Asymptomatic Elevation Research Articles

A prospective analysis of the efficacy and safety of ethacizine during premature atrial contractions and premature ventricular contractions

Abstract Background Ethacizine, a class Ic antiarrhythmic agent, is prescribed for managing severe or refractory supraventricular and ventricular arrhythmias, including premature atrial (PACs) and ventricular contractions (PVCs). Despite its use, there is a lack of substantial research exploring the therapeutic effects of ethacizine at present. Purpose The study evaluated the efficacy and safety of ethacizine in addressing PACs and PVCs, in cases where other antiarrhythmic medications proved ineffective. Methods We performed a prospective analysis of ethacizine treatment (50 mg. b.i.d.) for early (30-45 days) and late periods (150-210 days), in male (n=58; 59.2%) and female (n=40; 40.8%) patients aged ≥ 18 years (18-72 y.o; mean age 45 years), with 46 cases of PACs and 52 cases of PVCs, who had previously been treated with another antiarrhythmic medication (bisoprolol, metoprolol, sotalol, verapamil, amiodarone, or propafenone) and had not achieved the target rate of extrasystoles (≤1000/24h). Results The findings reveal a substantial decrease in the mean parameters of PACs during both, the early period (initial 6877 ± 2432, following 761 ± 341); (88,9%); t([45]) = [13,336], p = [< .001) and the late period (initial 6877 ± 2432, following 574 ± 294); (91,7%); t([45]) = [15,124], p = [< .001). The quantitative reduction in PACs reached a maximum of 93.8% in the early period (19406 PACs □ 1211 PACs) and 94.3% in the late period (19406 PACs □ 1105 PACs). The mean parameters of PVCs in the early period experienced a significant reduction (initial 3205 ± 1145, following 550 ± 194); (82,8%); t([51]) = [8,284], p = [< .001). Similarly, the mean PVC values in the late period exhibited a noteworthy decrease (initial 3205 ± 1145, following 490 ± 181); (84,8%); t([51]) = [8,553], p = [< .001). For PVCs, the maximum effect observed in the early period was 94.8% (18929 PVCs □ 989 PVCs), and in the late period, it reached 95% (18929 PVCs □ 950 PVCs). The target rate in the late period (≤1000/24h.) for PACs reached 89%, and for PVCs - 86% (Figure 1). Adverse effects were noted in a mere four subjects (4%). These events manifested as 2nd-degree AV block (Mobitz 1), sustained ventricular tachycardia, asymptomatic nonsustained polytopic ventricular tachycardia, and asymptomatic transient ST-segment elevation observed through 24-hour ECG holter monitoring. Conclusion A prospective study on ethacizine treatment (50 mg. b.i.d.) confirmed its effectiveness and safety in reducing PACs and PVCs. It demonstrated a sustained reduction in extrasystole occurrences for an extended period, achieving the target rate with minimal side effects. Ethacizine merits consideration for addressing extrasystolic arrhythmia, particularly in cases where other antiarrhythmic medications prove ineffective.Results of the study

The safety of standardized management of suspected cardiovascular immune-related events in patients treated by immunecheckpoints inhibitors

Abstract Background Immune checkpoint inhibitors (ICIs) treatment carries a risk of immune-related adverse events (irAEs), including cardiovascular (CV) events. Current guidelines recommend troponin testing to detect early CV irAEs, especially myocarditis, prompting hospital admission. However, high volumes might hinder hospital admission for all suspected CV irAEs patients. Purpose To assess the safety of standardized management in outpatients with suspected irAEs. Methods A prospective single-center cohort study was conducted, including all adults referred to our unit for suspected CV irAEs. Patients exhibiting CV symptoms, receiving double ICIs, or showing ECG changes were referred to cardiology or intensive care based on severity. Patients with no CV symptoms or ECG changes, on single ICI therapy, and no other immune disorder were assessed in a day stay within 8 working days. Patients underwent serial serum testing, ECG, transthoracic echocardiogram, and cardiac magnetic resonance imaging (cMRI) and were assessed by a multidisciplinary team (MDT) including cardiology and internal medicine specialists. Coronary artery imaging and endomyocardial biopsy were performed when deemed necessary (Figure 1). The primary endpoint was CV mortality at 30 days after referral. Secondary endpoints included identifying factors associated with the diagnosis of CV irAEs at referral. Events were adjudicated by a panel of experts (FC, MM, SH) who reviewed the MDT's weekly meeting conclusions. Results 175 patients were enrolled from March 2022 to October 2023; 40 (22.89%) were male, median age 61 (IQR 48.0-72.0) years. 146 (83.4%) were seen in the outpatient clinic. No CV deaths occurred within the initial 30 days. 95 patients (54.1%) had CV irAEs at referral, including 72 (41.1%) with myocarditis; 10 (5.7%) with acute coronary syndromes; 9 (5.1%) with pericarditis; 7 (4.0%) with heart failure; 4 (2.3%) with high-degree conduction or ventricular arrhythmias; and 1 (0.6%) with Tako-Tsubo. 8 (4.6%) had a combination of CV irAEs. The majority of patients admitted to the hospital had CV irAEs (24, 82.7%). On multivariable regression analysis(Figure 2), CV or muscle symptoms(OR 2.677 [CI 1.207-5.937], p=0.015), prior CV disease history(OR 3.668 [CI 1.486-9.057], p=0.0048), and abnormal ECG (OR 2.855 [CI 1.074-7.589], p=0.035) remained associated with CV irAEs at referral. Including global longitudinal strain (GLS) in the model, we identified prior CV disease history. (OR 7.011 [CI 2.217-22.167], p=0.0009) and GLS <16% (OR 2.774 [CI 1.07-7.17], p=0.035) as significant. Conclusions We demonstrate the safety of a standardized outpatient management approach for most patients referred for suspected CV irAEs, mainly triggered by asymptomatic elevation of troponin. No patient experienced CV death at 30 days. When suspecting a CV irAEs, CV or muscle symptoms, previous history of CV disease, and abnormal ECG should prompt speedy assessment given the higher likelihood of CV irAEsFigure 1

The spectrum of rippling muscle disease.

Rippling muscle disease (RMD) is a rare disorder of muscle hyperexcitability. It is characterized by rippling wave-like muscle contractions induced by mechanical stretch or voluntary contraction followed by sudden stretch, painful muscle stiffness, percussion-induced rapid muscle contraction (PIRC), and percussion-induced muscle mounding (PIMM). RMD can be hereditary (hRMD) or immune-mediated (iRMD). hRMD is caused by pathogenic variants in caveolin-3 (CAV3) or caveolae-associated protein 1/ polymerase I and transcript release factor (CAVIN1/PTRF). CAV3 pathogenic variants are autosomal dominant or less frequently recessive while CAVIN1/PTRF pathogenic variants are autosomal recessive. CAV3-RMD manifests with a wide spectrum of clinical phenotypes, ranging from asymptomatic creatine kinase elevation to severe muscle weakness. Overlapping phenotypes are common. Muscle caveolin-3 immunoreactivity is often absent or diffusely reduced in CAV3-RMD. CAVIN1/PTRF-RMD is characterized by congenital generalized lipodystrophy (CGL, type 4) and often accompanied by several extra-skeletal muscle manifestations. Muscle cavin-1/PTRF immunoreactivity is absent or reduced while caveolin-3 immunoreactivity is reduced, often in a patchy way, in CAVIN1/PTRF-RMD. iRMD is often accompanied by other autoimmune disorders, including myasthenia gravis. Anti-cavin-4 antibodies are the serological marker while the mosaic expression of caveolin-3 and cavin-4 is the pathological feature of iRMD. Most patients with iRMD respond to immunotherapy. Rippling, PIRC, and PIMM are usually electrically silent. Different pathogenic mechanisms have been postulated to explain the disease mechanisms. In this article, we review the spectrum of hRMD and iRMD, including clinical phenotypes, electrophysiological characteristics, myopathological findings, and pathogenesis.

A study on correlation of liver function tests and outcome in patients of dengue

Dengue, a mosquito-borne viral disease, presents a significant public health threat, particularly in tropical and subtropical regions. This study aims to assess the correlation between elevated serum aminotransferases and dengue severity, focusing on patients at a tertiary care center. The liver is affected to varying degrees in dengue patients, from asymptomatic enzyme elevation to severe hepatitis. The study found that elevated SGOT levels correlate with more severe symptoms, including prolonged fever, abdominal pain, and bleeding manifestations.

EXTRAHEPATIC MANIFESTATIONS IN PATIENTS WITH ACUTE HEPATITIS E – PAZARDZHIK, BULGARIA 2014 – 2022

BACKGROUND: Hepatitis E is a global health issue, only partially understood. Bulgarian record started in 2019 and data is not sufficient. AIM: This research aims to analyze extrahepatic manifestation of acute hepatitis E in patients with hepatitis E from Pazardzhik region, between 2014 – 2022. MATERIALS AND METHODS: The analysis includes 247 patients with acute hepatitis E, treated at the Department of Infectious Diseases of Pazardzhik Multiprofile Hospital for Active Treatment, Bulgaria between 2014 – 2022. The methodology includes clinical observation, laboratory tests and medical imaging. The diagnosis was established by serological /ELISA for anti-HEV IgM, IgG detection/and molecular-biological tests /RT-PCR for HEV RNA detection/. RESULTS: We observed extrahepatic manifestations in 19% (47/247) of the cases. In 60% (28/47) comorbidities were present, and 9% (4/47) were with underlying acute/chronic coinfection with another hepatotropic virus. Thrombocytopenia was found in 83% (39/47) of the patients; asymptomatic creatine kinase elevation – in 13% (6/47), acute pancreatitis – in 9% (4/47), transitory renal impairent – in 6% (3/47); 2% (1/47) had Guillain-Barré syndrome (GBS), 2% (1/47) – arrhythmia and 13% (6/47) – multiorgan involvement. While 91% (43/47) of the patients recovered, in 9% (4/47) the outcome was fatal. CONCLUSION: Extrahepatic manifestations might prevail, potentially delaying diagnosis of HEV-infection. Symptoms associated with comorbidities might also impede the final diagnosis. A diagnostic algorithm is needed to enhance the accurate diagnosis of HEV in patients with dubious symptoms.

IgG4 Sclerosing Cholangitis: Entity Rarely Described in Children

IgG4-related sclerosing cholangitis (IgG4-SC) is known in the adult patients as a steroid-responsive biliary disease, frequently associated with autoimmune pancreatitis; The diagnosis of IgG4-SC may be difficult to differentiate from primary sclerosing cholangitis (PSC) or cholangiocarcinoma; This entity is been described in the absence of pancreatic implication. It is defined by high level of serum IgG4 in contrast to primary sclerosing cholangitis. It’is morphologically characterized by dense lymphoplasmacellular infiltration, particularly IgG4+ plasma cells and CD4+ T cells and extensive fibrosis in bile duct. In patients with IgG4-related sclerosing cholangitis, response to steroid therapy is high; in patients with PSC corticosteroid therapy is unsuccessful. An Early recognition of IgG4-SC can save patients from potential harmful and unnecessary surgical interventions. In the literature, cholangiocarcinoma in patients with IgG4- related sclerosing cholangitis was not described, whereas cholangiocarcinoma develops in up to 10-30% of patients with PSC. We present the case of a 3 years old child with features of sclerosing IgG4 cholangitis with asymptomatic elevation in liver enzymes, bile duct strictures on imaging, characteristic pathology findings, elevated serum IgG4, without signs of pancreatic involvement, and excellent response to corticosteroids. Pediatric gastroenterologists and hepatologists, as well as pediatric hepatopathologists, need to be aware of IgG4-SC as a disease entity.

Immune Checkpoint Inhibitors in Cancer Treatment and Incidence of Pancreatitis.

Immune checkpoint inhibitors (ICIs) are an approved therapy for the management of various advanced neoplasms. Limited reviews focus on the influence of this therapy resulting in pancreatitis. This review discusses the relationship between ICIs and their effects on the pancreas, including the incidence of pancreatitis, immunotherapy, programmed cell death 1 (PD-1) receptors, driver mutations, programmed death ligand 1 (PD-L1), and immune-related adverse events. Additionally, it focuses on the clinical presentations, diagnosis, case studies, and mechanisms by which ICIs activate different pathways to cause pancreatitis. We conducted a comprehensive literature search using PubMed, Cochrane Library, and Google Scholar databases to identify relevant studies on ICI-associated pancreatitis. The review explores the incidence and epidemiology of ICI-induced pancreatitis, its clinical presentation, diagnostic criteria, and management strategies.The overall incidence of ICI-induced pancreatitis is estimated at 1-2%, with higher rates observed in combination therapy. Clinical presentations range from asymptomatic enzyme elevations to severe pancreatitis. Diagnosis relies on a combination of clinical symptoms, elevated pancreatic enzymes, and imaging findings, with MRI and endoscopic ultrasound showing promise in early detection. Management strategies include IV fluid administration, pain control, and nutritional support. The efficacy of corticosteroids remains controversial, and alternative immunosuppressants are being explored for steroid-refractory cases. Long-term monitoring is crucial due to the risk of chronic pancreatitis and pancreatic insufficiency. This review highlights the need for further research to elucidate the exact mechanisms of ICI-associated pancreatic injury, develop predictive biomarkers, and refine treatment protocols. As ICI use continues to expand, a thorough understanding of this adverse event is essential for optimizing patient care and outcomes in cancer immunotherapy.

A PHASE 1 FIRST-IN-HUMAN STUDY OF THE MCL-1 INHIBITOR AZD5991 IN PATIENTS WITH RELAPSED/REFRACTORY HEMATOLOGIC MALIGNANCIES.

AZD5991, a human MCL-1 inhibitor, was assessed for safety, tolerability, pharmacokinetics (PK), and antitumor activity as monotherapy and in combination with venetoclax in patients with relapsed or refractory (R/R) hematologic malignancies. In the monotherapy cohort (n=61), patients with hematologic malignancies received AZD5991 intravenously in escalating doses either once or twice weekly, following intrapatient dose escalation, on a 3-week cycle. In the combination cohort (n=17), patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) received escalating doses of AZD5991 and venetoclax on either a 3-week or 4-week cycle. Primary objectives were safety and maximum tolerated dose; secondary objectives included plasma PK and antitumor activity. The most common (≥30%) adverse events (AEs) were diarrhea (59.0%), nausea (55.1%), and vomiting (47.4%). Four deaths occurred due to AEs: cardiac arrest, sepsis, tumor lysis syndrome (TLS), and acute respiratory failure; only TLS was related to AZD5991. Dose-limiting toxicities occurred in 5 patients. Three patients with MDS achieved an objective response: 1 marrow complete remission (mCR) without hematologic improvement, 1 partial remission with AZD5991 monotherapy, and 1 mCR with AZD5991+venetoclax. Asymptomatic elevations of troponin I or T were observed in 8 (10.3%) patients. Post hoc retrospective analysis revealed elevated troponin T in 14/31 patients before any AZD5991 dose and in 54/65 patients after any AZD5991 dose at or after cycle 1. There were no associations between elevated troponin and cardiovascular risk factors. Treatment with AZD5991 was associated with high incidence of laboratory troponin elevation and a low overall response rate.

49/f with asymptomatic elevations of GPT and GGT

49/f with asymptomatic elevations of GPT and GGT

Cabozantinib in patients with unresectable and progressive metastatic phaeochromocytoma or paraganglioma (the Natalie Trial): a single-arm, phase 2 trial

Metastatic phaeochromocytomas and paragangliomas (MPPGs) are orphan diseases. Up to 50% of MPPGs are associated with germline pathogenic variants of the SDHB gene. These tumours and many non-familial MPPGs exhibit a phenotype that is characterised by abnormal angiogenesis. We aimed to assess the activity and safety of cabozantinib, an antiangiogenic multi-tyrosine kinase inhibitor, in patients with MPPGs. The Natalie Trial is a single-arm, phase 2 clinical trial being conducted at The University of Texas MD Anderson Cancer Center (Houston, TX, USA). Patients aged 18 years or older with histologically confirmed, progressive, and unresectable MPPGs, with an Eastern Cooperative Oncology Group performance status of 0-2, were treated with oral cabozantinib 60 mg/day. The primary endpoint was the investigator-assessed overall response rate per the Response Evaluation Criteria in Solid Tumours version 1.1 criteria. All outcomes were assessed in all evaluable participants who received any amount of study treatment. The trial is registered with ClinicalTrials.gov (NCT02302833) and is active but not recruiting. From March 10, 2015, to May 11, 2021, 17 patients (13 male participants and four female participants) were enrolled. The median follow-up was 25 months (IQR 18-49). The overall response rate was 25·0% (95% CI 7·3-52·4; four of 16 patients). Seven grade 3 adverse events were reported in six patients, including single cases of hand-and-foot syndrome, hypertension, rectal fistula, QT prolongation, and asymptomatic hypomagnesaemia, and two cases of asymptomatic elevations of amylase and lipase. There were no grade 4 adverse events and no patient died on-study. Cabozantinib shows promising activity in patients with MPPGs. Team NAT Foundation, Margaret Cazalot, and Clarence P Cazalot.

Dengue-related acute liver failure-A scoping review.

Infection by dengue virus is common in tropical countries. Hepatic involvement in dengue can range from asymptomatic elevation of transaminases to life-threatening acute liver failure (ALF). Dengue-related ALF (DALF) is responsible for significant morbidity and mortality, especially in Southeast Asia. However, there is a scarcity of literature on DALF, necessitating a thorough examination of its clinical determinants and management strategies. All relevant studies related to DALF were reviewed until December 2023. Case reports, case series and studies reporting ALF in dengue infection were included. Demographics, clinical profiles, management and outcomes of DALF cases were analyzed, which revealed a predominance of DALF incidence in pediatric patients (1.1% to 15.8%) and an upward trend over the years, particularly in India. The proportion of ALF cases attributable to dengue was also higher among pediatric ALF patients (6.7% to 34.3%). Age ≤ 40years, persistent nausea, vomiting and elevated serum bilirubin and alkaline phosphatase (ALP) with aspartate aminotransferase (AST) > 1000IU/mL within the first five days of illness, more than 10% of atypical lymphocytes in peripheral blood, platelet count of < 50,000/cu·mm, severe hepatitis at presentation and baseline model for end-stage liver disease (MELD) > 15 were the risk factors for the development of DALF. Histopathological features of DALF included multi-lobular hepatic necrosis, steatosis and occasional cholestasis. Mortality in DALF ranged from 0% to 80%; admission pH and lactate strongly predicted mortality, while mortality was found to be significantly higher in patients with cirrhosis. N-Acetyl cysteine (NAC) has been used as a treatment modality with varying results. There is limited evidence regarding the use of extra-corporeal support systems, while candidate selection for liver transplantation (LT) in DALF remains poorly defined.

Impact of statins in the liver: A bane or a boon?

Treatment of hypercholesterolemia with statins is considered one of the cornerstones in the management of atherosclerotic cardiovascular diseases. Statins exert their hypolipidemic effects by inhibiting HMG-CoA reductase, the key enzyme in cholesterol biosynthesis. Beyond cholesterol reduction, statins exhibit pleiotropic effects, including anti-inflammatory, antioxidant, and antiproliferative actions, making them valuable in mitigating atherosclerotic and non-atherosclerotic diseases. Though concerns of hepatotoxicity have been associated with the use of statins, extensive evidence suggests that the risk of statin-induced liver injury (SILI) is rare, with an incidence of &lt;1%. Hepatic adverse effects include reversible asymptomatic transaminase elevation (most frequent), hepatitis, cholestasis, and rarely acute liver failure. While hepatotoxicity concerns should not be dismissed, the evidence overwhelmingly supports the safety of statins. Contrary to the myth of statin hepatotoxicity, real-world data and extensive research emphasize the safety and benefits of statins. They are therapeutic in various liver-related conditions, mainly non-alcoholic fatty liver disease. This scientific review aims to provide a comprehensive overview of statins, shedding light on their mechanism of action, hepatotoxicity concerns, and therapeutic potential in various liver-related conditions.

Metabolomic profiling reveals key metabolites associated with hypertension progression.

Pre-hypertension is a prevalent condition among the adult population worldwide. It is characterized by asymptomatic elevations in blood pressure beyond normal levels but not yet reaching the threshold for hypertension. If left uncontrolled, pre-hypertension can progress to hypertension, thereby increasing the risk of serious complications such as heart disease, stroke, kidney damage, and others. The precise mechanisms driving the progression of hypertension remain unknown. Thus, identifying the metabolic changes associated with this condition can provide valuable insights into potential markers or pathways implicated in the development of hypertension. In this study, we utilized untargeted metabolomics profiling, which examines over 1,000 metabolites to identify novel metabolites contributing to the progression from pre-hypertension to hypertension. Data were collected from 323 participants through Qatar Biobank. By comparing metabolic profiles between pre-hypertensive, hypertensive and normotensive individuals, six metabolites including stearidonate, hexadecadienoate, N6-carbamoylthreonyladenosine, 9 and 13-S-hydroxyoctadecadienoic acid (HODE), 2,3-dihydroxy-5-methylthio- 4-pentenoate (DMTPA), and linolenate were found to be associated with increased risk of hypertension, in both discovery and validation cohorts. Moreover, these metabolites showed a significant diagnostic performance with area under curve >0.7. These findings suggest possible biomarkers that can predict the risk of progression from pre-hypertension to hypertension. This will aid in early detection, diagnosis, and management of this disease as well as its associated complications.

Statin Associated Muscular Adverse Effects.

Statins are widely used in the treatment of hyperlipidemia and in the prevention of cardiovascular diseases. However, they may induce muscular adverse effects that range from asymptomatic elevation of creatine kinase to life threatening rhabdomyolysis. The aim of the study was to describe epidemiological and clinical characteristics of patients with muscular adverse effects. We conducted a retrospective and descriptive study over a ten-year period from January 2010 to December 2019. We included all cases of statin associated muscular adverse effects notified to the Tunisian National Centre of Pharmacovigilance during this period. The study involved 22 muscular adverse effects related to statins (28% of all adverse events reported with statins during this period). Patient's mean age was 58.7 years and the sex ratio was 1.6. There were 12 cases of isolated creatine kinase elevation, 5 cases of myalgia, 3 cases of myopathy, one case of myositis and one case of rhabdomyolysis. Muscular adverse effects occurred 7 days to 15 years after starting this drug. In all cases, the statin was withdrawn after muscular adverse effects and resolution of symptoms was observed within 10 days to 18 months. In seven cases, creatine kinase persisted elevated for 18 months. Involved statins were atorvastatin, simvastatin, rosuvastatin and fluvastatin. Early recognition of muscle symptoms is required to prevent rhabdomyolysis. Further researchare needed to completely elucidate the pathophysiology of statin-induced muscular adverse effects.

ASSOCIATION COVID-19 AND LIVER INJURY : A SYSTEMATIC REVIEW

Background: Most COVID-19 patients present with typical respiratory symptoms (i.e., cough, dyspnea) and fever. However, abnormal liver function is often developed in patients with COVID-19, and liver injury has been related with severe disease. Liver damage ranges from mild asymptomatic elevation of liver enzymes to severe liver injury, while a few cases of acute liver failure have also been reported. The aim: This study aims to show association COVID-19 and liver injury. Methods: By comparing itself to the standards set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. So, the experts were able to make sure that the study was as up-to-date as it was possible to be. For this search approach, publications that came out between 2013 and 2023 were taken into account. Several different online reference sources, like Pubmed and SagePub, were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done. Result: In the PubMed database, the results of our search brought up 44 articles, whereas the results of our search on SagePub brought up 334 articles. The results of the search conducted for the last year of 2013 yielded a total 7 articles for PubMed and 111 articles for SagePub. The result from title screening, a total 4 articles for PubMed and 46 articles for SagePub. In the end, we compiled a total of 10 papers. We included five research that met the criteria. Conclusion: COVID-19-associated liver injury is caused by the cumulative effects of multiple factors, including hepatotropic SARS-CoV-2, drug-induced liver injury, hypoxic reperfusion, immune stress and inflammatory factor storms.

Impact of the ESC Cardio-Oncology Guidelines Biomarker Criteria on Incidence of Cancer Therapy–Related Cardiac Dysfunction

BackgroundThe impact of recent consensus definitions of cancer therapy–related cardiac dysfunction (CTRCD) from the European Society of Cardiology cardio-oncology guidelines on the reported incidence of CTRCD has not yet been assessed. ObjectivesThe aim of this study was to assess the: 1) cumulative incidence; 2) point prevalence during and after adjuvant therapy; and 3) prognostic value of CTRCD as defined by different asymptomatic CTRCD guideline criteria. MethodsThe cumulative incidence and point prevalence of CTRCD were retrospectively assessed in 118 patients participating in the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial. Asymptomatic CTRCD was assessed using alternative cardiac troponin (cTn) 99th percentile upper reference limits (URLs) to define cTnT and cTnI elevation. ResultsThe cumulative incidence of moderate or severe CTRCD was low (1.7%), whereas the cumulative incidence of mild asymptomatic CTRCD was higher and differed markedly according to the biomarker criteria applied, ranging from 49.2% of patients when cTnT greater than the sex-specific 99th percentile URL was used to define cTn elevation to 9.3% when sex-neutral cTnI was used. The point prevalence of CTRCD was highest at the end of anthracycline therapy (47.8%) and was driven primarily by asymptomatic cTn elevation. CTRCD during adjuvant therapy was not prognostic for CTRCD at extended follow-up of 24 months (Q1-Q3: 21-29 months) after randomization. ConclusionsMild asymptomatic CTRCD during adjuvant breast cancer therapy was frequent and driven mainly by cTn elevation and was not prognostic of subsequent CTRCD. The incidence of mild, asymptomatic CTRCD differed markedly depending on the cTn assay and whether sex-neutral or sex-dependent URLs were applied. (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy [PRADA]; NCT01434134)

The Natural History of SARS-CoV-2-Incurred Disease: From Infection to Long COVID

The coronavirus SARS-CoV-2 is the causative pathogen of the COVID-19 pandemic that has been causing global upheaval since 2019. The widespread administration of vaccines has partially deterred the spread of SARS-CoV-2, yet the virus is mutating its genome to reduce its antigenicity and evade the human herd immunity. It seems that SARS-CoV-2 will co-exist with the human population for many decades to come. While most infected individuals only experience mild to moderate symptoms, some develop severe pulmonary and systemic disease that can result in hospitalization or even death. The natural history model of SARS-CoV-2 infection has been proposed which includes three sequential stages: the early infection stage, pulmonary stage, and hyper-inflammatory stage. Recently, it has been observed that many people who recovered from an acute infection still experience persistent symptoms for weeks or months, a condition known as long COVID. Furthermore, some COVID-19 patients display escalated rates of both macro- and micro-thrombosis due to endotheliopathy. Hence, we added the thrombosis and convalescent stages to the natural history model, encompassing the entire period from early infection to long COVID. The early infection stage is characterized by symptomatic or asymptomatic elevation of viral titers. Some patients progress to the pulmonary stage characterized by opacities in chest X-rays and computed tomography. The thrombosis stage is characterized by heightened rates of pulmonary thrombosis and consistently elevated D-dimer levels. The hyper-inflammatory stage is characterized by storms of cytokines, such as IL-6, IL-17, and interferons, which is a systemic effect. In the convalescent stage, some people recover completely, while others suffer from long COVID with persistent symptoms such as fatigue, shortness of breath, or brain fog. The natural history model of SARS-CoV-2 infection can be used to elucidate treatment and care.

Troponin Elevation in Patients Undergoing Percutaneous Hepatic Perfusion for Metastatic Uveal Melanoma.

Percutaneous Hepatic Perfusion (PHP) is a liver directed regional therapy recently FDA approved for metastatic uveal melanoma to the liver involving percutaneous isolation of liver, saturation of the entire liver with high-dose chemotherapy and filtration extracorporeally though in line filters and veno-venous bypass. The procedure is associated with hemodynamic shifts requiring hemodynamic support and blood product resuscitation due to coagulopathy. To assess the cardiac safety and subsequent clinically significant sequalae of this therapy. Consecutive PHP procedures done at our center between 2010-2022 were assessed retrospectively. Cardiac risk factors, post procedural cardiac enzymes, electrocardiograms, and transthoracic echocardiograms along with 90-day cardiac outcomes were reviewed. All data were reviewed by cardio-oncologists at our institution. Of 37 patients reviewed, mean age was 63years and 57% were women. 132 procedures were performed with an average of 3.57 procedures per patient. 68.6% of patients had elevated troponin during at least 1 procedure. No patients were found to have acute coronary syndrome, heart failure, unstable arrhythmias, or cardiac death. No patients had notable echocardiographic changes. 10.8% of patients with positive troponin had asymptomatic transient electrocardiographic changes not meeting criteria for myocardial infarction. One patient had non-sustained ventricular tachycardiac intra-operatively which did not recur subsequently. Three patients died from non-cardiac causes within 90-days. There was no oncology treatment interruption, even in those with troponin elevation. In multivariable analysis, a history of hyperlipidemia was a predictor of postoperative troponin elevation. (P = .042). Percutaneous Hepatic Perfusion is safe and associated with a transient, asymptomatic troponin elevation peri-operatively without major adverse cardiac events at 90days. The observed troponin elevation is likely secondary to coronary demand-supply mismatch related to procedural hemodynamic shifts, hypotension, and anemia.

A Phase-IV Non-interventional Study to Assess Virological Effectiveness, Safety, and Tolerability of DTG-based Antiretroviral Therapy in HIV-1 Infected Indian Persons Living with HIV.

Dolutegravir (DTG) is a novel yet preferential first- and -second-line treatment for persons living with HIV (PLH). Owing to its recent introduction, DTG-based regimens have not undergone a comprehensive, systematic evaluation regarding their real-world utilization and safety profile among a sizeable Indian population. This study aimed to assess the 24 week immunovirological outcomes, anthropometric and metabolic changes, tolerability, and adverse events (AEs) of DTG-based antiretroviral (ART) regimens. A single-centre phase-IV non-interventional observational study involving 322 ART naïve and treatment-experienced PLH initiating DTG-based-regimens until October 2022 were followed up for outcomes at 24 weeks. At 24 weeks, all PLH (n = 113) in the naïve group, all PLH (n = 67) in the first-line substitution group, 93.9% PLH (n = 46) in the first-line failure group, and 95.7% PLH (n = 89) in the second-line substitution group were virologically suppressed to plasma HIV-RNA <1000 copies/mL. Virological suppression rates to plasma HIV-RNA <200 copies/mL and <50 copies/mL were consistent among PLH who received DTG as first- or second-line ART. The mean-unadjusted weight gain observed was 3.5 kg (SE: 0.330), and it was significantly higher in PLH with poorer health at baseline (either HIV-RNA ≥ 1000 copies/ml or CD4 cell count <350 cells/μL). Overall, 27.3% PLH (n = 88) gained ≥10% of their baseline body weight, corresponding to 3.7% incidence (n = 12) of treatment-emergent clinical obesity. DTG had an overall lipid-neutral effect, with an advantageous effect being observed in PLH switching from non-nucleoside analogue reverse-transcriptase inhibitors (NNRTI) or ritonavir-boosted protease inhibitors (b/PI), especially in dyslipidemic pre-treated PLH (median change in total cholesterol: 28.5 mg/dL and triglycerides: 51 mg/dL), possibly emanating from the withdrawal of the offending ART. The incidence of DTG-specific AEs, including CNS AEs, was low. Two PLH developed proximal myopathy and one developed transaminitis, warranting DTG discontinuation. Asymptomatic serum-CPK elevation and drug-induced transaminitis were seen in 25.2% (n = 27) and 3.2% (n = 10) PLH, respectively. No apparent negative effects on renal function were detected. Our results from a large Indian cohort indicate a favourable virological and metabolic response, with good tolerance of DTG-based ART at 24 weeks.

Approach and intervention in blood pressure abnormalities

Hypertension is when blood pressure (BP) is measured above the limits of what is considered normal. Almost all guidelines define hypertension as a systolic blood pressure (SBP) above 140 mmHg and a diastolic blood pressure (DBP) above 90 mmHg. Blood pressure should not be seen only as a numerical value that should be monitored and lowered when it rises. Blood pressure is an important vital sign that can provide important clues to the clinician about the patient's current condition. Long-term control of hypertension in individuals significantly reduces cardiovascular risk. In the case of hypertensive emergencies or urgent situations, antihypertensive treatment should be initiated after consideration of the approach to the recommendations. Recent observational studies suggest that pharmacologic treatment of acute and asymptomatic in-hospital BP elevations may not be beneficial and may even increase the risk of in-hospital and post-discharge complications. The patient's current clinical status and additional comorbidities should be evaluated, and attention should be paid to contraindications and drug dosage adjustments.