Multicenter, Prospective, Randomized Controlled Trial of High-Sensitivity Cardiac Troponin I-Guided Combination Angiotensin Receptor Blockade and Beta-Blocker Therapy to Prevent Anthracycline Cardiotoxicity: The Cardiac CARE Trial.

BACKGROUND: Anthracycline-induced cardiotoxicity has a variable incidence, and the development of left ventricular dysfunction is preceded by elevations in cardiac troponin concentrations. Beta-adrenergic receptor blocker and renin-angiotensin system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients receiving anthracycline chemotherapy. METHODS: In a multicenter, prospective, randomized, open-label, blinded end-point trial, patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy underwent serial high-sensitivity cardiac troponin testing and cardiac magnetic resonance imaging before and 6 months after anthracycline treatment. Patients at high risk of cardiotoxicity (cardiac troponin I concentrations in the upper tertile during chemotherapy) were randomized to standard care plus cardioprotection (combination carvedilol and candesartan therapy) or standard care alone. The primary outcome was adjusted change in left ventricular ejection fraction at 6 months. In low-risk nonrandomized patients with cardiac troponin I concentrations in the lower 2 tertiles, we hypothesized the absence of a 6-month change in left ventricular ejection fraction and tested for equivalence of ±2%. RESULTS: Between October 2017 and June 2021, 175 patients (mean age, 53 years; 87% female; 71% with breast cancer) were recruited. Patients randomized to cardioprotection (n=29) or standard care (n=28) had left ventricular ejection fractions of 69.4±7.4% and 69.1±6.1% at baseline and 65.7±6.6% and 64.9±5.9% 6 months after completion of chemotherapy, respectively. After adjustment for age, pretreatment left ventricular ejection fraction, and planned anthracycline dose, the estimated mean difference in 6-month left ventricular ejection fraction between the cardioprotection and standard care groups was -0.37% (95% CI, -3.59% to 2.85%; P=0.82). In low-risk nonrandomized patients, baseline and 6-month left ventricular ejection fractions were 69.3±5.7% and 66.4±6.3%, respectively: estimated mean difference, 2.87% (95% CI, 1.63%-4.10%; P=0.92, not equivalent). CONCLUSIONS: Combination candesartan and carvedilol therapy had no demonstrable cardioprotective effect in patients receiving anthracycline-based chemotherapy with high-risk on-treatment cardiac troponin I concentrations. Low-risk nonrandomized patients had similar declines in left ventricular ejection fraction, bringing into question the utility of routine cardiac troponin monitoring. Furthermore, the modest declines in left ventricular ejection fraction suggest that the value and clinical impact of early cardioprotection therapy need to be better defined in patients receiving high-dose anthracycline. REGISTRATION: URL: https://doi.org; Unique identifier: 10.1186/ISRCTN24439460. URL: https://www.clinicaltrialsregister.eu/ctr-search/search; Unique identifier: 2017-000896-99.

Myocardial Involvement After Hospitalization for COVID-19 Complicated by Troponin Elevation: A Prospective, Multicenter, Observational Study.

BACKGROUND: Acute myocardial injury in hospitalized patients with coronavirus disease 2019 (COVID-19) has a poor prognosis. Its associations and pathogenesis are unclear. Our aim was to assess the presence, nature, and extent of myocardial damage in hospitalized patients with troponin elevation. METHODS: Across 25 hospitals in the United Kingdom, 342 patients with COVID-19 and an elevated troponin level (COVID+/troponin+) were enrolled between June 2020 and March 2021 and had a magnetic resonance imaging scan within 28 days of discharge. Two prospective control groups were recruited, comprising 64 patients with COVID-19 and normal troponin levels (COVID+/troponin-) and 113 patients without COVID-19 or elevated troponin level matched by age and cardiovascular comorbidities (COVID-/comorbidity+). Regression modeling was performed to identify predictors of major adverse cardiovascular events at 12 months. RESULTS: Of the 519 included patients, 356 (69%) were men, with a median (interquartile range) age of 61.0 years (53.8, 68.8). The frequency of any heart abnormality, defined as left or right ventricular impairment, scar, or pericardial disease, was 2-fold greater in cases (61% [207/342]) compared with controls (36% [COVID+/troponin-] versus 31% [COVID-/comorbidity+]; P<0.001 for both). More cases than controls had ventricular impairment (17.2% versus 3.1% and 7.1%) or scar (42% versus 7% and 23%; P<0.001 for both). The myocardial injury pattern was different, with cases more likely than controls to have infarction (13% versus 2% and 7%; P<0.01) or microinfarction (9% versus 0% and 1%; P<0.001), but there was no difference in nonischemic scar (13% versus 5% and 14%; P=0.10). Using the Lake Louise magnetic resonance imaging criteria, the prevalence of probable recent myocarditis was 6.7% (23/342) in cases compared with 1.7% (2/113) in controls without COVID-19 (P=0.045). During follow-up, 4 patients died and 34 experienced a subsequent major adverse cardiovascular event (10.2%), which was similar to controls (6.1%; P=0.70). Myocardial scar, but not previous COVID-19 infection or troponin, was an independent predictor of major adverse cardiovascular events (odds ratio, 2.25 [95% CI, 1.12-4.57]; P=0.02). CONCLUSIONS: Compared with contemporary controls, patients with COVID-19 and elevated cardiac troponin level have more ventricular impairment and myocardial scar in early convalescence. However, the proportion with myocarditis was low and scar pathogenesis was diverse, including a newly described pattern of microinfarction. REGISTRATION: URL: https://www.isrctn.com; Unique identifier: 58667920.

Takotsubo Syndrome: Pathophysiology, Emerging Concepts, and Clinical Implications.

Takotsubo syndrome is a condition characterized by acute transient left ventricular systolic dysfunction, which at presentation can be challenging to distinguish from acute myocardial infarction. Although previously thought to be a benign, self-limiting condition, recent studies have confirmed that patients with takotsubo syndrome have persistent subtle ongoing cardiac dysfunction, and many continue to have limiting symptoms despite restoration of left ventricular ejection fraction. Moreover, these patients have a substantial burden of morbidity and mortality, as well, with high rates of subsequent major adverse cardiovascular events that approach those of patients with acute coronary syndrome. The mechanisms behind this condition remain elusive. Despite substantial research, the medical community continues to have an incomplete understanding of its underlying pathogenesis and pathophysiology. Catecholamine-induced myocardial injury is the most established and well-known theory, but this does not explain all the clinical features and presentations of the condition, and numerous other pathways and abnormalities are emerging. Because of the poor understanding of its underlying pathophysiology, there is a lack of evidence-based interventions to treat the acute episode, to avoid recurrences, and to prevent major adverse cardiovascular events. This highlights the need for further research to gain a better understanding of the underlying pathophysiology to inform appropriate randomized controlled trials of interventions targeting the causative pathways. Only then can evidence-based management strategies be established to improve clinical outcomes of this potentially lethal condition.

Manganese-Enhanced Magnetic Resonance Imaging in Takotsubo Syndrome.

BACKGROUND: Takotsubo syndrome is an acute cardiac emergency characterized by transient left ventricular systolic dysfunction typically following a stressful event. Despite its rapidly rising incidence, its pathophysiology remains poorly understood. Takotsubo syndrome may pass unrecognized, especially if timely diagnostic imaging is not performed. Defective myocardial calcium homeostasis is a central cause of contractile dysfunction and has not been explored in takotsubo syndrome. We aimed to investigate myocardial calcium handling using manganese-enhanced magnetic resonance imaging during the acute and recovery phases of takotsubo syndrome. METHODS: Twenty patients with takotsubo syndrome (63±12 years of age; 90% female) and 20 volunteers matched on age, sex, and cardiovascular risk factors (59±11 years of age; 70% female) were recruited from the Edinburgh Heart Centre between March 2020 and October 2021. Patients underwent gadolinium and manganese-enhanced magnetic resonance imaging during index hospitalization with repeat manganese-enhanced magnetic resonance imaging performed after at least 3 months. RESULTS: Compared with matched control volunteers, patients had a reduced left ventricular ejection fraction (51±11 versus 67±8%; P<0.001), increased left ventricular mass (86±11 versus 57±14 g/m2; P<0.001), and, in affected myocardial segments, elevated native T1 (1358±49 versus 1211±28 ms; P<0.001) and T2 (60±7 versus 38±3 ms; P<0.0001) values at their index presentation. During manganese-enhanced imaging, kinetic modeling demonstrated a substantial reduction in myocardial manganese uptake (5.1±0.5 versus 8.2±1.1 mL/[100 g of tissue ·min], respectively; P<0.0001), consistent with markedly abnormal myocardial calcium handling. After recovery, left ejection fraction, left ventricular mass, and T2 values were comparable with those of matched control volunteers. Despite this, native and postmanganese T1 and myocardial manganese uptake remained abnormal compared with matched control volunteers (6.6±0.5 versus 8.2±1.1 mL/[100 g of tissue ·min]; P<0.0001). CONCLUSIONS: In patients with takotsubo syndrome, there is a profound perturbation of myocardial manganese uptake, which is most marked in the acute phase but persists for at least 3 months despite apparent restoration of normal left ventricular ejection fraction and resolution of myocardial edema, suggesting abnormal myocardial calcium handling may be implicated in the pathophysiology of takotsubo syndrome. Manganese-enhanced magnetic resonance imaging has major potential to assist in the diagnosis, characterization, and risk stratification of patients with takotsubo syndrome. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04623788.

Coronary Artery and Cardiac Disease in Patients With Type 2 Myocardial Infarction: A Prospective Cohort Study.

BACKGROUND: Type 2 myocardial infarction is caused by myocardial oxygen supply-demand imbalance, and its diagnosis is increasingly common with the advent of high-sensitivity cardiac troponin assays. Although this diagnosis is associated with poor outcomes, widespread uncertainty and confusion remain among clinicians as to how to investigate and manage this heterogeneous group of patients with type 2 myocardial infarction. METHODS: In a prospective cohort study, 8064 consecutive patients with increased cardiac troponin concentrations were screened to identify patients with type 2 myocardial infarction. We excluded patients with frailty or renal or hepatic failure. All study participants underwent coronary (invasive or computed tomography angiography) and cardiac (magnetic resonance or echocardiography) imaging, and the underlying causes of infarction were independently adjudicated. The primary outcome was the prevalence of coronary artery disease. RESULTS: In 100 patients with a provisional diagnosis of type 2 myocardial infarction (median age, 65 years [interquartile range, 55-74 years]; 43% women), coronary and cardiac imaging reclassified the diagnosis in 7 patients: type 1 or 4b myocardial infarction in 5 and acute myocardial injury in 2 patients. In those with type 2 myocardial infarction, median cardiac troponin I concentrations were 195 ng/L (interquartile range, 62-760 ng/L) at presentation and 1165 ng/L (interquartile range, 277-3782 ng/L) on repeat testing. The prevalence of coronary artery disease was 68% (63 of 93), which was obstructive in 30% (28 of 93). Infarct-pattern late gadolinium enhancement or regional wall motion abnormalities were observed in 42% (39 of 93), and left ventricular systolic dysfunction was seen in 34% (32 of 93). Only 10 patients had both normal coronary and normal cardiac imaging. Coronary artery disease and left ventricular systolic dysfunction were previously unrecognized in 60% (38 of 63) and 84% (27 of 32), respectively, with only 33% (21 of 63) and 19% (6 of 32) on evidence-based treatments. CONCLUSIONS: Systematic coronary and cardiac imaging of patients with type 2 myocardial infarction identified coronary artery disease in two-thirds and left ventricular systolic dysfunction in one-third of patients. Unrecognized and untreated coronary or cardiac disease is seen in most patients with type 2 myocardial infarction, presenting opportunities for initiation of evidence-based treatments with major potential to improve clinical outcomes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03338504.

Manganese-Enhanced Magnetic Resonance Imaging of the Heart.

Manganese-based contrast media were the first in vivo paramagnetic agents to be used in magnetic resonance imaging (MRI). The uniqueness of manganese lies in its biological function as a calcium channel analog, thus behaving as an intracellular contrast agent. Manganese ions are taken up by voltage-gated calcium channels in viable tissues, such as the liver, pancreas, kidneys, and heart, in response to active calcium-dependent cellular processes. Manganese-enhanced magnetic resonance imaging (MEMRI) has therefore been used as a surrogate marker for cellular calcium handling and interest in its potential clinical applications has recently re-emerged, especially in relation to assessing cellular viability and myocardial function. Calcium homeostasis is central to myocardial contraction and dysfunction of myocardial calcium handling is present in various cardiac pathologies. Recent studies have demonstrated that MEMRI can detect the presence of abnormal myocardial calcium handling in patients with myocardial infarction, providing clear demarcation between the infarcted and viable myocardium. Furthermore, it can provide more subtle assessments of abnormal myocardial calcium handling in patients with cardiomyopathies and being excluded from areas of nonviable cardiomyocytes and severe fibrosis. As such, MEMRI offers exciting potential to improve cardiac diagnoses and provide a noninvasive measure of myocardial function and contractility. This could be an invaluable tool for the assessment of both ischemic and nonischemic cardiomyopathies as well as providing a measure of functional myocardial recovery, an accurate prediction of disease progression and a method of monitoring treatment response. EVIDENCE LEVEL: 5: TECHNICAL EFFICACY: STAGE 5.

Non-invasive imaging of functional pancreatic islet beta-cell mass in people with type 1 diabetes mellitus.

AIMS: To investigate whether manganese-enhanced magnetic resonance imaging can assess functional pancreatic beta-cell mass in people with type 1 diabetes mellitus. METHODS: In a prospective case-control study, 20 people with type 1 diabetes mellitus (10 with low (≥50 pmol/L) and 10 with very low (<50 pmol/L) C-peptide concentrations) and 15 healthy volunteers underwent manganese-enhanced magnetic resonance imaging of the pancreas following an oral glucose load. Scan-rescan reproducibility was performed in 10 participants. RESULTS: Mean pancreatic manganese uptake was 31 ± 6 mL/100 g of tissue/min in healthy volunteers (median 32 [interquartile range 23-36] years, 6 women), falling to 23 ± 4 and 13 ± 5 mL/100 g of tissue/min (p ≤ 0.002 for both) in people with type1 diabetes mellitus (52 [44-61] years, 6 women) and low or very low plasma C-peptide concentrations respectively. Pancreatic manganese uptake correlated strongly with plasma C-peptide concentrations in people with type1 diabetes mellitus (r = 0.73, p < 0.001) but not in healthy volunteers (r = -0.054, p = 0.880). There were no statistically significant correlations between manganese uptake and age, body-mass index, or glycated haemoglobin. There was strong intra-observer (mean difference: 0.31 (limits of agreement -1.42 to 2.05) mL/100 g of tissue/min; intra-class correlation, ICC = 0.99), inter-observer (-1.23 (-5.74 to 3.27) mL/100 g of tissue/min; ICC = 0.85) and scan-rescan (-0.72 (-2.9 to 1.6) mL/100 g of tissue/min; ICC = 0.96) agreement for pancreatic manganese uptake. CONCLUSIONS: Manganese-enhanced magnetic resonance imaging provides a potential reproducible non-invasive measure of functional beta-cell mass in people with type 1 diabetes mellitus. This holds major promise for investigating type 1 diabetes, monitoring disease progression and assessing novel immunomodulatory interventions.

Exercise electrocardiography for pre-test assessment of the likelihood of coronary artery disease.

OBJECTIVES: To develop a tool including exercise electrocardiography (ExECG) for patient-specific clinical likelihood estimation of patients with suspected obstructive coronary artery disease (CAD). METHODS: An ExECG-weighted clinical likelihood (ExECG-CL) model was developed in a training cohort of patients with suspected obstructive CAD undergoing ExECG. Next, the ExECG-CL model was applied in a CAD validation cohort undergoing ExECG and clinically driven invasive coronary angiography and a prognosis validation cohort and compared with the risk factor-weighted clinical likelihood (RF-CL) model for obstructive CAD discrimination and prognostication, respectively.In the CAD validation cohort, obstructive CAD was defined as >50% diameter stenosis on invasive coronary angiography. For prognosis, the endpoint was non-fatal myocardial infarction and death. RESULTS: The training cohort consisted of 1214 patients (mean age 57 years, 57% males). In the CAD (N=408; mean age 55 years, 53% males) and prognosis validation (N=3283; mean age 57 years, 57% males) cohorts, 11.8% patients had obstructive CAD and 4.4% met the endpoint. In the CAD validation cohort, discrimination of obstructive CAD was similar between the ExECG-CL and RF-CL models: area under the receiver-operating characteristic curves 83.1% (95% CIs 77.5% to 88.7%) versus 80.7% (95% CI 74.6% to 86.8%), p=0.14. In the ExECG-CL model, more patients had very low (≤5%) clinical likelihood of obstructive CAD compared with the RF-CL (42.2% vs 36.0%, p<0.01) where obstructive CAD prevalence and event risk remained low. CONCLUSIONS: ExECG incorporated into a clinical likelihood model improves reclassification of patients to a very low clinical likelihood group with very low prevalence of obstructive CAD and favourable prognosis.

Modeling Robotic-Assisted Mechanical Thrombectomy Procedures with the CorPath GRX Robot: The Core-Flow Study.

BACKGROUND AND PURPOSE: Endovascular robotic devices may enable experienced neurointerventionalists to remotely perform endovascular thrombectomy. This study aimed to assess the feasibility, safety, and efficacy of robot-assisted endovascular thrombectomy compared with manual procedures by operators with varying levels of experience, using a 3D printed neurovascular model. MATERIALS AND METHODS: M1 MCA occlusions were simulated in a 3D printed neurovascular model, linked to a CorPath GRX robot in a biplane angiography suite. Four interventionalists performed manual endovascular thrombectomy (n = 45) and robot-assisted endovascular thrombectomy (n = 37) procedures. The outcomes included first-pass recanalization (TICI 2c-3), the number and size of generated distal emboli, and procedural length. RESULTS: A total of 82 experimental endovascular thrombectomies were conducted. A nonsignificant trend favoring the robot-assisted endovascular thrombectomy was observed in terms of final recanalization (89.2% versus manual endovascular thrombectomy, 71.1%; P = .083). There were no differences in total mean emboli count (16.54 [SD, 15.15] versus 15.16 [SD, 16.43]; P = .303). However, a higher mean count of emboli of > 1 mm was observed in the robot-assisted endovascular thrombectomy group (1.08 [SD, 1.00] versus 0.49 [SD, 0.84]; P = .001) compared with manual endovascular thrombectomy. The mean procedural length was longer in robot-assisted endovascular thrombectomy (6.43 [SD, 1.71] minutes versus 3.98 [SD, 1.84] minutes; P < .001). Among established neurointerventionalists, previous experience with robotic procedures did not influence recanalization (95.8% were considered experienced; 76.9% were considered novices; P = .225). CONCLUSIONS: In a 3D printed neurovascular model, robot-assisted endovascular thrombectomy has the potential to achieve recanalization rates comparable with those of manual endovascular thrombectomy within competitive procedural times. Optimization of the procedural setup is still required before implementation in clinical practice.

Rist Guide Catheter for Endovascular Procedures: Initial Case Series from a Single Center.

BACKGROUND: The transradial approach (TRA) for endovascular procedures has become a frequent practice in neurointervention. Advantages of the TRA include less access-site complications, early ambulation, and less postprocedural pain. The Rist 079 radial access guide catheter (Medtronic) is the first device designed specifically for neurointerventions performed through the TRA. In this study, we report our initial experience with the Rist catheter in a variety of neurointerventional procedures, aiming to evaluate the performance of this device and discuss its limitations. METHODS: A prospectively maintained database was retrospectively searched to identify patients who underwent procedures using the Rist catheter. Information on demographics, procedural details, and complications was recorded. RESULTS: Seventy-eight patients were included in the study, with a mean age of 60.3 years (range, 25-92 years); 45 (57.7%) were men. The interventional or diagnostic procedure was successfully completed in 77 patients (98.7%). The radial artery was the primary access-site choice in 71 patients (91%). The most frequent type of procedures performed were coiling or stent-assisted coiling (16.7%) and angioplasty and stenting (16.7%), followed by middle meningeal artery embolization (14.1%). Crossover to femoral artery access while maintaining use of the Rist was done in 5 cases (6.4%). Reasons for access or procedural failure included anatomical anomaly of the target vessel, unfavorable geometry of the great vessels, and proximal tortuosity of the supra-aortic vessels. CONCLUSION: We demonstrated a high success rate with use of the Rist catheter system for a variety of procedures.

Emerging molecular imaging targets and tools for myocardial fibrosis detection.

Myocardial fibrosis is the heart's common healing response to injury. While initially seeking to optimize the strength of diseased tissue, fibrosis can become maladaptive, producing stiff poorly functioning and pro-arrhythmic myocardium. Different patterns of fibrosis are associated with different myocardial disease states, but the presence and quantity of fibrosis largely confer adverse prognosis. Current imaging techniques can assess the extent and pattern of myocardial scarring, but lack specificity and detect the presence of established fibrosis when the window to modify this process may have ended. For the first time, novel molecular imaging methods, including gallium-68 (68Ga)-fibroblast activation protein inhibitor positron emission tomography (68Ga-FAPI PET), may permit highly specific imaging of fibrosis activity. These approaches may facilitate earlier fibrosis detection, differentiation of active vs. end-stage disease, and assessment of both disease progression and treatment-response thereby improving patient care and clinical outcomes.

Pneumothorax, pneumomediastinum, and subcutaneous emphysema in hospitalized COVID-19 patients: incidence, clinical characteristics, and outcomes.

BACKGROUND: Limited data is available on the incidence and outcomes of pneumothorax (PTX), pneumomediastinum (PNM), and subcutaneous emphysema (SCE) in COVID-19 patients. This study aimed to investigate the characteristics of these complications in hospitalized COVID-19 patients. RESEARCH DESIGN AND METHODS: A retrospective study was conducted, involving adult COVID-19 patients admitted to Mayo Clinic Florida from 03/2020-06/2022. Patients were divided into two groups based on the presence or absence of PTX/PNM/SCE. RESULTS: 1926 hospitalized patients with COVID-19 were included, of which 518 were admitted to the ICU. The incidence of PTX/PNM/SCE was 6.3%. Patients with these complications were more likely to be male, Asian, and unvaccinated. Conversely, they were less likely to have chronic obstructive pulmonary disease. Patients who developed PTX/PNM/SCE after 72 hours of admission were more likely to receive high-dose corticosteroids and for an extended duration. The affected group had an adjusted odds ratio for in-hospital mortality of 13.32 (95%CI, 8.19-21.59) and ICU admission of 9.14 (95%CI, 5.3-12.78) compared to the unaffected group. CONCLUSION: Although the occurrence of PTX/PNM/SCE in hospitalized COVID-19 patients was rare, it was associated with worse outcomes. Corticosteroids may contribute to the pathogenesis of these complications; however, further studies are needed to investigate this relationship in more detail.

Computed tomography coronary angiography in non-ST-segment elevation myocardial infarction.

Electrocardiography and high-sensitivity cardiac troponin testing are routinely applied as the initial step for clinical evaluation of patients with suspected non-ST-segment elevation myocardial infarction. Once diagnosed, patients with non-ST-segment elevation myocardial infarction are commenced on antithrombotic and secondary preventative therapies before undergoing invasive coronary angiography to determine the strategy of coronary revascularisation. However, this clinical pathway is imperfect and can lead to challenges in the diagnosis, management, and clinical outcomes of these patients. Computed tomography coronary angiography (CTCA) has increasingly been utilised in the setting of patients with suspected non-ST-segment elevation myocardial infarction, where it has an important role in avoiding unnecessary invasive coronary angiography and reducing downstream non-invasive functional testing for myocardial ischaemia. CTCA is an excellent gatekeeper for the cardiac catheterisation laboratory. In addition, CTCA provides complementary information for patients with myocardial infarction in the absence of obstructive coronary artery disease and highlights alternative or incidental diagnoses for those with cardiac troponin elevation. However, the routine application of CTCA has yet to demonstrate an impact on subsequent major adverse cardiovascular events. There are several ongoing studies evaluating CTCA and its associated technologies that will define and potentially expand its application in patients with suspected or diagnosed non-ST-segment elevation myocardial infarction. We here review the current evidence relating to the clinical application of CTCA in patients with non-ST-segment elevation myocardial infarction and highlight the areas where CTCA is likely to have an increasing important role and impact for our patients.

Does Insufficient Sleep Increase the Risk of Developing Insulin Resistance: A Systematic Review.

It has been recommended that adults sleep a minimum of seven hours of sleep every night to maintain holistic health and well-being. A considerable fraction of the adult population suffers from sleep deprivation and related disorders. The stress of modern-day living may be the cause of this curtailment of sleep duration. The primary purpose of this study was to investigate the effects of reduced sleep on the development of insulin resistance and explore the possible mechanisms linking the two. We utilized databases like such as PubMed, PubMed Central (PMC), and Medical Literature Analysis and Retrieval System Online (MEDLINE) to systematically screen papers using keywords and Medical Subject Heading (MeSH) terms. A few articles were also retrieved from Cochrane Library. We applied inclusion/exclusion criteria after screening papers via title and abstracts. A quality appraisal check was doneperformed, and ten 10 related studies were strictly reviewed. Short sleep duration was significantly associated with insulin resistance. Inflammatory markers such as C-reactive protein (CRP) and serum amyloid A (SAA), biomarkers such as glucagon-like peptide-1 (GLP-1), and circadian misalignment may play a significant role in the pathogenesis of this association. To prevent metabolic complications such as type- 2 diabetes, adequate sleep (more than seven hours per night) is required in the adult population. The causal relationship between sleep deprivation and insulin resistance is multifactorial, and further studies are warranted to understand these mechanisms better.

The Efficacy of Marijuana Use for Pain Relief in Adults With Sickle Cell Disease: A Systematic Review.

Sickle Cell Disease (SCD) is a disease that affects many around the world and often accounts for frequent hospital admissions every year, secondary to uncontrolled pain. Marijuana is increasingly being used for its medicinal ability to treat pain in chronic medical conditions. Therefore, it is imperative to determine how effective it would be in providing pain relief to patients with SCD. We systematically screened five databases for relevant data: PubMed, Medline, PubMed Central (PMC), Cochrane Library, and Google Scholar. The inclusion and exclusion criteria were implemented. A quality appraisal was then done using the Cochrane Bias assessment for randomized controlled trials (RCTs), Newcastle-Ottawa tool for observational studies, and Scale for the Assessment of Narrative Review Articles (SANRA) checklist for traditional review articles. From seven articles, information was gathered; one systematic review, one RCT, two surveys, one cross-sectional study, one retrospective study, and one questionnaire-based study. Our review concluded that based on the literature assessed, marijuana use in SCD patients either worsened their painful crises or offered little to no help compared to opioids or hydroxyurea usage. There were limited RCTs published in addition to papers investigating the long-term effects of marijuana use in SCD. We hope that further data is gathered in these areas to sufficiently address whether cannabis use is efficacious for pain relief in patients with SCD.

A Systematic Review and Meta-Analysis of the Efficacy of Buddy Taping Versus Reduction and Casting for Non-operative Management of Closed Fifth Metacarpal Neck Fractures.

A closed fifth metacarpal neck fracture is a frequently encountered upper limb fracture that occurs when the bone breaks right below the little finger's knuckle. At the moment, there is no agreement on the best way to treat these fractures. This research seeks to look at the efficacy of buddy taping versus reduction and casting for non-operative management of uncomplicated closed fifth metacarpal neck fractures. A systematic review of PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), PubMed Central (PMC), and the Cochrane Library databases was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to find relevant studies about buddy taping versus reduction and casting for non-operative management. Disabilities of the arm, shoulder, and hand (DASH) score; satisfaction score; visual analog scale (VAS); range of motion (ROM); strength; and other outcomes were reported in this study. We used Review Manager 5.4 (The Cochrane Collaboration, London, UK) for the meta-analysis. Seven trials with a total of 454 patients were considered in the review and four in the quantitative analysis. All the included studies were randomized controlled trials (RCTs). Our study concluded that buddy taping was effective for improving pain, range of motion, and strength. The DASH score and satisfaction score didn't show any significant difference. Thus, we recommend the use of buddy taping rather than plaster and immobilization for the management of uncomplicated closed fifth metacarpal neck fractures.

MRI and CT coronary angiography in survivors of COVID-19.

OBJECTIVES: To determine the contribution of comorbidities on the reported widespread myocardial abnormalities in patients with recent COVID-19. METHODS: In a prospective two-centre observational study, patients hospitalised with confirmed COVID-19 underwent gadolinium and manganese-enhanced MRI and CT coronary angiography (CTCA). They were compared with healthy and comorbidity-matched volunteers after blinded analysis. RESULTS: In 52 patients (median age: 54 (IQR 51-57) years, 39 males) who recovered from COVID-19, one-third (n=15, 29%) were admitted to intensive care and a fifth (n=11, 21%) were ventilated. Twenty-three patients underwent CTCA, with one-third having underlying coronary artery disease (n=8, 35%). Compared with younger healthy volunteers (n=10), patients demonstrated reduced left (ejection fraction (EF): 57.4±11.1 (95% CI 54.0 to 60.1) versus 66.3±5 (95 CI 62.4 to 69.8)%; p=0.02) and right (EF: 51.7±9.1 (95% CI 53.9 to 60.1) vs 60.5±4.9 (95% CI 57.1 to 63.2)%; p≤0.0001) ventricular systolic function with elevated native T1 values (1225±46 (95% CI 1205 to 1240) vs 1197±30 (95% CI 1178 to 1216) ms;p=0.04) and extracellular volume fraction (ECV) (31±4 (95% CI 29.6 to 32.1) vs 24±3 (95% CI 22.4 to 26.4)%; p<0.0003) but reduced myocardial manganese uptake (6.9±0.9 (95% CI 6.5 to 7.3) vs 7.9±1.2 (95% CI 7.4 to 8.5) mL/100 g/min; p=0.01). Compared with comorbidity-matched volunteers (n=26), patients had preserved left ventricular function but reduced right ventricular systolic function (EF: 51.7±9.1 (95% CI 53.9 to 60.1) vs 59.3±4.9 (95% CI 51.0 to 66.5)%; p=0.0005) with comparable native T1 values (1225±46 (95% CI 1205 to 1240) vs 1227±51 (95% CI 1208 to 1246) ms; p=0.99), ECV (31±4 (95% CI 29.6 to 32.1) vs 29±5 (95% CI 27.0 to 31.2)%; p=0.35), presence of late gadolinium enhancement and manganese uptake. These findings remained irrespective of COVID-19 disease severity, presence of myocardial injury or ongoing symptoms. CONCLUSIONS: Patients demonstrate right but not left ventricular dysfunction. Previous reports of left ventricular myocardial abnormalities following COVID-19 may reflect pre-existing comorbidities. TRIAL REGISTRATION NUMBER: NCT04625075.

Sodium-glucose co-transporter 2 inhibitor therapy: mechanisms of action in heart failure.

Patients with type 2 diabetes mellitus are at a higher risk of developing heart failure compared with the healthy population. In recent landmark clinical trials, sodium-glucose co-transporter 2 (SGLT2) inhibitor therapies improve blood glucose control and also reduce cardiovascular events and heart failure hospitalisations in patients with type 2 diabetes. Intriguingly, such clinical benefits have also been seen in patients with heart failure in the absence of type 2 diabetes although the underlying mechanisms are not clearly understood. Potential pathways include improved glycaemic control, diuresis, weight reduction and reduction in blood pressure, but none fully explain the observed improvements in clinical outcomes. More recently, novel mechanisms have been proposed to explain these benefits that include improved cardiomyocyte calcium handling, enhanced myocardial energetics, induced autophagy and reduced epicardial fat. We provide an up-to-date review of cardiac-specific SGLT2 inhibitor-mediated mechanisms and highlight studies currently underway investigating some of the proposed mechanisms of action in cardiovascular health and disease.

MINOCA: a heterogenous group of conditions associated with myocardial damage.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) was first described over 80 years ago. The term has been widely and inconsistently used in clinical practice, influencing various aspects of disease classification, investigation and management. MINOCA encompasses a heterogenous group of conditions that include both atherosclerotic and non-atherosclerotic disease resulting in myocardial damage that is not due to obstructive coronary artery disease. In many ways, it is a term that describes a moment in the diagnostic pathway of the patient and is arguably not a diagnosis. Central to the definition is also the distinction between myocardial infarction and injury. The universal definition of myocardial infarction distinguishes acute myocardial infarction, including those with MINOCA, from other causes of myocardial injury by the presence of clinical evidence of ischaemia. However, these ischaemic features are often non-specific causing diagnostic confusion, and can create difficulties for patient management and follow-up. The purpose of this review is to summarise our current understanding of MINOCA and highlight important issues relating to the diagnosis, investigation and management of patients with MINOCA.