Prognostic Value of Stress Perfusion Cardiac MRI in Cardiovascular Disease: A Systematic Review and Meta-Analysis of the Effects of the Scanner, Stress Agent, and Analysis Technique.

Purpose To perform a systematic review and meta-analysis to assess the prognostic value of stress perfusion cardiac MRI in predicting cardiovascular outcomes. Materials and Methods A systematic literature search from the inception of PubMed, Embase, Web of Science, and China National Knowledge Infrastructure until January 2023 was performed for articles that reported the prognosis of stress perfusion cardiac MRI in predicting cardiovascular outcomes. The quality of included studies was assessed using the Quality in Prognosis Studies tool. Reported hazard ratios (HRs) of univariable regression analyses with 95% CIs were pooled. Comparisons were performed across different analysis techniques (qualitative, semiquantitative, and fully quantitative), magnetic field strengths (1.5 T vs 3 T), and stress agents (dobutamine, adenosine, and dipyridamole). Results Thirty-eight studies with 58 774 patients with a mean follow-up time of 53 months were included. There were 1.9 all-cause deaths and 3.5 major adverse cardiovascular events (MACE) per 100 patient-years. Stress-inducible ischemia was associated with a higher risk of all-cause mortality (HR: 2.55 [95% CI: 1.89, 3.43]) and MACE (HR: 3.90 [95% CI: 2.69, 5.66]). For MACE, pooled HRs of qualitative, semiquantitative, and fully quantitative methods were 4.56 (95% CI: 2.88, 7.22), 3.22 (95% CI: 1.60, 6.48), and 1.78 (95% CI: 1.39, 2.28), respectively. For all-cause mortality, there was no evidence of a difference between qualitative and fully quantitative methods (P = .79). Abnormal stress perfusion cardiac MRI findings remained prognostic when subgrouped based on underlying disease, stress agent, and field strength, with HRs of 3.54, 2.20, and 3.38, respectively, for all-cause mortality and 3.98, 3.56, and 4.21, respectively, for MACE. There was no evidence of subgroup differences in prognosis between field strengths or stress agents. There was significant heterogeneity in effect size for MACE outcomes in the subgroups assessing qualitative versus quantitative stress perfusion analysis, underlying disease, and field strength. Conclusion Stress perfusion cardiac MRI is valuable for predicting cardiovascular outcomes, regardless of the analysis method, stress agent, or magnetic field strength used. Keywords: MR-Perfusion, MRI, Cardiac, Meta-Analysis, Stress Perfusion, Cardiac MR, Cardiovascular Disease, Prognosis, Quantitative © RSNA, 2024 Supplemental material is available for this article.

Co-localization of the sodium-glucose co-transporter-2 channel (SGLT-2) with endothelin ETA and ETB receptors in human cardiorenal tissue.

Endothelin (ET) receptor antagonists are being investigated in combination with sodium-glucose co-transporter-2 inhibitors (SGLT-2i). These drugs primarily inhibit the SGLT-2 transporter that, in humans, is thought to be mainly restricted to the renal proximal convoluted tubule, resulting in increased glucose excretion favouring improved glycaemic control and diuresis. This action reduces fluid retention with ET receptor antagonists. Studies have suggested SGLT-2 may also be expressed in cardiomyocytes of human heart. To understand the potential of combining the two classes of drugs, our aim was to compare the distribution of ET receptor sub-types in human kidney, with SGLT-2. Secondly, using the same experimental conditions, we determined if SGLT-2 expression could be detected in human heart and whether the transporter co-localised with ET receptors. METHODS: Immunocytochemistry localised SGLT-2, ETA and ETB receptors in sections of histologically normal kidney, left ventricle from patients undergoing heart transplantation or controls. Primary antisera were visualised using fluorescent microscopy. Image analysis was used to measure intensity compared with background in adjacent control sections. RESULTS: As expected, SGLT-2 localised to epithelial cells of the proximal convoluted tubules, and co-localised with both ET receptor sub-types. Similarly, ETA receptors predominated in cardiomyocytes; low (compared with kidney but above background) positive staining was also detected for SGLT-2. DISCUSSION: Whether low levels of SGLT-2 have a (patho)physiological role in cardiomyocytes is not known but results suggest the effect of direct blockade of sodium (and glucose) influx via SGLT-2 inhibition in cardiomyocytes should be explored, with potential for additive effects with ETA antagonists.

Simultaneous Liver Kidney Transplantation in a Primary Type 2 Hyperoxaluria With Corrected TOF and Severe Cardiomyopathy: A Case Report.

Background: Primary type 2 hyperoxaluria is a very rare genetic disorder,1,2 where in the progression to renal failure was assumed to be insidious and not very common.3 PH2 is due to deficient glyoxylate reductase/hydroxypyruvate reductase (GRHPR),1,2 which was thought to have extra-hepatic production also.4 The progression to renal failure in these patient subgroups is well documented in the Literature and the role of SLK (simultaneous liver and kidney transplantation) has not been clearly established.8. Method: We present a case report of a young girl with PH2, who successfully underwent SLK, with evidence of reduction in the urine oxalate levels post SLK. Results: PH2, though a rare genetic disease, has a proven potential to progress to chronic renal failure requiring transplantation, renal transplantation alone has not shown any benefit, these patients can be offered SLK as a primary treatment option, to improve the outcomes, this needs further validation with consensus and studies.

Subtle Visual Latency Can Profoundly Impair Implicit Sensorimotor Learning.

Short sub-100ms visual feedback latencies are common in many types of human-computer interactions yet are known to markedly reduce performance in a wide variety of motor tasks from simple pointing to operating surgical robotics. These latencies are also present in the computer-based experiments used to study the sensorimotor learning that underlies the acquisition of motor performance. Inspired by neurophysiological findings showing that cerebellar LTD and cortical LTP would both be disrupted by sub-100ms latencies, we hypothesized that implicit sensorimotor learning may be particularly sensitive to these short latencies. Remarkably, we find that improving latency by just 60ms, from 85 to 25ms in latency-optimized experiments, increases implicit learning by 50% and proportionally decreases explicit learning, resulting in a dramatic reorganization of sensorimotor memory. We go on to show that implicit sensorimotor learning is considerably more sensitive to latencies in the sub-100ms range than at higher latencies, in line with the latency-specific neural plasticity that has been observed. This suggests a clear benefit for latency reduction in computer-based training that involves implicit sensorimotor learning and that across-study differences in implicit motor learning might often be explained by disparities in feedback latency.

An enhanced IL17 and muted type I interferon nasal epithelial cell state characterizes severe COVID-19 with fungal coinfection.

Recent case reports and epidemiological data suggest that fungal infections represent an underappreciated complication among people with severe COVID-19. However, the frequency of fungal colonization in patients with COVID-19 and associations with specific immune responses in the airways remain incompletely defined. We previously generated a single-cell RNA-sequencing data set characterizing the upper respiratory microenvironment during COVID-19 and mapped the relationship between disease severity and the local behavior of nasal epithelial cells and infiltrating immune cells. Our previous study, in agreement with findings from related human cohorts, demonstrated that a profound deficiency in host immunity, particularly in type I and type III interferon signaling in the upper respiratory tract, is associated with rapid progression to severe disease and worse clinical outcomes. We have now performed further analysis of this cohort and identified a subset of participants with severe COVID-19 and concurrent detection of Candida species-derived transcripts within samples collected from the nasopharynx and trachea. Here, we present the clinical characteristics of these individuals. Using matched single-cell transcriptomic profiles of these individuals' respiratory mucosa, we identify epithelial immune signatures suggestive of IL17 stimulation and anti-fungal immunity. Further, we observe a significant expression of anti-fungal inflammatory cascades in the nasal and tracheal epithelium of all participants who went on to develop severe COVID-19, even among participants without detectable genetic material from fungal pathogens. Together, our data suggest that IL17 stimulation-in part driven by Candida colonization-and blunted interferon signaling represent a common feature of severe COVID-19 infection. IMPORTANCE: In this paper, we present an analysis suggesting that symptomatic and asymptomatic fungal coinfections can impact patient disease progression during COVID-19 hospitalization. By looking into the presence of other pathogens and their effect on the host immune response during COVID-19 hospitalizations, we aim to offer insight into an underestimated scenario, furthering our current knowledge of determinants of severity that could be considered for future diagnostic and intervention strategies.

Phase 3 RCT comparing docetaxel-platinum with docetaxel-platinum-5FU as neoadjuvant chemotherapy in borderline resectable oral cancer.

BACKGROUND: Neoadjuvant chemotherapy (NACT) with TPF (docetaxel, cisplatin, and 5FU) is one of the treatment options in very locally advanced oral cancer with a survival advantage over PF (cisplatin and 5FU). TP (docetaxel and cisplatin) has shown promising results with a lower rate of adverse events but has never been compared to TPF. METHODS: In this phase 3 randomized superiority study, adult patients with borderline resectable locally advanced oral cancers were randomized in a 1:1 fashion to either TP or TPF. After the administration of 2 cycles, patients were evaluated in a multidisciplinary clinic and further treatment was planned. The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and adverse events. RESULTS: 495 patients were randomized in this study, 248 patients in TP arm and 247 in TPF arm. The 5-year OS was 18.5% (95% CI 13.8-23.7) and 23.9% (95% CI 18.1-30.1) in TP and TPF arms, respectively (Hazard ratio 0.778; 95% CI 0.637-0.952; P = 0.015). Following NACT, 43.8% were deemed resectable, but 34.5% underwent surgery. The 5-year OS was 50.7% (95% CI 41.5-59.1) and 5% (95%CI 2.9-8.1), respectively, in the surgically resected versus unresected cohort post NACT (P < 0.0001). Grade 3 or above adverse events were seen in 97 (39.1%) and 179 (72.5%) patients in the TP and TPF arms, respectively (P < 0.0001). CONCLUSION: NACT with TPF has a survival benefit over TP in borderline resectable oral cancers, with an increase in toxicity which is manageable. Patients who undergo surgery achieve a relatively good, sustained survival.

Case-control analysis of venous thromboembolism risk in non-alcoholic steatohepatitis diagnosed by transient elastography.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Studies have shown a strong association between non-alcoholic steatohepatitis (NASH) cirrhosis and portal vein thrombosis. Specifically, there is paucity of data on the association of NASH and venous thromboembolism (VTE), with one such study predicting a 2.5-fold increased risk for VTE compared to other liver diseases in hospitalized patients. The mechanism is believed to be a hepatocellular injury, which causes a chronic inflammatory state leading to the unregulated activation of procoagulant factors. There has been no prior analysis of the degree of steatosis and fibrosis (measured using transient elastography, commonly known as FibroScan) in NASH and its association with VTE. AIM: To examine the association between the degree of hepatic steatosis and fibrosis, quantified by transient elastography, and the incidence of VTE in patients with NASH. METHODS: In our case-control study, we included patients with a documented diagnosis of NASH. We excluded patients with inherited thrombophilia, hemoglobinopathy, malignancy, alcohol use disorder, autoimmune hepatitis, and primary biliary cirrhosis. The collected data included age, demographics, tobacco use, recreational drug use, medical history, and vibration controlled transient elastography scores. VTE-specific data included the location, type of anticoagulant, need for hospital stay, and history of VTE recurrence. Steatosis was categorized as S0-S1 (mild) and S2-S3 (moderate to severe) based on the controlled attenuation parameter score. Fibrosis was classified based on the kilopascal score and graded as F0-F1 (Metavir stage), F2, F3, and F4 (cirrhosis). χ2 and Mann-Whitney U tests were used for the qualitative and quantitative variable analyses, respectively. Furthermore, we performed a logistic regression using VTE as the dependent variable. RESULTS: A total of 415 patients were analyzed, and 386 met the inclusion criteria. 51 and 335 patients were included in the VTE and non-VTE groups, respectively. Patients with VTE had a mean age of 60.63 years compared to 55.22 years in the non-VTE group (P < 0.014). Patients with VTE had a higher body mass index (31.14 kg/m² vs 29.30 kg/m²) and a higher prevalence of diabetes mellitus (29.4% vs 13.1%). The history of NASH was significantly higher in the VTE group (45.1% vs 30.4%, P < 0.037). Furthermore, moderate-to-severe steatosis was significantly higher in the VTE group (66.7% vs 47.2%, P < 0.009). Similarly, the F2-F4 fibrosis grade had a prevalence of 58.8% in the VTE group compared to 38.5% in the non-VTE group (P < 0.006). On logistic regression, using VTE as a dependent variable, diabetes mellitus had an odds ratio (OR) =1.702 (P < 0.015), and F2-F4 fibrosis grade had an OR = 1.5 (P < 0.033). CONCLUSION: Our analysis shows that NASH is an independent risk factor for VTE, especially deep vein thrombosis. There was a statistically significant association between the incidence of VTE, moderate-to-severe steatosis, and fibrosis. All hospitalized patients should be considered for medical thromboprophylaxis, particularly those with NASH.

The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.16177. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Computer-aided design software-enabled preclinical prosthodontic training: A digital education technique.

The prosthodontics preclinical training modules involve textbook-based two-dimensional (2D) ideal images and practicing on manikin models to emulate ideal tooth preparations and teeth arrangements. Relying solely on 2D images as objectives for preclinical exercises limits the trainee's creative skills to instructions of textbooks and clinical instructions received. With advancements in digital dentistry, dental trainees should have early exposure to the three-dimensional (3D) rendering of ideal preclinical objectives. A dental education technique using computer-aided design software and smartphones is described that will allow 3D rendering of ideal prosthodontic training assignments allowing early exposure to digital dentistry for dental training students.

Semantic segmentation of plant roots from RGB (mini-) rhizotron images-generalisation potential and false positives of established methods and advanced deep-learning models.

BACKGROUND: Manual analysis of (mini-)rhizotron (MR) images is tedious. Several methods have been proposed for semantic root segmentation based on homogeneous, single-source MR datasets. Recent advances in deep learning (DL) have enabled automated feature extraction, but comparisons of segmentation accuracy, false positives and transferability are virtually lacking. Here we compare six state-of-the-art methods and propose two improved DL models for semantic root segmentation using a large MR dataset with and without augmented data. We determine the performance of the methods on a homogeneous maize dataset, and a mixed dataset of > 8 species (mixtures), 6 soil types and 4 imaging systems. The generalisation potential of the derived DL models is determined on a distinct, unseen dataset. RESULTS: The best performance was achieved by the U-Net models; the more complex the encoder the better the accuracy and generalisation of the model. The heterogeneous mixed MR dataset was a particularly challenging for the non-U-Net techniques. Data augmentation enhanced model performance. We demonstrated the improved performance of deep meta-architectures and feature extractors, and a reduction in the number of false positives. CONCLUSIONS: Although correction factors are still required to match human labelled root lengths, neural network architectures greatly reduce the time required to compute the root length. The more complex architectures illustrate how future improvements in root segmentation within MR images can be achieved, particularly reaching higher segmentation accuracies and model generalisation when analysing real-world datasets with artefacts-limiting the need for model retraining.

Influence of nonalcoholic fatty liver disease on inflammatory bowel disease hospitalizations in the United States.

Background: The reported prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with inflammatory bowel disease (IBD) is 32%. We assessed the influence of NAFLD on IBD hospitalizations in the United States (US). Methods: We utilized the National Inpatient Sample database, from 2016-2019, to identify the total IBD hospitalizations in the US and we further subdivided them according to the presence or absence of NAFLD. Hospitalization characteristics, comorbidities and outcomes were compared. Statistical significance was set at P<0.05. Results: There were 1,272,260 IBD hospitalizations in the US, of which 5.04% involved NAFLD. For IBD hospitalizations with NAFLD, the mean age was 50-64 years, and the proportion of males was 46.97%. IBD hospitalizations with NAFLD had a lower proportion of African Americans (8.7% vs. 11.38%, P<0.001). Comorbidities such as hypertension (50.34% vs. 44.04%, P<0.001) and obesity (18.77% vs. 11.81%, P<0.001) were significantly higher in the NAFLD cohort. Overall, based on the Charlson Comorbidity Index, patients with NAFLD had a higher number of comorbidities (52.77% vs. 20.66%, P<0.001). Mortality was higher in the NAFLD compared to the non-NAFLD cohort (3.14% vs. 1.44%, P<0.001). Patients with NAFLD also incurred significantly higher hospital charges ($69,536 vs. $55,467, p<0.001) and had a longer mean length of stay (6.10 vs. 5.27 days, P<0.001) compared to the cohort without NAFLD. Complications and inpatient procedure requirements were also higher in the NAFLD cohort. Conclusion: Our study revealed greater mortality, morbidity, and healthcare resource utilization in patients with IBD who were hospitalized with a concomitant diagnosis of NAFLD.

Outpatient Treatment of Confirmed COVID-19: Living, Rapid Practice Points From the American College of Physicians (Version 2).

DESCRIPTION: Evidence for the use of outpatient treatments in adults with confirmed COVID-19 continues to evolve with new data. This is version 2 of the American College of Physicians (ACP) living, rapid practice points focusing on 22 outpatient treatments for COVID-19, specifically addressing the dominant SARS-CoV-2 Omicron variant. METHODS: The Population Health and Medical Science Committee (formerly the Scientific Medical Policy Committee) developed this version of the living, rapid practice points on the basis of a living, rapid review done by the ACP Center for Evidence Reviews at Cochrane Austria at the University for Continuing Education Krems (Danube University Krems). This topic will be maintained as living and rapid by continually monitoring and assessing the impact of new evidence. PRACTICE POINT 1: Consider molnupiravir to treat symptomatic patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at a high risk for progressing to severe disease. PRACTICE POINT 2: Consider nirmatrelvir-ritonavir combination therapy to treat symptomatic patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at a high risk for progressing to severe disease. PRACTICE POINT 3: Do not use ivermectin to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 4: Do not use sotrovimab to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting.

Hyperglycemia in COVID-19 infection without diabetes mellitus: Association with inflammatory markers.

BACKGROUND: New onset hyperglycemia is common in patients with severe coronavirus disease 2019 (COVID-19) infection. Cytokine storm due to COVID-19 infection is an essential etiology for new-onset hyperglycemia, but factors like direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced pancreatic ß-cell failure have also been postulated to play a role. AIM: We plan to investigate further the mechanisms underlying SARS-CoV-2 infection-induced hyperglycemia, particularly the rationale of the cytokine-induced hyperglycemia hypothesis, by evaluating the association between inflammatory markers and new onset hyperglycemia in non-diabetic patients with COVID-19 infection. METHODS: We conducted a retrospective case-control study on adults without diabetes mellitus hospitalized for COVID-19 infection. The serum levels of glucose and inflammatory markers at presentation before initiation of corticosteroid were collected. Hyperglycemia was defined as glucose levels ≥ 140 mg/dL. C-Reactive protein (CRP) ≥ 100 mg/L, ferritin ≥ 530 ng/mL, lactate dehydrogenase (LDH) ≥ 590 U/L, and D-dimer ≥ 0.5 mg/L were considered elevated. We used the χ 2 test for categorical variables and the Mann-Whitney U test for continuous variables and calculated the logistic regression for hyperglycemia. RESULTS: Of the 520 patients screened, 248 met the inclusion criteria. Baseline demographics were equally distributed between patients with hyperglycemia and those who were normoglycemic. Serum inflammatory markers in patients with or without new-onset hyperglycemia were elevated as follows: CRP (58.1% vs 65.6%, P = 0.29), ferritin (48.4% vs 34.9%, P = 0.14), D-dimer (37.1% vs 37.1%, P = 0.76) and LDH (19.4% vs 11.8%, P = 0.02). Logistic regression analysis showed LDH odds ratio (OR) = 1.623 (P = 0.256). We observed significantly higher mortality (24.2% vs 9.1%, P = 0.001; OR = 2.528, P = 0.024) and length of stay (8.89 vs 6.69, P = 0.026) in patients with hyperglycemia. CONCLUSION: Our study showed no association between CRP, ferritin, LDH, D-dimer levels, and new-onset hyperglycemia in non-diabetic patients with COVID-19 infection. It also shows an increased mortality risk and length of stay in patients with hyperglycemia. With new-onset hyperglycemia being closely associated with poor prognostic indices, it becomes pivotal to understand the underlying pathophysiological mechanisms behind the SARS-CoV-2 infection-induced hyperglycemia. We conclude that the stress hyperglycemia hypothesis is not the only mechanism of SARS-CoV-2 infection-induced hyperglycemia but rather a multicausal pathogenesis leading to hyperglycemia that requires further research and understanding. This would help us improve not only the clinical outcomes of COVID-19 disease and inpatient hyperglycemia management but also understand the long-term effects of SARS-CoV-2 infection and further management.

Oral Class I and III antiarrhythmic drugs for maintaining sinus rhythm after catheter ablation of atrial fibrillation.

BACKGROUND: Recurrence of atrial tachyarrhythmias (ATa) following catheter ablation for atrial fibrillation (AF) is a common problem. Antiarrhythmic drugs have been used shortly after ablation in an attempt to maintain sinus rhythm, particularly Class I and III agents. However, it still needs to be established if the use of Class I or III antiarrhythmic medications, or both, reduce the risk of recurrence of ATa. OBJECTIVES: To assess the effects of oral Class I and III antiarrhythmic drugs versus control (standard medical therapy without Class I or III antiarrhythmics, or placebo) for maintaining sinus rhythm in people undergoing catheter ablation for AF. SEARCH METHODS: We systematically searched CENTRAL, MEDLINE, Embase, Web of Science Core Collection, and two clinical trial registers without restrictions on language or date to 5 August 2022. SELECTION CRITERIA: We sought published, unpublished, and ongoing parallel-design, randomised controlled trials (RCTs) involving adult participants undergoing ablation for AF, with subsequent comparison of Class I and/or III antiarrhythmic use versus control (standard medical therapy or non-Class I and/or III antiarrhythmic use). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane and performed meta-analyses with risk ratios (RR) and Peto odds ratios (Peto OR). Our primary outcomes were recurrence of atrial tachyarrhythmias; adverse events: thromboembolic events; adverse events: myocardial infarction; adverse events: new diagnosis of heart failure; and adverse events: requirement for one or more hospitalisations for atrial tachyarrhythmia. Our secondary outcomes were: all-cause mortality; and requirement for one or more repeat ablations. Where possible, we performed comparison analysis by Class I and/or III antiarrhythmic and divided follow-up periods for our primary outcome. We performed comprehensive assessments of risk of bias and certainty of evidence applying the GRADE methodology. MAIN RESULTS: We included nine RCTs involving a total of 3269 participants. Participants were on average 59.3 years old; 71.0% were male; and 72.9% and 27.4% had paroxysmal and persistent AF, respectively. Class I and/or III antiarrhythmics may reduce recurrence of ATa at 0 to 3 months postablation (risk ratio (RR) 0.74, 95% confidence interval (CI) 0.59 to 0.94, 8 trials, 3046 participants, low-certainty evidence) and likely reduce recurrence at > 3 to 6 months, our a priori primary time point (RR 0.85, 95% CI 0.78 to 0.93, 5 trials, 2591 participants, moderate-certainty evidence). Beyond six months the evidence is very uncertain, and the benefit of antiarrhythmics may not persist (RR 1.14, 95% CI 0.84 to 1.55, 4 trials, 2244 participants, very low-certainty evidence). The evidence suggests that Class I and/or III antiarrhythmics may not increase the risk of thromboembolic events, myocardial infarction, all-cause mortality, or requirement for repeat ablation, at 0 to 3, > 3 to 6, and > 6 months (where data were available; low- to very low-certainty evidence). The use of Class I and/or III antiarrhythmics postablation likely reduces hospitalisations for ATa by approximately 57% at 0 to 3 months (RR 0.43, 95% CI 0.28 to 0.64, moderate-certainty evidence). No data were available beyond three months. No data were available on new diagnoses of heart failure. Fewer data were available for Class I and III antiarrhythmics individually. Based on only one and two trials (n = 125 to 309), Class I antiarrhythmics may have little effect on recurrence of ATa at 0 to 3, > 3 to 6, and > 6 months (RR 0.88, 95% CI 0.64 to 1.20, 2 trials, 309 participants; RR 0.54, 95% CI 0.25 to 1.19, 1 trial, 125 participants; RR 0.87, 95% CI 0.57 to 1.32, 1 trial, 125 participants; low-certainty evidence throughout); requirement for hospitalisation for ATa at 0 to 3 months (low-certainty evidence); or requirement for repeat ablation at 0 to 3 months (low-certainty evidence). No data were available for thromboembolic events, myocardial infarction, new diagnosis of heart failure, or all-cause mortality at any time points, or hospitalisation or repeat ablation beyond three months. Class III antiarrhythmics may have little effect on recurrence of ATa at up to 3 months and at > 3 to 6 months (RR 0.76, 95% CI 0.50 to 1.16, 4 trials, 599 participants, low-certainty evidence; RR 0.82, 95% CI 0.62 to 1.09, 2 trials, 318 participants, low-certainty evidence), and beyond 6 months one trial reported a possible increase in recurrence of ATa (RR 1.95, 95% CI 1.29 to 2.94, 1 trial, 112 participants, low-certainty evidence). Class III antiarrhythmics likely reduce hospitalisations for ATa at 0 to 3 months (RR 0.40, 95% CI 0.26 to 0.63, moderate-certainty evidence), and may have little effect on all-cause mortality (low- to very low-certainty evidence). The effect of Class III antiarrhythmics on thromboembolic events and requirement for repeat ablation was uncertain (very low-certainty evidence for both outcomes). No data were available for myocardial infarction or new diagnosis of heart failure at any time point, outcomes other than recurrence beyond 6 months, or for hospitalisation and repeat ablation > 3 to 6 months. We assessed the majority of included trials as at low or unclear risk of bias. One trial reported an error in the randomisation process, raising the potential risk of selection bias; most of the included trials were non-blinded; and two trials were at high risk of attrition bias. AUTHORS' CONCLUSIONS: We found evidence to suggest that the use of Class I and/or III antiarrhythmics up to 3 months after ablation is associated with a reduced recurrence of ATa 0 to 6 months after ablation, which may not persist beyond 6 months, and an immediate reduction in hospitalisation for ATa 0 to 3 months after ablation. The evidence suggests there is no difference in rates of all-cause mortality, thromboembolic events, or myocardial infarction between Class I and/or III antiarrhythmics versus control.

A smartphone application with a gray card for clinical shade selection: A technique.

Shade selection is an inherently complex procedure, and its accurate reproduction in the definitive restoration involves an in-depth understanding of color science and its effective communication with the dental laboratory technician. A technique is presented that uses a smartphone application (Snapseed; Google LLC) and a gray card for clinical shade selection.

From ABCD to E for endothelin in resistant hypertension.

The potent vasoconstrictor peptide endothelin-1 has long been recognized as a physiological regulator of vascular tone. However, pharmacological blockade of the endothelin-1 pathway has few proven indications thus far. A recent clinical trial for resistant hypertension published in The Lancet may yet herald a new era for endothelin receptor antagonists into the clinical mainstream.

Hypertension and Severe Hypokalemia Associated With Oral Ingestion of Topical Hydrocortisone Cream.

Background: Topical use of corticosteroids causes systemic effects, but systemic toxicity by ingesting topical corticosteroid cream has not been reported. We describe a patient admitted with ingestion of over-the-counter (OTC) hydrocortisone cream. Case Report: A 64-year-old woman presented with 2-weeks of generalized weakness. She had a history of hypertension, anxiety, depression, and chronic fatigue syndrome, but medical records were unavailable and she was not on any medications. She reported taking prednisone 7.5 mg daily for several years, which was discontinued 5 months ago. Due to worsening symptoms, she started ingesting OTC topical hydrocortisone as replacement and admitted to consuming 2 squirts of 1% hydrocortisone cream twice daily over the previous month leading up to hospitalization. Her pulse rate was 77/min, blood pressure was 232/110 mmHg. There was no pedal edema, elevated jugular venous pressure, hirsutism, muscle wasting, or purplish skin striae. Labs revealed potassium 1.5 mg/dL (3.6-5.4), serum cortisol 61.5 µg/dL (2.3-19.4), Creatine Kinase 1864 IU/L (24-173), undetectable adrenocorticotropic hormone. She received potassium, labetalol, and intravenous fluids. Her serum cortisol level decreased to 11 µg/dL and potassium to 4.1 mg/dL within 24 hours. She left the hospital against medical advice on Day 2. Discussion: Although both prednisone and hydrocortisone have glucocorticoid properties, only hydrocortisone has mineralocorticoid properties. Hydrocortisone 20 mg provides a mineralocorticoid effect equivalent to 0.1 mg fludrocortisone. Conclusion: Hydrocortisone cream was confirmed as the source of exogenous corticosteroid by an undetectable adrenocorticotropic hormone and rapid decrease in cortisol following discontinuation. Incorrect use of OTC medications can lead to life-threatening side effects.

Outpatient Treatment of Confirmed COVID-19: Living, Rapid Practice Points From the American College of Physicians (Version 1).

DESCRIPTION: Strategies to manage COVID-19 in the outpatient setting continue to evolve as new data emerge on SARS-CoV-2 variants and the availability of newer treatments. The Scientific Medical Policy Committee (SMPC) of the American College of Physicians (ACP) developed these living, rapid practice points to summarize the best available evidence on the treatment of adults with confirmed COVID-19 in an outpatient setting. These practice points do not evaluate COVID-19 treatments in the inpatient setting or adjunctive COVID-19 treatments in the outpatient setting. METHODS: The SMPC developed these living, rapid practice points on the basis of a living, rapid review done by the ACP Center for Evidence Reviews at Cochrane Austria at the University for Continuing Education Krems (Danube University Krems). The SMPC will maintain these practice points as living by monitoring and assessing the impact of new evidence. PRACTICE POINT 1: Consider molnupiravir to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 to 7 days of the onset of symptoms and at high risk for progressing to severe disease. PRACTICE POINT 2: Consider nirmatrelvir-ritonavir combination therapy to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at high risk for progressing to severe disease. PRACTICE POINT 3: Consider remdesivir to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 7 days of the onset of symptoms and at high risk for progressing to severe disease. PRACTICE POINT 4: Do not use azithromycin to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 5: Do not use chloroquine or hydroxychloroquine to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 6: Do not use ivermectin to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 7: Do not use nitazoxanide to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 8: Do not use lopinavir-ritonavir combination therapy to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 9: Do not use casirivimab-imdevimab combination therapy to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting unless it is considered effective against a SARS-CoV-2 variant or subvariant locally in circulation. PRACTICE POINT 10: Do not use regdanvimab to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting unless it is considered effective against a SARS-CoV-2 variant or subvariant locally in circulation. PRACTICE POINT 11: Do not use sotrovimab to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting unless it is considered effective against a SARS-CoV-2 variant or subvariant locally in circulation. PRACTICE POINT 12: Do not use convalescent plasma to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 13: Do not use ciclesonide to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 14: Do not use fluvoxamine to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting.