. Conclusion The study suggests that insular involvement, hematoma volume > 30 ml, and SIVH are the strongest risk factors for ECG abnormalities and elevated myocardial enzymes after ICH followed which are the risk factors such as GCS, age, admission blood glucose, and ICH location in the thalamus.

Giant R waves on electrocardiogram in children with asphyxia after cardiopulmonary resuscitation

Abstract Introduction: Giant R waves on electrocardiogram (ECG) in pediatric patients is extremely rare. The present case report explores the giant R wave ECG characteristics and clinical features of children with asphyxia after cardiopulmonary resuscitation. Patient concerns: Two children presented with suffocation due to drowning and foreign body inhalation. Cardiopulmonary resuscitation was performed, and the children were admitted to the hospital. Diagnosis: On the day of admission, the two children were in a deep coma, with decreased blood pressure, elevated myocardial enzymes and glucose, and metabolic acidosis. However, ECG examination showed no obvious abnormalities. On the day after admission, the children experienced frequent convulsions. The ECG showed the features of giant R waves from three consecutive ECG readings. Interventions: Treatment measures during hospitalization included tracheal intubation assisted ventilation, ice cap to protect the brain to reduce basal brain metabolism, anti-infection, dehydration, lower intracranial pressure, correction of acidosis, adjustment of glucose levels, sedation, analgesia, normal saline to supplement blood volume and protect liver function. Outcomes: The giant R waves on ECG persisted until the children passed away three days after admission. Conclusion: Giant R waves on ECG in children with asphyxia after cardiopulmonary resuscitation may be related to the large release of catecholamines, which results in myocardial injury. Giant R waves on ECG indicates a serious illness and poor prognosis of the patient. In addition, giant R waves on ECG may be misdiagnosed as other arrhythmias and needs to be carefully differentiated.

Review of cardiovascular involvements in COVID-19

Background: A spectrum of cardiovascular pathologies occurs in patients with COVID-19 and increases the risk of mortality. Risk of mortality is also heightened in cardiovascular disease patients who contact COVID-19.Methodology: Online search for the keywords in PubMed, Medline, Embase, Google scholar was done. Relevant research articles yielded from the searches were reviewed.Results: the searches yielded a total of 172 results, out of which 111 were reviewed. Cardiac involvement was found in 70.6% COVID-19 patients: tachycardia (19%), electrocardiography abnormalities (22%), echocardiography abnormalities (57%), elevated myocardial enzymes (53%), and acute cardiac injury (9%). Eight percent of patients with acute cardiac injury were aged &gt;60 years; 87.5% of them had ≥2 underlying comorbidities (hypertension, diabetes mellitus, cardiovascular diseases, chronic obstructive pulmonary disease, and chronic kidney disease). Novel coronavirus pneumonia was much more severe in the patients with acute cardiac injury than in patients with non-definite acute cardiac injury (P&lt;0.001). Multivariate analyses showed that C-reactive protein (CRP) levels, old age, novel coronavirus pneumonia severity, and underlying comorbidities were the risk factors for cardiac abnormalities in patients with COVID-19.Conclusion: Besides its prominent expression at the level of the respiratory apparatus, COVID-19 is also characterized by a substantial degree of cardiovascular involvement, both in terms of deterioration of pre-existing conditions, and as the effect of inflammation-facilitated acute events. They include ischemic and inflammatory heart disease, ventricular arrhythmias, conduction disturbances, thrombotic events at the level of the lungs, systemic activation of the coagulation cascade and disseminated intravascular coagulation.

Regorafenib plus PD-1 inhibitors in Chinese patients with microsatellite stable/mismatch repair proficient metastatic colorectal cancer: A real-world study.

e15585 Background: A previous phase 1b trial has shown encouraging efficacy of regorafenib plus nivolumab in patients with microsatellite stable/mismatch repair proficient (MSS/pMMR) metastatic colorectal cancer (mCRC). We aimed to evaluate the efficacy and safety of this regimen in Chinese patients in the real world. Methods: We retrospectively identified patients with MSS/pMMR mCRC who received at least one dose of programmed cell death-1 (PD-1) inhibitors plus regorafenib from 5/2019 to 2/2021 in 10 Chinese medical centers. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and the safety. Results: Fifty-two patients were identified. Liver metastases were presented in 35 patients (67%). A total of 48 patients (92%) received regorafenib plus a PD-1 inhibitor as the third or later line treatment. At the data cut-off, 11 patients (21%) were still on treatment. Other patients terminated treatment because of progressive disease (45%), treatment-related adverse events (TRAEs) (14%) or treatment-unrelated deaths (6%). The median treatment cycle was 3 (range, 1-18). At a median follow-up of 4.9 months, the median OS was 17.3 months (95% CI, 10.2-NR) and the median PFS was 3.1 months (95%CI, 2.5-6.0). Baseline liver metastases were associated with inferior PFS (2.7 versus 6.3 months, p &lt;0.05), but not OS (17.3 months versus NR, p =0.6). Among 38 patients evaluable for response, two patients (5%) achieved partial response, and 17 patients (45%) experienced stable disease as the best response. The DCR was 50% (95%CI, 5.0-NR) and was similar among different PD-1 inhibitors (Table). TRAEs were observed in 30 patients (58%). Fatigue (21%), hand-foot syndrome (19%) and rash (13%) were the most common TRAEs. Eight patients (15%) experienced grade 3-4 TRAEs, including rash (n=3), hand-foot syndrome (n=2), hypertension (n=1), myocardial enzyme elevation (n=1) and visual field loss (n=1). No treatment-related death occurred. Conclusions: The combination of regorafenib plus PD-1 inhibitors was generally tolerated and exhibited potential benefit in terms of OS and DCR. The presence of baseline liver metastases was predictive for shorter PFS but requires further investigation. Disease control rate of different PD-1 inhibitors.[Table: see text]

Toripalimab with nab-paclitaxel/gemcitabine as first-line treatment for advanced pancreatic adenocarcinoma: Updated results of a single-arm, open-label, phase Ib/II clinical study.

e16213 Background: Currently nab-paclitaxel/gemcitabine (AG) is the standard first-line treatment for advanced pancreatic ductal adenocarcinoma (aPDAC), which is still needed to improve. The phase Ib/II study aiming to evaluate safety and efficacy of AG plus toripalimab, an anti-PD-1 monoclonal antibody, showed well tolerability and encouraging efficacy in aPDAC patients (preliminary data presented at 2020 ASCO). Here, we updated new results of this study. Methods: This was a single-arm, open-label, phase Ib/II clinical trial of AG with toripalimab as first-line treatment for aPDAC. Patients received toripalimab (240mg, Q3W), combined with AG (nab-paclitaxel 125 mg/m2, d1, d8 plus gemcitabine 1000 mg/m2, d1, d8) until the disease progresses/unacceptable toxicity or receiving toripalimab maintenance treatment. The primary objectives were safety and OS; the secondary objectives were ORR, DCR and PFS. Predictive biomarkers including MMR protein and PD-L1 expression, the tumor mutation burden (TMB) based on next-generation sequencing, genomic alteration signatures and the number of TILs were evaluated. Results: At data cutoff (Feb 3, 2021), 20 chemotherapy naïve aPDAC patients (female: 65.0%, median age: 55.5 years) with ECOG PS ≤ 2 were enrolled. Of the 17 evaluable patients, the ORR was 35.3%, the DCR was 82.4%, including 5 patients with PR and 1 patient with CR, respectively. 12 patients were alive and the study treatments for 9 patients were still ongoing. Median PFS was 5.0 months (95% CI：4.216-5.784), the 6-month PFS rate was 60%; median OS was 14.0 months (95% CI：9.445-18.555), the 1-year OS rate was 80%. 2 cases of pseudoprogression were observed. The most frequent treatment related adverse events were ALT elevation (35.0%), leukocytopenia (30.0%) metabolic disorder (25.0%) and hypothyroidism (25.0%). 4 patients (20.0%) experienced grade 3/4 TRAE (including myocardial enzyme elevation, neutropenia, vomiting and nausea). In the biomarker analysis, all patients were MMR-proficient status; 14 patients were evaluated for PD-L1 expression compared with PD-L1 negative cases (n = 5), PD-L1 positive cases (n = 9) did not show higher RR or longer PFS, responses were observed in both groups. 10 patients were investigated for NGS, 2 patients with TMB &gt; 10 Muts/Mb, the most frequently mutated genes were KRAS (90%), TP53 (90%) and ARID1A (20%). Conclusions: The updated results of this phase Ib/II study provided preliminary evidence that toripalimab in combination with AG has a manageable safety profile consistent with known safety profile for each agent alone and demonstrates signals of clinical activity. The correlation between biomarkers with clinical efficacy are under investigation. The results supported ongoing combined treatment in aPDAC patients. Clinical trial information: ChiCTR2000032293.